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Sample records for cognitive dysfunction caused

  1. Cognitive dysfunction resulting from hippocampal hyperactivity--a possible cause of anxiety disorder?

    Science.gov (United States)

    McNaughton, N

    1997-04-01

    Pure cognition and hence pure cognitive dysfunction might be expected to have no direct relation to any specific emotion. Changes in cognitive processing will change the assessment of stimuli and thus could change emotional responses nonspecifically. However, neurology suggests a more direct relation between at least some aspects of cognition and emotion. The limbic system in general and the hippocampus in particular have been suggested at different times to be crucial for both memory and emotion. Even recently, O'Keefe and Nadel (The hippocampus as a cognitive map, Oxford University Press, 1978) proposed that the hippocampus is a spatial, or cognitive, map, while Gray (The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system. Oxford University Press, 1982) proposed that it is central to anxiety. This apparent incongruity can be resolved by combining recent developments in the psychology of anxiety (which emphasise changed processing biases), recent extensions of Gray's theory (which bring it closer to cognitive views), and recent theories of the role of the hippocampus in memory (which see it as controlling rather than storing information). This paper proposes that at least some instances of clinical anxiety could result from hyperactivity of the septo-hippocampal system, which would produce cognitive dysfunction in the form of increased negative association of stimuli with a consequential increase in anxiety when the stimuli are subsequently presented.

  2. Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia.

    Science.gov (United States)

    Cai, Mudan; Lee, Jun Hwan; Yang, Eun Jin

    2017-10-01

    Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n = 15), BCCAO control group (n = 15), and BV-treated BCCAO group (n = 15). BCCAO animals were treated with 0.1 μg/g BV at ST36 ("Joksamli" acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.

  3. Peri-operative cognitive dysfunction and protection

    DEFF Research Database (Denmark)

    Steinmetz, J; Rasmussen, L S

    2016-01-01

    Cognition may decline after surgery. Postoperative delirium, especially when hyperactive, may be easily recognised, whereas cognitive dysfunction is subtle and can only be detected using neuropsychological tests. The causes for these two conditions are largely unknown, although they share risk...... factors, the predominant one being age. Ignorance of the causes for postoperative cognitive dysfunction contributes to the difficulty of conducting interventional studies. Postoperative cognitive disorders are associated with increased mortality and permanent disability. Peri-operative interventions can...... reduce the rate of delirium in the elderly, but in spite of promising findings in animal experiments, no intervention reduces postoperative cognitive dysfunction in humans....

  4. Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

    Directory of Open Access Journals (Sweden)

    Ruixue Song

    2017-01-01

    Full Text Available Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC. Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

  5. Does anaesthesia cause postoperative cognitive dysfunction? : a randomised study of regional versus general anaesthesia in 438 elderly patients

    NARCIS (Netherlands)

    Rasmussen, L.S.; Johnson, T.; Kuipers, H.M.; Kristensen, D.; Siersma, V.D.; Vila, P.; Jolles, J.; Papaioannou, A.; Abildstrom, H.; Silverstein, J.H.; Bonal, J.A.; Raeder, J.; Nielsen, I.K.; Korttila, K.; Munoz, L.; Dodds, C.; Hanning, C.D.; Moller, J.T.

    2003-01-01

    Keywords:anesthesia;cognitive function;complications;postoperative period;regional anesthesia;surgery Background: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the

  6. Cognitive dysfunction in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Joana eGuimarães

    2012-05-01

    Full Text Available In Multiple Sclerosis (MS prevalence studies of community and clinical samples, indicate that 45–60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes particularly important. In this review the authors address: the cognitive domains most commonly impaired in MS (memory, attention, executive functions, speed of information processing and visual spatial abilities; the physiopathological mechanism implied in MS cognitive dysfunction and correlated brain MRI features; the importance of neuropsychological assessment of MS patients in different stages of the disease and the influence of its course on cognitive performance; the most used tests and batteries for neuropsychological assessment; therapeutic strategies to improve cognitive abilities.

  7. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

    Funder, K S; Steinmetz, J; Rasmussen, L S

    2009-01-01

    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol......This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive...... neuropsychological test battery must be used to detect POCD and a well-matched control group is very useful for the analysis and interpretation of the test RESULTS: Cardiovascular surgery is associated with a high incidence of POCD. Cardiopulmonary bypass was thought to explain this difference, but randomized...

  8. Cognitive Dysfunctions in Epileptic Syndromes

    Directory of Open Access Journals (Sweden)

    Semih Ayta

    2014-05-01

    Full Text Available Some children with epilepsy display a low level of intelligence, learning disabilities, attention deficit hyperactivity disorder, mood disorders and anxiety. Besides specific learning disabilities like reading, writing, arithmetics, learning problems may involve other major areas of intellectual functions such as speech and language, attention, memory, fine motor coordination. Even in the presence of common pathology that leads to epilepsy and mental dysfunctions, seizures cause additional cognitive problems. Age at seizure onset, type of seizures and epileptic syndromes are some variables that determine the effect of epilepsy on cognition. As recurrent seizures may have some negative impact on the developing brain, the use of antiepileptic drugs should be considered not only to aim reducing seizures but also to prevent possible seizure-induced cortical dysfunctions. Epilepsy is a disorder requiring a complicated psychological adjustment for the patients and indeed is a disease that affects the whole family. Thus, the management of epilepsy must include educational, psychotherapeutic and behavioral interventions as well as drug treatment.

  9. COGNITIVE DYSFUNCTIONS IN DIABETIC POLYNEUROPATHY

    Directory of Open Access Journals (Sweden)

    Mirena Valkova

    2011-12-01

    Full Text Available Introduction: The objective of our study was to examine cognitive status, short – term memory, delayed recall and the retention of visual information in diabetics with polyneuropathy and to establish the impacts of some risk factors on cognitive performance.Contingent and methods: We assessed 47 diabetic patients with polyneuropathy, using the Mini Mental State Examination, 10 words test, the Benton visual retention test and the Hamilton scale.Results: Global cognitive dysfunction, decline in verbal memory and visual retention and tendency for depressive mood were observed. We found statistically significant interaction of ageing, sex, severity of pain, duration and late onset of diabetes mellitus (DM on cognitive functioning. Therapy association on cognition was not found.Conclusions: Our study confirms the hypothesis of global cognitive dysfunction, associated with diabetic polyneuropathy. The interactions of sex and pain severity require further study. We arise a hypothesis of asymmetrical brain injury in diabetics.

  10. Psychopathy: cognitive and neural dysfunction.

    Science.gov (United States)

    R Blair, R James

    2013-06-01

    Psychopathy is a developmental disorder marked by emotional deficits and an increased risk for antisocial behavior. It is not equivalent to the diagnosis Antisocial Personality Disorder, which concentrates only on the increased risk for antisocial behavior and not a specific cause-ie, the reduced empathy and guilt that constitutes the emotional deficit. The current review considers data from adults with psychopathy with respect to the main cognitive accounts of the disorder that stress either a primary attention deficit or a primary emotion deficit. In addition, the current review considers data regarding the neurobiology of this disorder. Dysfunction within the amygdala's role in reinforcement learning and the role of ventromedial frontal cortex in the representation of reinforcement value is stressed. Data is also presented indicating potential difficulties within parts of temporal and posterior cingulate cortex. Suggestions are made with respect to why these deficits lead to the development of the disorder.

  11. Ambulatory anaesthesia and cognitive dysfunction

    DEFF Research Database (Denmark)

    Rasmussen, Lars S; Steinmetz, Jacob

    2015-01-01

    serious adverse outcomes, hence difficult to obtain sound scientific evidence for avoiding complications. RECENT FINDINGS: Few studies have assessed recovery of cognitive function after ambulatory surgery, but it seems that both propofol and modern volatile anaesthetics are rational choices for general...... anaesthesia in the outpatient setting. Cognitive complications such as delirium and postoperative cognitive dysfunction are less frequent in ambulatory surgery than with hospitalization. SUMMARY: The elderly are especially susceptible to adverse effects of the hospital environment such as immobilisation...

  12. Cognitive Dysfunction in Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-03-01

    Full Text Available The primary symptom of fibromyalgia is widespread pain with muscle tenderness to light palpation. Howeover many patients report a wide range of symptoms including pain, dyscognition, sleep disturbances, fatigue and mood disorders (frequently depression. Such symptoms seem to be related to one another. Besides, a decrease in concentration and memory disorder has recognised as an independent symptom yet; added into literature under the terms and lsquo;dyscognition' and and lsquo;fibrofog'. Recently clinicians interested in investigations about dyscognition in fibromyalgia syndrome. Cognitive symptoms may be exacerbated by the presence of depression, anxiety, sleep dysorders, endocrine disregulations and pain; but the relationship is unclear. Additionally some of recent studies suggest that insulin resistance may represent a risk factor for memory impairment in these patients. There is lack of standardized tests, treatment methods and studies for understanding pathophysiologic pathways of cognitive problems (memory, concentration in fibromyalgia.

  13. Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment

    OpenAIRE

    Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

    2014-01-01

    Background Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impair...

  14. Psychopathy: cognitive and neural dysfunction

    Science.gov (United States)

    R. Blair, R. James

    2013-01-01

    Psychopathy is a developmental disorder marked by emotional deficits and an increased risk for antisocial behavior. It is not equivalent to the diagnosis Antisocial Personality Disorder, which concentrates only on the increased risk for antisocial behavior and not a specific cause—ie, the reduced empathy and guilt that constitutes the emotional deficit. The current review considers data from adults with psychopathy with respect to the main cognitive accounts of the disorder that stress either a primary attention deficit or a primary emotion deficit. In addition, the current review considers data regarding the neurobiology of this disorder. Dysfunction within the amygdala's role in reinforcement learning and the role of ventromedial frontal cortex in the representation of reinforcement value is stressed. Data is also presented indicating potential difficulties within parts of temporal and posterior cingulate cortex. Suggestions are made with respect to why these deficits lead to the development of the disorder. PMID:24174892

  15. Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

    Science.gov (United States)

    Zhang, Hui; Ma, Li; Yin, Yan-Ling; Dong, Lian-Qiang; Cheng, Gang-Ge; Ma, Ya-Qun; Li, Yun-Feng; Xu, Bai-Nan

    2016-09-01

    The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

    Science.gov (United States)

    Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

    2014-06-30

    Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe

  17. Screening for cognitive dysfunction in unipolar depression

    DEFF Research Database (Denmark)

    Ott, Caroline Vintergaard; Bjertrup, Anne Juul; Jensen, Johan Høy

    2016-01-01

    BACKGROUND: Persistent cognitive dysfunction in unipolar depression (UD) contributes to socio-occupational impairment, but there are no feasible methods to screen for and monitor cognitive dysfunction in this patient group. The present study investigated the validity of two new instruments...... to screen for cognitive dysfunction in UD, and their associations with socio-occupational capacity. METHOD: Participants (n=53) with UD in partial or full remission and healthy control persons (n=103) were assessed with two new screening instruments, the Danish translations of the Screen for Cognitive...... Impairment in Psychiatry (SCIP-D) and Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and with established neuropsychological and self-assessment measures. Depression symptoms and socio-occupational function were rated with the Hamilton Depression Rating Scale and Functional Assessment...

  18. Bipolar Disorder and Cognitive Dysfunction: A Complex Link.

    Science.gov (United States)

    Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Cammisuli, Davide Maria; Di Fiorino, Mario

    2017-10-01

    The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included "bipolar disorder," "cognitive dysfunction," and "dementia." At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.

  19. Methodological issues of postoperative cognitive dysfunction research

    DEFF Research Database (Denmark)

    Funder, Kamilia S; Steinmetz, Jacob; Rasmussen, Lars S

    2010-01-01

    Postoperative cognitive dysfunction (POCD) is a subtle impairment of memory, concentration, and speed of information processing. It is a frequent complication following surgery and can have a debilitating effect on patients' recovery and future prognosis. Neuropsychological testing is needed...... to reveal postoperative cognitive decline, and questionnaires are not useful for this purpose. There is a profound lack of consensus regarding the research methodology for detection of cognitive deterioration, especially the diagnostic criteria. Issues, such as baseline performance, learning effects...

  20. Topiramate Therapy and Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-04-01

    Full Text Available The effects of topiramate (TPA adjunctive therapy on cognition in 22 consecutive patients with intractable epilepsy were studied at the Montreal Neurological Hospital, Quebec, Canada.

  1. Hippocampal insulin resistance and cognitive dysfunction

    NARCIS (Netherlands)

    Biessels, Geert Jan; Reagan, Lawrence P.

    2015-01-01

    Clinical studies suggest a link between type 2 diabetes mellitus (T2DM) and insulin resistance (IR) and cognitive dysfunction, but there are significant gaps in our knowledge of the mechanisms underlying this relationship. Animal models of IR help to bridge these gaps and point to hippocampal IR as

  2. Characterizing postoperative cognitive dysfunction in the elderly

    NARCIS (Netherlands)

    Hovens, Iris Bertha

    2015-01-01

    In the Netherlands, yearly more than 400.000 elderly patients undergo surgery. An estimated ten percent of these patients develops long-lasting postoperative cognitive dysfunction (POCD), associated with a reduced quality of life, increased dependency and worse prognosis. Currently, there is no

  3. Delirium is associated with early postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Rudolph, J.L.; Marcantonio, E.R.; Culley, D.J.

    2008-01-01

    The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects...

  4. Recent developments in Canine Cognitive Dysfunction Syndrome

    Directory of Open Access Journals (Sweden)

    Alejandro Seisdedos Benzal

    2016-04-01

    Full Text Available Canine Cognitive Dysfunction Syndrome (CCD is a neurodegenerative disease affecting aging dogs. CCD is an underdiagnosed disease that involves at least 14% of geriatric dogs, but apparently less than 2% of diseased dogs are diagnosed. There are several physiopathological similarities between Alzheimer disease (AD and CCD, developing amyloid-β deposits in brain parenchyma and blood vessels, brain atrophy and neuronal loss. The clinical signs lead to behavioural changes. They are unspecific and could appear as soon as seven years of age, but are more relevant in senior dogs. The abnormal behaviour could be classified following the acronym DISHA: Disorientation in the immediate environment; altered Interactions with humans and other animals; Sleep-wake cycle disturbances; House-soiling; and changes in Activity levels. There is no specific diagnostic test or biomarker to demonstrate the presence of CCD; therefore, it is often assessed by ruling out other diseases that may cause similar behavioural changes. Veterinarians have to be able to make an accurate account of veterinary history asking for abnormal behaviour that could be misreported by the owners. CCD is a neurodegenerative disorder that cannot be cured. It is possible to delay the progression of the clinical signs and improve the quality of life of patients, but like in AD, the progression of the illness will depend on the individual. There are three treatment pathways, which could be used in combination: drug therapy to improve cognition and reduce anxiety, antioxidant diet and nutraceutical supplements to reduce the progression of the illness, and finally, environmental enrichment to maintain brain activity. The aim of this review article is to contribute to the knowledge of the illness, presenting recent advances in the pathophysiology, diagnosis and treatment of the disease

  5. Cognitive dysfunction in pediatric multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Suppiej A

    2014-07-01

    Full Text Available Agnese Suppiej,1 Elisa Cainelli1,2 1Child Neurology and Clinical Neurophysiology, Pediatric University Hospital, Padua, Italy; 2Lifespan Cognitive Neuroscience Laboratory (LCNL, Department of General Psychology, University of Padua, Italy Abstract: Cognitive and neuropsychological impairments are well documented in adult ­multiple sclerosis (MS. Research has only recently focused on cognitive disabilities in pediatric cases, highlighting some differences between pediatric and adult cases. Impairments in several functions have been reported in children, particularly in relation to attention, processing speed, visual–motor skills, and language. Language seems to be particularly vulnerable in pediatric MS, unlike in adults in whom it is usually preserved. Deficits in executive functions, which are considered MS-specific in adults, have been inconsistently reported in children. In children, as compared to adults, the relationship between cognitive dysfunctions and the two other main symptoms of MS, fatigue and psychiatric disorders, was poorly explored. Furthermore, data on the correlations of cognitive impairments with clinical and neuroimaging features are scarce in children, and the results are often incongruent; interestingly, involvement of corpus callosum and reduced thalamic volume differentiated patients identified as having a cognitive impairment from those without a cognitive impairment. Further studies about pediatric MS are needed in order to better understand the impact of the disease on brain development and the resulting effect on cognitive functions, particularly with respect to different therapeutic strategies. Keywords: central nervous system, child, deficit, IQ, inflammatory demyelination, neuropsychological

  6. Acute cognitive dysfunction after hip fracture

    DEFF Research Database (Denmark)

    Bitsch, M S; Foss, N B; Kristensen, B B

    2006-01-01

    hip fracture surgery in an optimized, multimodal, peri-operative rehabilitation regimen. METHODS: One hundred unselected hip fracture patients treated in a well-defined, optimized, multimodal, peri-operative rehabilitation regimen were included. Patients were tested upon admission and on the second......BACKGROUND: Patients undergoing hip fracture surgery often experience acute post-operative cognitive dysfunction (APOCD). The pathogenesis of APOCD is probably multifactorial, and no single intervention has been successful in its prevention. No studies have investigated the incidence of APOCD after......, fourth and seventh post-operative days with the Mini Mental State Examination (MMSE) score. RESULTS: Thirty-two per cent of patients developed a significant post-operative cognitive decline, which was associated with several pre-fracture patient characteristics, including age and cognitive function...

  7. Biomarkers of postoperative delirium and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Ganna eAndrosova

    2015-06-01

    Full Text Available Elderly surgical patients frequently experience postoperative delirium (POD and the subsequent development of postoperative cognitive dysfunction (POCD. Clinical features include deterioration in cognition, disturbance in attention and reduced awareness of the environment and result in higher morbidity, mortality and greater utilization of social financial assistance. The aging Western societies can expect an increase in the incidence of POD and POCD. The underlying pathophysiological mechanisms have been studied on the molecular level albeit with unsatisfying small research efforts given their societal burden. Here, we review the known physiological and immunological changes and genetic risk factors, identify candidates for further studies and integrate the information into a draft network for exploration on a systems level. The pathogenesis of these postoperative cognitive impairments is multifactorial; application of integrated systems biology has the potential to reconstruct the underlying network of molecular mechanisms and help in the identification of prognostic and diagnostic biomarkers.

  8. Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

    Science.gov (United States)

    Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

    2009-01-01

    Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

  9. Dysfunctional health service conflict: causes and accelerants.

    Science.gov (United States)

    Nelson, H Wayne

    2012-01-01

    This article examines the causes and accelerants of dysfunctional health service conflict and how it emerges from the health system's core hierarchical structures, specialized roles, participant psychodynamics, culture, and values. This article sets out to answer whether health care conflict is more widespread and intense than in other settings and if it is, why? To this end, health care power, gender, and educational status gaps are examined with an eye to how they undermine open communication, teamwork, and collaborative forms of conflict and spark a range of dysfunctions, including a pervasive culture of fear; the deny-and-defend lawsuit response; widespread patterns of hierarchical, generational, and lateral bullying; overly avoidant conflict styles among non-elite groups; and a range of other behaviors that lead to numerous human resource problems, including burnout, higher staff turnover, increased errors, poor employee citizenship behavior, patient dissatisfaction, increased patient complaints, and lawsuits. Bad patient outcomes include decreased compliance and increased morbidity and mortality. Health care managers must understand the root causes of these problems to treat them at the source and implement solutions that avoid negative conflict spirals that undermine organizational morale and efficiency.

  10. Iatrogenic causes of salivary gland dysfunction

    International Nuclear Information System (INIS)

    Schubert, M.M.; Izutsu, K.T.

    1987-01-01

    Saliva is important for maintaining oral health and function. There are instances when medical therapy is intended to decrease salivary flow, such as during general anesthesia, but most instances of iatrogenic salivary gland dysfunction represent untoward or unavoidable side-effects. The clinical expression of the salivary dysfunction can range from very minor transient alteration in saliva flow to a total loss of salivary function. The most common forms of therapy that interfere with salivation are drug therapies, cancer therapies (radiation or chemotherapy), and surgical therapy. These therapies can affect salivation by a number of different mechanisms that include: disruption of autonomic nerve function related to salivation, interference with acinar or ductal cell functions related to salivation, cytotoxicity, indirect effects (vasoconstriction/dilation, fluid and electrolyte balance, etc.), and physical trauma to salivary glands and nerves. A wide variety of drugs is capable of increasing or decreasing salivary flow by mimicking autonomic nervous system actions or by directly acting on cellular processes necessary for salivation: drugs can also indirectly affect salivation by altering fluid and electrolyte balance or by affecting blood flow to the glands. Ionizing radiation can cause permanent damage to salivary glands, damage that is manifest as acinar cell destruction with subsequent atrophy and fibrosis of the glands. Cancer chemotherapy can cause changes in salivation, but the changes are usually much less severe and only transient. Finally, surgical and traumatic injuries interfere with salivation because of either disruption of gland innervation or gross physical damage (or removal) of glandular tissue (including ducts)

  11. Cognitive-Behavioral Erectile Dysfunction Treatment for Gay Men

    Science.gov (United States)

    Hart, Trevor A.; Schwartz, Danielle R.

    2010-01-01

    The purpose of the present paper is to assist cognitive-behavioral therapists who are treating erectile dysfunction among gay men. Little information is available to cognitive-behavioral therapists about the psychological and social effects of erectile dysfunction in this population, or how to incorporate the concerns of gay men with erectile…

  12. Cognitive dysfunction after minor surgery in the elderly

    NARCIS (Netherlands)

    Canet, J.; Raeder, J.; Rasmussen, L.S.; Enlund, M.; Kuipers, H.M.; Hanning, C.D.; Jolles, J.; Korttila, K.; Siersma, V.D.; Dodds, C.; Abildstrom, H.; Sneyd, J.R.; Vila, P.; Johnson, T.; Muñoz Corsini, L.; Silverstein, J.H.; Nielsen, I.K.; Moller, J.T.

    2003-01-01

    Keywords:General anesthesia;minor surgery;out-patient surgery;cognitive dysfunction Background: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study

  13. Cognitive dysfunction in depression - pathophysiology and novel targets.

    Science.gov (United States)

    Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

    2014-01-01

    Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

  14. Cosmic radiation exposure and persistent cognitive dysfunction

    Science.gov (United States)

    Parihar, Vipan K.; Allen, Barrett D.; Caressi, Chongshan; Kwok, Stephanie; Chu, Esther; Tran, Katherine K.; Chmielewski, Nicole N.; Giedzinski, Erich; Acharya, Munjal M.; Britten, Richard A.; Baulch, Janet E.; Limoli, Charles L.

    2016-01-01

    The Mars mission will result in an inevitable exposure to cosmic radiation that has been shown to cause cognitive impairments in rodent models, and possibly in astronauts engaged in deep space travel. Of particular concern is the potential for cosmic radiation exposure to compromise critical decision making during normal operations or under emergency conditions in deep space. Rodents exposed to cosmic radiation exhibit persistent hippocampal and cortical based performance decrements using six independent behavioral tasks administered between separate cohorts 12 and 24 weeks after irradiation. Radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in executive function and reduced rates of fear extinction and elevated anxiety. Irradiation caused significant reductions in dendritic complexity, spine density and altered spine morphology along medial prefrontal cortical neurons known to mediate neurotransmission interrogated by our behavioral tasks. Cosmic radiation also disrupted synaptic integrity and increased neuroinflammation that persisted more than 6 months after exposure. Behavioral deficits for individual animals correlated significantly with reduced spine density and increased synaptic puncta, providing quantitative measures of risk for developing cognitive impairment. Our data provide additional evidence that deep space travel poses a real and unique threat to the integrity of neural circuits in the brain. PMID:27721383

  15. Postoperative cognitive dysfunction : Involvement of neuroinflammation and neuronal functioning

    NARCIS (Netherlands)

    Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Absalom, Anthony R.; Heineman, Erik; van Leeuwen, Barbara L.

    Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.

  16. [Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

    Science.gov (United States)

    Sachs, G; Katschnig, H

    2001-03-01

    Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

  17. Multiple organ dysfunction caused by parathyroid adenoma‑induced ...

    African Journals Online (AJOL)

    We present a 27‑year‑old male with multiple organ dysfunction caused by parathyroid adenoma‑induced primary hyperparathyroidism (PHPT). Initially, the patient experienced a sudden onset of gastrointestinal symptoms, polyuria, polydipsia, bone pain, renal dysfunction, nephrolithiasis, and acute pancreatitis, symptoms ...

  18. Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

    Science.gov (United States)

    Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

    2017-06-01

    Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

  19. Cognitive Developmental Therapy: Aiding Adult Children of Dysfunctional Families.

    Science.gov (United States)

    Towers, David A.

    The works of Kegan and Guidano have presented cognition and emotion as complementary modes of knowing that develop together. Cognition is conceived of as being concerned with the knowledge of reality, and emotions are conceptualized as people's system for knowing of their relationship to that reality. Adult children of dysfunctional families are a…

  20. Depth of anaesthesia and post-operative cognitive dysfunction

    DEFF Research Database (Denmark)

    Steinmetz, J; Funder, K S; Dahl, B T

    2010-01-01

    A deep level of anaesthesia measured by the bispectral index has been found to improve processing speed as one aspect of cognitive function after surgery. The purpose of the present study was to assess the possible effect of the level of anaesthesia on post-operative cognitive dysfunction (POCD) 1...... week after surgery, as assessed by a neuropsychological test battery....

  1. Depth of anaesthesia and post-operative cognitive dysfunction

    DEFF Research Database (Denmark)

    Steinmetz, J; Funder, K S; Dahl, B T

    2010-01-01

    A deep level of anaesthesia measured by the bispectral index has been found to improve processing speed as one aspect of cognitive function after surgery. The purpose of the present study was to assess the possible effect of the level of anaesthesia on post-operative cognitive dysfunction (POCD) 1...

  2. Methodological issues of postoperative cognitive dysfunction research

    DEFF Research Database (Denmark)

    Funder, Kamilia S; Steinmetz, Jacob; Rasmussen, Lars S

    2010-01-01

    to reveal postoperative cognitive decline, and questionnaires are not useful for this purpose. There is a profound lack of consensus regarding the research methodology for detection of cognitive deterioration, especially the diagnostic criteria. Issues, such as baseline performance, learning effects...

  3. Duration of cognitive dysfunction after concussion, and cognitive dysfunction as a risk factor: a population study of young men

    DEFF Research Database (Denmark)

    Teasdale, T W; Engberg, A

    1997-01-01

    : Denmark. SUBJECTS: 1220 young men who had been admitted to hospital for concussion between the ages of 16 and 24 (identified in a national register of admissions) and who had also been cognitively tested by the Danish conscription draft board. MAIN OUTCOME MEASURE: Score on the draft board's cognitive......, the rate of dysfunctional scores was higher (30.4% (158/520)). Apart from suggesting cognitive dysfunction as a risk factor for concussion, this higher proportion seems to relate to the fact that they were typically injured as young adults, whereas those men who were tested after concussion had more often......, more so for young adults than for adolescents....

  4. Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

    Science.gov (United States)

    Martins da Silva, Ana; Cavaco, Sara; Fernandes, Joana; Samões, Raquel; Alves, Cristina; Cardoso, Márcio; Kelly, Jeffery W; Monteiro, Cecília; Coelho, Teresa

    2018-02-01

    Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

  5. Electromagnetic radiation-2450 MHz exposure causes cognition ...

    Indian Academy of Sciences (India)

    83

    Electromagnetic radiation-2450 MHz exposure causes cognition deficit with mitochondrial. 1 ... decrease in levels of acetylcholine, and increase in activity of acetyl ...... neuronal apoptosis and cognitive disturbances in sevoflurane or propofol ...

  6. Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

    Science.gov (United States)

    Barraclough, M; Elliott, R; McKie, S; Parker, B; Bruce, I N

    2015-10-01

    Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE. © The Author(s) 2015.

  7. Cognitive dysfunction in bipolar disorder and schizophrenia

    DEFF Research Database (Denmark)

    Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A

    2015-01-01

    deterioration in either SZ or BD, some findings point to more severe cognitive deficits in patients with early illness onset across both disorders. A compromised pattern of cognitive functioning in individuals at familiar and/or clinical risk to psychosis as well as in first-degree relatives of BD patients...... suggests that early neurodevelopmental factors may play a role in the emergence of cognitive deficits in both disorders. Premorbid intellectual impairment in SZ and at least in a subgroup of patients with BD may be related to a shared genetically determined influence on neurodevelopment....

  8. Electromagnetic radiation 2450 MHz exposure causes cognition ...

    Indian Academy of Sciences (India)

    Sukesh Kumar Gupta

    2018-03-24

    Mar 24, 2018 ... Earlier studies have reported that long term low fre- quency of EMR ... 2.45 GHz at low intensity (50–230HZ) for short time period (15–120 min daily ... lead to cognitive disorders or memory dysfunction in rats. (Lai et al. 1987 ...

  9. Effects of cognitive remediation on cognitive dysfunction in partially or fully remitted patients with bipolar disorder

    DEFF Research Database (Denmark)

    Demant, Kirsa M; Almer, Glennie Marie; Vinberg, Maj

    2013-01-01

    A large proportion of patients with bipolar disorder experience persistent cognitive dysfunction, such as memory, attention and planning difficulties, even during periods of full remission. The aim of this trial is to investigate whether cognitive remediation, a new psychological treatment......, improves cognitive function and, in turn, psychosocial function in patients with bipolar disorder in partial or full remission....

  10. Pathogenesis of irradiation-induced cognitive dysfunction

    International Nuclear Information System (INIS)

    Abayomi, O.K.

    1996-01-01

    Neurocognitive dysfunction is a common sequela of cranial irradiation that is especially severe in young children. The underlying mechanisms of this disorder have not been described. The present review describes the role of the hippocampus and the anatomically related cortex in memory function and its marked susceptibility to ischemic and hypoxic injury. Based on studies of animal models of human amnesia and histopathological findings in the irradiated brain, the neurocognitive sequela of cranial irradiation can be seen to be mediated through vascular injury, resulting in ischemia and hypoxia in the hippocampal region. Recognition of the site and mechanisms of this injury may lead to the development of techniques to minimize the risks. (orig.)

  11. Pathogenesis of irradiation-induced cognitive dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Abayomi, O.K. [Howard Univ. Hospital, Washington, DC (United States). Dept. of Radiation Oncology

    1996-12-31

    Neurocognitive dysfunction is a common sequela of cranial irradiation that is especially severe in young children. The underlying mechanisms of this disorder have not been described. The present review describes the role of the hippocampus and the anatomically related cortex in memory function and its marked susceptibility to ischemic and hypoxic injury. Based on studies of animal models of human amnesia and histopathological findings in the irradiated brain, the neurocognitive sequela of cranial irradiation can be seen to be mediated through vascular injury, resulting in ischemia and hypoxia in the hippocampal region. Recognition of the site and mechanisms of this injury may lead to the development of techniques to minimize the risks. (orig.).

  12. Cognitive dysfunction, MRI findings and manganese levels in alcoholics

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Tsutomu; Nakane, Yoshibumi [Nagasaki Univ. (Japan). School of Medicine; Takahashi, Katsurou; Shimanaga, Masaki [National Nagasaki Medical Center, Omura (Japan)

    2002-12-01

    Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging (MRI) in liver failure, findings that are typically associated with manganese intoxication. The present study compared brain atrophy on T1-weighted MRI, signal intensity ratios of the globus pallidus on T1-weighted MRI, whole blood manganese levels, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ parameters between alcoholics with and without liver cirrhosis, to investigate cognitive dysfunction, MRI findings and manganese levels in alcoholics. Pallidal hyperintensity was visually identified in 80% of alcoholic patients with liver cirrhosis. In addition, a significant correlation was seen between pallidal signal intensity (P.S.I.) ratio and blood manganese level. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis. We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. (author)

  13. Cognitive dysfunction, MRI findings and manganese levels in alcoholics

    International Nuclear Information System (INIS)

    Itoh, Tsutomu; Nakane, Yoshibumi

    2002-01-01

    Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging (MRI) in liver failure, findings that are typically associated with manganese intoxication. The present study compared brain atrophy on T1-weighted MRI, signal intensity ratios of the globus pallidus on T1-weighted MRI, whole blood manganese levels, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ parameters between alcoholics with and without liver cirrhosis, to investigate cognitive dysfunction, MRI findings and manganese levels in alcoholics. Pallidal hyperintensity was visually identified in 80% of alcoholic patients with liver cirrhosis. In addition, a significant correlation was seen between pallidal signal intensity (P.S.I.) ratio and blood manganese level. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis. We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. (author)

  14. New insights into the pathophysiology of postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Krenk, Lene; Rasmussen, Lars Simon; Kehlet, H

    2010-01-01

    There is evidence that postoperative cognitive dysfunction (POCD) is a significant problem after major surgery, but the pathophysiology has not been fully elucidated. The interpretation of available studies is difficult due to differences in neuropsychological test batteries as well as the lack...

  15. Postoperative cognitive dysfunction in middle-aged patients

    NARCIS (Netherlands)

    Johnson, T.; Monk, T.; Rasmussen, L.S.; Abildstrom, H.; Houx, P.J.; Korttila, K.; Kuipers, H.M.; Hanning, C.D.; Siersma, V.D.; Kristensen, D.; Canet, J.; Ibanaz, M.T.; Moller, J.T.

    2002-01-01

    Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent. Methods: The authors compared

  16. Subjective cognitive dysfunction in rehabilitation outpatients with musculoskeletal disorders or chronic pain

    NARCIS (Netherlands)

    Schrier, Ernst; Geertzen, Jan H.; Dijkstra, Pieter U.

    BACKGROUND: Rehabilitation patients, without brain damage, sometimes complain about poor concentration and problems with their memory. The magnitude and associations, of this cognitive dysfunction, with different factors is unclear. AIM: To determine the magnitude of cognitive dysfunction in

  17. Post Operative Cognitive Dysfunction (POCD in Geriatric Population

    Directory of Open Access Journals (Sweden)

    Rajesh MC

    2015-10-01

    Full Text Available Post-operative mental dysfunction and confusion in aged patients is a well recognized entity. Commonly known as post-operative delirium and cognitive dysfunction (POCD, these are important for any peri-operative physician dealing with geriatric population. The incidence is more in older patients with pre-existing impairment. Impact of POCD is grave. This can result in poor rehabilitation outcome and increased hospital stay. Incidence ranges from 15-50% with ˂5% for cataract surgery and as high as 60% after hip replacement procedures.

  18. Sleep and cognitive dysfunctions. Therapeutic approach

    Directory of Open Access Journals (Sweden)

    M.G. Poluektov

    2014-01-01

    Full Text Available This review focuses on the possible mechanisms of sleep disorders in patients with cognitive impairment (CI of different severity. The interrelation between CI, emotional disorders and insomnia, as well as the dependence of CI severity on the degree of sleep disorders, are discussed. The issues related to treatment of sleep disorders in patients with CI, the advantages and disadvantages of modern somnogenic medications are studied. Recommendations on management of patients with a combination of sleep disorders and CI are provided. Data on the use of Egb 761 to treat CI no dementia and melatonin-based drugs to treat sleep disorders in patients with CI are presented. 

  19. The resting state fMRI study of patients with Parkinson's disease associated with cognitive dysfunction

    International Nuclear Information System (INIS)

    Feng Jieying; Huang Biao

    2013-01-01

    Parkinson's disease (PD) is the most common neurodegenerative cause of Parkinsonism, but the high morbidity of PD accompanied cognitive dysfunction hasn't drawn enough attention by the clinicians. With the rapid development of the resting state functional MRI (fMRI) technique, the cause of PD patients with cognitive dysfunction may be associated with the damage of functional connectivity of the motor networks and the cognitive networks. The relationship between neuropathologic mechanism of PD patients with cognitive dysfunction and impaired cognitive circuits will be disclosed by building the changes of brain topological structure in patients. The resting state fMRI study can provide the rationale for prevention, diagnosis and treatment of PD. (authors)

  20. Postoperative delirium and postoperative cognitive dysfunction in the elderly - what are the differences?

    DEFF Research Database (Denmark)

    Krenk, L; Rasmussen, L S

    2011-01-01

    Postoperative cognitive impairment is an increasingly common problem as more elderly patients undergo major surgery. Cognitive deficits in the postoperative period cause severe problems and are associated with a marked increase in morbidity and mortality. There are two main entities of postoperat......Postoperative cognitive impairment is an increasingly common problem as more elderly patients undergo major surgery. Cognitive deficits in the postoperative period cause severe problems and are associated with a marked increase in morbidity and mortality. There are two main entities...... of postoperative cognitive decline, delirium and postoperative cognitive dysfunction, which are often reported as being part of the same continuum. Although there are similarities in the predisposing factors, it seems unlikely that they share the same pathophysiology. Both have multifactorial pathogenesis...... but differ in numerous other ways, with delirium being well-defined and acute in onset and postoperative cognitive dysfunction (POCD) being subtler and with longer duration. This review aims to provide an overview of the differences in the diagnosis of the two entities and to illustrate the methodological...

  1. Brain imaging and cognitive dysfunctions in Huntington's disease

    Science.gov (United States)

    Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

    2006-01-01

    Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

  2. Cognitive dysfunction in depression - pathophysiology and novel targets

    DEFF Research Database (Denmark)

    Carvalho, Andre F; Miskowiak, Kamilla Woznica; Hyphantis, Thomas N

    2014-01-01

    , inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3...... poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having...

  3. Cognitive Impairment in Chronic Alcoholics: Some Cause for Optimism.

    Science.gov (United States)

    Goldman, Mark S.

    1983-01-01

    It appears that, although the cognitive functioning of many alcoholics remains impaired even after drinking has stopped, considerable recovery can occur. New findings now suggest the possibility of reducing cognitive dysfunction and enhancing alcoholism treatment outcomes. (CMG)

  4. Dysfunction of vocal chords as cause of dyspnoea and sibilance

    International Nuclear Information System (INIS)

    Sanabria Rodriguez, Oscar; Bermudez Gomez, Mary; Lobelo, Rafael; Londono Trujillo, Dario; Solarte Rodriguez, Ivan

    2001-01-01

    From the years 80 have been identified the dysfunction and the paralysis of vocal chords (DPVC), like cause of dyspnoea, sibilance and in many occasions truly critical clinical squares that simulate asthmatic crisis. Patients' reports that have required orotracheal intubations and stay in intensive care, when this illness is presented; they improve in a remarkable way when the correct diagnosis of DPVC settles down. The paper include the presentation of the case and discussion

  5. The NCAN gene: schizophrenia susceptibility and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Wang P

    2016-11-01

    Full Text Available Peirong Wang,1 Jun Cai,2 Jianliang Ni,1 Jiangtao Zhang,1 Wei Tang,3 Chen Zhang2 1Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 2Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Wenzhou Kangning Hospital, Wenzhou, Zhejiang, People’s Republic of China Background: Cognitive dysfunction has been recognized as a cardinal feature of schizophrenia. Elucidating the neurobiological substrates of cognitive dysfunction in schizophrenia would help identify the underlying mechanism of this disorder. The rs1064395 single nucleotide polymorphism, within the gene encoding neurocan (NCAN, is reported to be associated with schizophrenia in European populations and may influence brain structure in patients with schizophrenia.Methods: In this study, we aimed to explore whether NCAN rs1064395 confers some risk for schizophrenia and cognitive dysfunction in Han Chinese. We recruited 681 patients with schizophrenia and 699 healthy subjects. Two hundred and fifty-four patients were evaluated according to Repeatable Battery for the Assessment of Neuropsychological Status (RBANS.Results: There were no significant differences in genotype or allele distributions of the rs1064395 polymorphism between the schizophrenia and control groups. Patients showed significantly poorer performance than controls on immediate memory, visuospatial skill, language, attention, delayed memory, and total RBANS score. Patients with the A/A or A/G genotype of rs1064395 had lower scores of immediate memory, visuospatial skill, attention, and total RBANS score than those with the G/G genotype. We performed an expression quantitative trait loci analysis and observed a significant association between rs1064395 and NCAN expression in the frontal (P=0.0022, P=0.022 after Bonferroni correction and cerebellar cortex (P=0.0032, P=0.032 after Bonferroni correction.Conclusion: Our findings indicate

  6. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis

    DEFF Research Database (Denmark)

    Rocca, Maria A; Amato, Maria P; De Stefano, Nicola

    2015-01-01

    In patients with multiple sclerosis (MS), grey matter damage is widespread and might underlie many of the clinical symptoms, especially cognitive impairment. This relation between grey matter damage and cognitive impairment has been lent support by findings from clinical and MRI studies. However...... that causes clinical symptoms to trigger. Findings on cortical reorganisation support the contribution of brain plasticity and cognitive reserve in limiting cognitive deficits. The development of clinical and imaging biomarkers that can monitor disease development and treatment response is crucial to allow...

  7. Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

    Science.gov (United States)

    Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

    2017-10-01

    We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

  8. Cognitive dysfunction among newly diagnosed older patients with hematological malignancy: frequency, clinical indicators and predictors.

    Science.gov (United States)

    Aiki, Sayo; Okuyama, Toru; Sugano, Koji; Kubota, Yosuke; Imai, Fuminobu; Nishioka, Masahiro; Ito, Yoshinori; Iida, Shinsuke; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Akechi, Tatsuo

    2018-01-01

    Medical staff often overlook or underestimate the presence or severity of cognitive dysfunction. The purpose of this study was to clarify the frequency, clinical indicators and predictors of cognitive dysfunction among newly diagnosed older patients with hematologic malignancy receiving first-line chemotherapy. Patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were consecutively recruited. Cognitive dysfunction was evaluated using the Mini-Mental State Examination (MMSE) twice: before starting chemotherapy (T1) and 1 month later (T2). Participants also underwent a comprehensive geriatric assessment at T1. Potential clinical indicators that were associated with cognitive dysfunction were explored via cross-sectional analysis at T1. Predictors of cognitive dysfunction at T2 were also investigated among patients without cognitive dysfunction at T1. A total of 145 participants participated in the study; cognitive dysfunction at T1 was present in 20%. Multivariate analysis demonstrated that lower educational attainment and poorer instrumental activities of daily living were significant clinical indicators of cognitive dysfunction. Among 99 patients who did not have cognitive dysfunction at T1 and underwent cognitive assessment at T2, 7% developed dysfunction. Subjective perception of difficulty remembering at T1 was the only factor which significantly predicted new-onset cognitive dysfunction at T2. The prevalence rate of cognitive dysfunction was non-negligible among older patients with hematologic malignancy before and immediately after initial chemotherapy. Attention to the clinical indicators and predictors found in this study may provide facilitate the identification of cognitive dysfunction in patients with cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Frederic Blanc

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain and VBM for focal brain volume (GM and WM, NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54% had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in

  10. Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

    Science.gov (United States)

    Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

    2017-09-01

    Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

  11. Pelvic floor spasm as a cause of voiding dysfunction.

    Science.gov (United States)

    Kuo, Tricia L C; Ng, L G; Chapple, Christopher R

    2015-07-01

    Pelvic floor disorders can present with lower urinary tract symptoms, bowel, sexual dysfunction, and/or pain. Symptoms of pelvic muscle spasm (nonrelaxing pelvic floor or hypertonicity) vary and can be difficult to recognize. This makes diagnosis and management of these disorders challenging. In this article, we review the current evidence on pelvic floor spasm and its association with voiding dysfunction. To distinguish between the different causes of voiding dysfunction, a video urodynamics study and/or electromyography is often required. Conservative measures include patient education, behavioral modifications, lifestyle changes, and pelvic floor rehabilitation/physical therapy. Disease-specific pelvic pain and pain from pelvic floor spasm needs to be differentiated and treated specifically. Trigger point massage and injections relieves pain in some patients. Botulinum toxin A, sacral neuromodulation, and acupuncture has been reported in the management of patients with refractory symptoms. Pelvic floor spasm and associated voiding problems are heterogeneous in their pathogenesis and are therefore often underrecognized and undertreated; it is therefore essential that a therapeutic strategy needs to be personalized to the individual patient's requirements. Therefore, careful evaluation and assessment of individuals using a multidisciplinary team approach including a trained physical therapist/nurse clinician is essential in the management of these patients.

  12. Total serum homocysteine levels do not identify cognitive dysfunction in multimorbid elderly patients.

    Science.gov (United States)

    Hengstermann, S; Laemmler, G; Hanemann, A; Schweter, A; Steinhagen-Thiessen, E; Lun, A; Schulz, R-J

    2009-02-01

    Total blood homocysteine (Hcys) and folate levels have been investigated in association with cognitive dysfunction in healthy but not in multimorbid elderly patients. We hypothesized that total serum Hcys is an adequate marker to identify multimorbid elderly patients with cognitive dysfunction assessed by the Short Cognitive Performance Test (SKT) and Mini-Mental State Examination (MMSE). Cross-sectional study. The study center was an acute geriatric hospital. A total of 189 multimorbid elderly patients were recruited. Cognitive dysfunction was determined according to the SKT and MMSE. Biochemical parameters (Hcys, folate, vitamin B12, hemoglobin), nutritional status (BMI, Mini Nutritional Assessment, nutritional intake), and activities of daily living were assessed. According to the SKT, 25.4% of patients showed no cerebral cognitive dysfunction, 21.2% had suspected incipient cognitive dysfunction, 12.7% showed mild cognitive dysfunction, 9.0% had moderate cognitive dysfunction, and 31.7% of patients were demented. The median plasma Hcys value was elevated by approximately 20% in multimorbid elderly patients, independent of cognitive dysfunction. Serum folate and vitamin B12 concentrations were within normal ranges. We did not find significant differences in nutritional status, activities of daily living, numbers of diseases or medications, or selected biochemical parameters between the SKT groups. Elevated serum Hcys levels with normal plasma folate and vitamin B12 concentrations were observed in multimorbid elderly patients. The plasma Hcys level did not appear to be an important biological risk factor for cognitive dysfunction in multimorbid geriatric patients.

  13. Cytochrome P450 polymorphism and postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Steinmetz, J; Jespersgaard, Cathrine; Dalhoff, Kim Peder

    2012-01-01

    neuropsychological testing at one week had POCD, and 24 out of 307 (7.8%) had POCD at three months. None of the examined CYP2C19, 2D6 alleles, or various phenotypes were significantly associated with POCD. CONCLUSION: Polymorphisms in CYP2C19, or 2D6 genes do not seem to be related to the occurrence of cognitive......BACKGROUND:The etiology of postoperative cognitive dysfunction (POCD) remains unclear but toxicity of anesthetic drugs and their metabolites could be important. We aimed to assess the possible association between POCD after propofol anesthesia and various phenotypes owing to polymorphisms...... in cytochrome P450 encoding genes. METHODS:We included patients who underwent non-cardiac surgery under total intravenous anesthesia with propofol. POCD was identified using a neuropsychological test-battery administered preoperatively, one week, and three months after surgery. Genotyping of CYP2C19*2, *3, CYP2...

  14. Postoperative cognitive dysfunction and its relationship to cognitive reserve in elderly total joint replacement patients.

    Science.gov (United States)

    Scott, J E; Mathias, J L; Kneebone, A C; Krishnan, J

    2017-06-01

    Whether total joint replacement (TJR) patients are susceptible to postoperative cognitive dysfunction (POCD) remains unclear due to inconsistencies in research methodologies. Moreover, cognitive reserve may moderate the development of POCD after TJR, but has not been investigated in this context. The current study investigated POCD after TJR, and its relationship with cognitive reserve, using a more rigorous methodology than has previously been utilized. Fifty-three older adults (aged 50+) scheduled for TJR were assessed pre and post surgery (6 months). Forty-five healthy controls matched for age, gender, and premorbid IQ were re-assessed after an equivalent interval. Cognition, cognitive reserve, and physical and mental health were all measured. Standardized regression-based methods were used to assess cognitive changes, while controlling for the confounding effect of repeated cognitive testing. TJR patients only demonstrated a significant decline in Trail Making Test Part B (TMT B) performance, compared to controls. Cognitive reserve only predicted change in TMT B scores among a subset of TJR patients. Specifically, patients who showed the most improvement pre to post surgery had significantly higher reserve than those who showed the greatest decline. The current study provides limited evidence of POCD after TJR when examined using a rigorous methodology, which controlled for practice effects. Cognitive reserve only predicted performance within a subset of the TJR sample. However, the role of reserve in more cognitively compromised patients remains to be determined.

  15. Minor neurological dysfunction and cognition in 9-year-olds born at term

    NARCIS (Netherlands)

    Kikkert, Hedwig K; de Jong, Corina; Hadders-Algra, Mijna

    BACKGROUND: In children with developmental disorders, motor problems often co-occur with cognitive difficulties. Associations between specific cognitive deficits underlying learning problems and minor neurological dysfunction (MND) are still unknown. AIMS: To assess associations between specific

  16. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  17. TorsinA dysfunction causes persistent neuronal nuclear pore defects.

    Science.gov (United States)

    Pappas, Samuel S; Liang, Chun-Chi; Kim, Sumin; Rivera, CheyAnne O; Dauer, William T

    2018-02-01

    A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons. We find that during postnatal CNS maturation torsinA null neurons develop mislocalized and dysfunctional nuclear pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis. SUN1, a torsinA-related molecule implicated in interphase NPC biogenesis, also exhibits localization abnormalities. Whereas SUN1 and associated nuclear membrane abnormalities resolve in juvenile mice, NPC defects persist into adulthood. These findings support a role for torsinA function in NPC biogenesis during neuronal maturation and implicate altered NPC function in dystonia pathophysiology. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Molecular mechanisms of cognitive dysfunction following traumatic brain injury

    Science.gov (United States)

    Walker, Kendall R.; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533

  19. Molecular mechanisms of cognitive dysfunction following traumatic brain injury.

    Science.gov (United States)

    Walker, Kendall R; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.

  20. How well do the ADAS-cog and its subscales measure cognitive dysfunction in Alzheimer's disease?

    Science.gov (United States)

    Benge, Jared F; Balsis, Steve; Geraci, Lisa; Massman, Paul J; Doody, Rachelle S

    2009-01-01

    The Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) is regularly used to assess cognitive dysfunction in Alzheimer's disease (AD) clinical trials. Yet, little is known about how the instrument and its subscales measure cognition across the spectrum of AD. The current investigation used item response theory (IRT) analyses to assess the measurement properties of the ADAS-cog across the range of cognitive dysfunction in AD. We used IRT-based analyses to establish the relationship between cognitive dysfunction and the probability of obtaining observed scores on each subscale and the test as a whole. Data were obtained from 1,087 patients with AD and amnestic mild cognitive impairment. Results showed that the ADAS-cog and its subscales provide maximum information at moderate levels of cognitive dysfunction. Raw score differences toward the lower and higher ends of the scale corresponded to large differences in cognitive dysfunction, whereas raw score differences toward the middle of the scale corresponded to smaller differences. The utility of the ADAS-cog and its subscales is optimal in the moderate range of cognitive dysfunction, but raw score differences in that region correspond to relatively small differences in cognitive dysfunction. Implications for tracking and staging dementia and for clinical trials are discussed. Copyright 2009 S. Karger AG, Basel.

  1. Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

    Science.gov (United States)

    Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

    2014-12-01

    To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  2. Neuropsychiatric disorders and cognitive dysfunction in patients with Cushing's disease.

    Science.gov (United States)

    Chen, Yu-fan; Li, Yun-feng; Chen, Xiao; Sun, Qing-fang

    2013-08-01

    To review the main neuropsychiatric disorders and cognitive deficits in patients with Cushing's disease (CD) and the associated pathophysiological mechanisms underlying CD. These mechanistic details may provide recommendations for preventing or treating the cognitive impairments and mood disorders in patients with CD. Data were obtained from papers on psychiatric and cognitive complications in CD published in English within the last 20 years. To perform the PubMed literature search, the following keywords were input: cushing's disease, cognitive, hippocampal, or glucocorticoids. Studies were selected if they contained data relevant to the topic addressed in the particular section. Because of the limited length of this article, we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers. Patients with active CD not only suffer from many characteristic clinical features, but also show some neuropsychiatric disorders and cognitive impairments. Among the psychiatric manifestations, the common ones are emotional instability, depressive disorder, anxious symptoms, impulsivity, and cognitive impairment. Irreversible effects of previous glucocorticoid (GC) excess on the central nervous system, such as hippocampal and the basal ganglia, is the most reasonable reason. Excess secretion of cortisol brings much structural and functional changes in hippocampal, such as changes in neurogenesis and morphology, signaling pathway, gene expression, and glutamate accumulation. Hippocampal volume loss can be found in most patients with CD, and decreased glucose utilization caused by GCs may lead to brain atrophy, neurogenesis impairment, inhibition of long-term potentiation, and decreased neurotrophic factors; these may also explain the mechanisms of GC-induced brain atrophy and hippocampal changes. Brain atrophy and hippocampal changes caused by excess secretion of cortisol are thought to play a significant

  3. Is postoperative cognitive dysfunction a risk factor for dementia?

    DEFF Research Database (Denmark)

    Steinmetz, J; Siersma, Volkert Dirk; Kessing, L V

    2013-01-01

    BACKGROUND: /st>Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after major surgery. An association between POCD and the development of dementia has been suspected. In this study, we assessed if POCD was a risk factor for the occurrence of dementia. METHODS...... surgery, using a neuropsychological test battery. The time of (first) occurrence of dementia after surgery was assessed using the National Patient Register and the Psychiatric Central Research Register. Recorded dementia diagnoses (ICD-8 and ICD-10) were: Alzheimer's disease, vascular dementia......, frontotemporal dementia, or dementia without specification. The risk of dementia according to POCD was assessed in the Cox regression models. RESULTS: /st>A total of 686 patients with a median age of 67 [inter-quartile range (IQR) 61-74] yr were followed for a median of 11.1 (IQR 5.2-12.6) yr. Only 32 patients...

  4. Long-term consequences of postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Steinmetz, Jacob; Christensen, Karl Bang; Lund, Thomas

    2009-01-01

    BACKGROUND: Postoperative cognitive dysfunction (POCD) is common in elderly patients after noncardiac surgery, but the consequences are unknown. The authors' aim was to determine the effects of POCD on long-term prognosis. METHODS: This was an observational study of Danish patients enrolled in two...... on survival, labor market attachment, and social transfer payments were obtained from administrative databases. The Cox proportional hazards regression model was used to compute relative risk estimates for mortality and disability, and the relative prevalence of time on social transfer payments was assessed......, and cancer). The risk of leaving the labor market prematurely because of disability or voluntary early retirement was higher among patients with 1-week POCD (hazard ratio, 2.26 [1.24-4.12]; P = 0.01). Patients with POCD at 1 week received social transfer payments for a longer proportion of observation time...

  5. Metabolic Syndrome, Insulin Resistance and Cognitive Dysfunction: Does your metabolic profile affect your brain?

    DEFF Research Database (Denmark)

    Neergaard, Jesper S; Møller, Katrine Dragsbæk; Christiansen, Claus

    2017-01-01

    with 44% (9%-91%) larger probability of developing cognitive dysfunction. In addition subjects above the HOMA-IR threshold (HOMA-IR > 2.6) had 47% (9%-99%) larger odds of cognitive dysfunction. The associations could indicate that a significant proportion of dementia cases in women is likely...

  6. Maternal Depressive Symptoms, Dysfunctional Cognitions, and Infant Night Waking: The Role of Maternal Nighttime Behavior

    Science.gov (United States)

    Teti, Douglas M.; Crosby, Brian

    2012-01-01

    Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via…

  7. Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

    Science.gov (United States)

    Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

    2016-09-01

    Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

  8. Danger in the Air: Air Pollution and Cognitive Dysfunction.

    Science.gov (United States)

    Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Borin, Gemma

    2018-01-01

    Clean air is considered to be a basic requirement for human health and well-being. To examine the relationship between cognitive performance and ambient pollution exposure. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Air pollution is a multifaceted toxic chemical mixture capable of assaulting the central nervous system. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on cognitive function in both adults and children. Consistent evidence showed that exposure to air pollution, specifically exposure to particulate matter, caused poor age-related cognitive performance. Living in areas with high levels of air pollution has been linked to markers of neuroinflammation and neuropathology that are associated with neurodegenerative conditions such as Alzheimer's disease-like brain pathologies.

  9. Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Helen P McWilliams-Koeppen

    Full Text Available Light chain (AL amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(PH-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.

  10. PET Scans Obtained for Evaluation of Cognitive Dysfunction

    Science.gov (United States)

    Silverman, Daniel H. S.; Mosconi, Lisa; Ercoli, Linda; Chen, W; Small, Gary W.

    2015-01-01

    The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism with devastating neuropathologic, economic, social and clinical consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are carried out with [18F]fluorodeoxyglucose (FDG) as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment, and in distinguishing among primary neurodegenerative disorders and other etiologies for cognitive decline. In addition to focusing upon the effects on cerebral metabolism examined with FDG PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact upon the enormous human toll exacted by these diseases. PMID:18514081

  11. A Clinical Research Study of Cognitive Dysfunction and Affective Impairment after Isolated Brainstem Stroke

    Directory of Open Access Journals (Sweden)

    Xiujuan Fu

    2017-12-01

    Full Text Available Although the function of the cerebellum in neurocognition has been well-documented, the similar role of the brainstem has yet to be fully elucidated. This clinical research study aimed to combine data relating to neuropsychological assessments and P300 to explore cognitive dysfunction and affective impairment following brainstem stroke. Thirty-four patients with isolated brainstem stroke and twenty-six healthy controls were recruited; for each patient, we collated data pertaining to the P300, Addenbrooke's Cognitive Examination III (ACE-III, Montreal Cognitive Assessment Chinese version (MoCA, trail-making test (TMT, Symbol Digit Modalities Test (SDMT, Wechsler Adult Intelligence Scale-Digit Spans (DS, Stroop test, Self Rating Depression Scale (SDS, and Self Rating Anxiety Scale (SAS. Significance was analyzed using an independent T-test or the Mann-Whitney U-test. Correlation was analyzed using Pearson's correlation analysis or Spearman's correlation analysis. Collectively, data revealed that brainstem stroke caused mild cognitive impairment (MCI, and that visuospatial, attention, linguistic, and emotional disturbances may occur after isolated brainstem stroke. Cognitive decline was linked to P300 latency, ACE-III, and MoCA; P300 latency was correlated with ACE-III. Patients with right brainstem lesions were more likely to suffer memory decline. The present study provides initial data relating to the role of the brainstem in neurocognition, and will be useful for further understanding of vascular cognitive and affective impairment.

  12. A Clinical Research Study of Cognitive Dysfunction and Affective Impairment after Isolated Brainstem Stroke

    Science.gov (United States)

    Fu, Xiujuan; Lu, Zuneng; Wang, Yan; Huang, Lifang; Wang, Xi; Zhang, Hong; Xiao, Zheman

    2017-01-01

    Although the function of the cerebellum in neurocognition has been well-documented, the similar role of the brainstem has yet to be fully elucidated. This clinical research study aimed to combine data relating to neuropsychological assessments and P300 to explore cognitive dysfunction and affective impairment following brainstem stroke. Thirty-four patients with isolated brainstem stroke and twenty-six healthy controls were recruited; for each patient, we collated data pertaining to the P300, Addenbrooke's Cognitive Examination III (ACE-III), Montreal Cognitive Assessment Chinese version (MoCA), trail-making test (TMT), Symbol Digit Modalities Test (SDMT), Wechsler Adult Intelligence Scale-Digit Spans (DS), Stroop test, Self Rating Depression Scale (SDS), and Self Rating Anxiety Scale (SAS). Significance was analyzed using an independent T-test or the Mann-Whitney U-test. Correlation was analyzed using Pearson's correlation analysis or Spearman's correlation analysis. Collectively, data revealed that brainstem stroke caused mild cognitive impairment (MCI), and that visuospatial, attention, linguistic, and emotional disturbances may occur after isolated brainstem stroke. Cognitive decline was linked to P300 latency, ACE-III, and MoCA; P300 latency was correlated with ACE-III. Patients with right brainstem lesions were more likely to suffer memory decline. The present study provides initial data relating to the role of the brainstem in neurocognition, and will be useful for further understanding of vascular cognitive and affective impairment. PMID:29311895

  13. Evidence of cognitive dysfunction after soccer playing with ball heading using a novel tablet-based approach.

    Directory of Open Access Journals (Sweden)

    Marsha R Zhang

    Full Text Available Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point as well as indirect, goal-driven, or voluntary point responses (Anti-Point, thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction.

  14. Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach

    Science.gov (United States)

    Lin, Angela H.; Patel, Saumil S.; Sereno, Anne B.

    2013-01-01

    Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction. PMID:23460843

  15. Analysis of the Role of Neurospecific Proteins in the Diagnosis of Cognitive Dysfunction in Patients with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Yulia Gennad'evna Samoylova

    2014-04-01

    Full Text Available Background. Impairment of the central nervous system manifested as cognitive dysfunction caused by metabolic or structural changes is a severe progressive vascular complication of type 1 diabetes mellitus (T1DM. Significant difficulties in the diagnosis of cognitive dysfunction are associated with subjective diagnostic techniques. Objective. To identify the role of neurospecific markers in the diagnosis of cognitive dysfunction in patients with T1DM. Materials and Methods. A total of 58 patients with T1DM aged 16?30 years were included in this study. The control group included 29 healthy young adults matched by gender and age. The survey included clinical and laboratory examinations, psychological testing and magnetic resonance imaging (MRI of the brain. The Montreal Cognitive Assessment (MoCA was used to screen for cognitive impairment. The levels of neurospecific proteins (S100, glial fibrillary acidic protein and myelin basic protein were determined to identify early markers of cognitive impairment. MRI of the brain was performed using a Siemens Magnetom 1.0 T system to assess structural changes in the central nervous system. Results. The study revealed increased levels of all neurospecific proteins, which correlated with parameters of hyperglycaemia and cognitive deficit (MoCA scores of

  16. A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis.

    Science.gov (United States)

    Rabinowitz, Amanda R; Arnett, Peter A

    2009-09-01

    Using a longitudinal design, the authors examined coping and cognitive functioning in the development of depression in individuals with multiple sclerosis (MS). Coping style was evaluated in 2 conceptually distinct roles: as moderator and mediator of the impact of cognitive dysfunction on depression. Using indices derived from the COPE (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989), the authors operationalized coping in 3 ways-as active, avoidant, and an index accounting for relative levels of both. Coping both moderated and partially mediated the relationship between cognitive dysfunction and depression. Moderation results suggest that the relationship between cognitive dysfunction and depression is dependent on coping style-adaptive coping protects individuals from experiencing depression related to their cognitive deficits; however, when individuals use maladaptive coping, cognitive dysfunction puts them at risk for depression. Mediational results suggest that cognitive dysfunction leads to depression partially due to cognitive dysfunction's effects on coping. That is, cognitive deficits may impair individuals' ability to use adaptive coping strategies, leaving them more likely to use maladaptive strategies. Clinical and theoretical implications of these findings are discussed.

  17. Foodborne cereulide causes beta-cell dysfunction and apoptosis.

    Directory of Open Access Journals (Sweden)

    Roman Vangoitsenhoven

    Full Text Available To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function.Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6 and rat (INS-1E beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1. Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS. Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests.24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05. Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05 and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein. Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05 and reactive oxygen species increased by more than twofold (P<0.05 following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively.Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.

  18. Green Tea Consumption Affects Cognitive Dysfunction in the Elderly: A Pilot Study

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    Kazuki Ide

    2014-09-01

    Full Text Available Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J score: <28 participated in the study (2 men, 10 women; mean age, 88 years. The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants’ MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03. This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.

  19. Prevalence and predictors of cognitive dysfunction in opioid-treated patients with cancer: a multinational study

    DEFF Research Database (Denmark)

    Kurita, Geana P; Sjøgren, Per; Ekholm, Ola

    2011-01-01

    with opioids for moderate or severe pain for at least 3 days were included. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). MMSE scores were categorized into definite cognitive dysfunction (scores ... (scores > 26). Factors potentially associated with cognitive dysfunction were assessed. Associations between MMSE and explanatory variables were analyzed by ordinal logistic regression models. Results We included 1,915 patients with cancer from 17 centers. MMSE scores less than 27 were observed in 32......-treated patients with cancer had possible or definite cognitive dysfunction. Lung cancer, daily opioid doses of 400 mg or more (oral morphine equivalents), older age, low KPS, shorter time since cancer diagnosis, and absence of BTP were predictors for cognitive dysfunction....

  20. Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Rebecca M Shansky

    2013-04-01

    Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

  1. Cognitive Rehabilitation for Executive Dysfunction in Parkinson's Disease: Application and Current Directions

    Directory of Open Access Journals (Sweden)

    Jessica Calleo

    2012-01-01

    Full Text Available Cognitive dysfunction in Parkinson's disease contributes to disability, caregiver strain, and diminished quality of life. Cognitive rehabilitation, a behavioral approach to improve cognitive skills, has potential as a treatment option to improve and maintain cognitive skills and increase quality of life for those with Parkinson's disease-related cognitive dysfunction. Four cognitive rehabilitation programs in individuals with PD are identified from the literature. Characteristics of the programs and outcomes are reviewed and critiqued. Current studies on cognitive rehabilitation in PD demonstrate feasibility and acceptability of a cognitive rehabilitation program for patients with PD, but are limited by their small sample size and data regarding generalization of effects over the long term. Because PD involves progressive heterogeneous physical, neurological, and affective difficulties, future cognitive rehabilitation programs should aim for flexibility and individualization, according to each patient's strengths and deficits.

  2. Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly.

    Science.gov (United States)

    Hogan, Kirk J; Bratzke, Lisa C; Hogan, Kendra L

    2018-02-01

    Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%-15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.

  3. Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood?

    Directory of Open Access Journals (Sweden)

    Namitha Nair

    2018-01-01

    Full Text Available Background: Children with seizure disorder are often treated with sodium valproate (SV on long-term basis. SV acts mainly through gamma amino butyric acid pathways, reducing the excitatory neurotransmission and modifying the monoamine concentration. Altered monoamine concentration by SV is expected to cause movement disorder and cognitive dysfunction, considered reversible after the withdrawal of treatment, but some claim it to be irreversible. It is not clear whether such adverse effects continue during adulthood. The aim of this study was to investigate whether chronic administration of SV in juvenile rats causes movement disorder and cognitive dysfunction during their early adulthood. Methods: Sixteen-day-old male Wistar rats from the central animal house, KMC, Mangalore, India in 2015, received either 200 or 400 mg/kg dose of SV for 45 consecutive days and another group served as control. Thirty days after discontinuation of the drug, at postnatal day 90, the rats were tested for movement disorder and cognitive function. Results: Chronic SV treatment in juvenile rats resulted in slow movement, tremors during adulthood but did not affect muscle tone, locomotor and exploratory activities. It also caused cognitive dysfunction in adult rats. Conclusion: Despite the reported safety of chronic SV therapy, its adverse effects such as Parkinsonism symptoms or cognitive dysfunctions should be of concern in all young patients treated with SV for many years. Persistence of cognitive impairment, tremors and generalized slow movement during adulthood after cessation of treatment that was observed in this study, warrants a close monitoring system in children who receive long-term sodium valproate.

  4. Intermittent pacemaker dysfunction caused by digital mobile telephones.

    Science.gov (United States)

    Naegeli, B; Osswald, S; Deola, M; Burkart, F

    1996-05-01

    This study was designed to evaluate possible interactions between digital mobile telephones and implanted pacemakers. Electromagnetic fields may interfere with normal pacemaker function. Development of bipolar sensing leads and modern noise filtering techniques have lessened this problem. However, it remains unclear whether these features also protect from high frequency noise arising from digital cellular phones. In 39 patients with an implanted pacemaker (14 dual-chamber [DDD], 8 atrial-synchronized ventricular-inhibited [VDD(R)] and 17 ventricular-inhibited [VVI(R)] pacemakers), four mobile phones with different levels of power output (2 and 8 W) were tested in the standby, dialing and operating mode. During continuous electrocardiographic monitoring, 672 tests were performed in each mode with the phones positioned over the pulse generator, the atrial and the ventricular electrode tip. The tests were carried out at different sensitivity settings and, where possible, in the unipolar and bipolar pacing modes as well. In 7 (18%) of 39 patients, a reproducible interference was induced during 26 (3.9%) of 672 tests with the operating phones in close proximity (phone and at maximal sensitivity of the pacemakers (maximal vs. nominal sensitivity, 6% vs. 1.8% positive test results, p = 0.009). When the bipolar and unipolar pacing modes were compared in the same patients, ventricular inhibition was induced only in the unipolar mode (12.5% positive test results, p = 0.0003). Digital mobile phones in close proximity to implanted pacemakers may cause intermittent pacemaker dysfunction with inappropriate ventricular tracking and potentially dangerous pacemaker inhibition.

  5. Reducing dysfunctional beliefs about sleep does not significantly improve insomnia in cognitive behavioral therapy.

    Science.gov (United States)

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the baseline and at the end of treatment. The results showed that although cognitive behavioral therapy for insomnia greatly reduced individuals' scores on both scales, the decrease in dysfunctional beliefs and attitudes about sleep with treatment did not seem to mediate improvement in insomnia. The findings suggest that sleep-related dysfunctional beliefs endorsed by patients with chronic insomnia may be attenuated by cognitive behavioral therapy for insomnia, but changes in such beliefs are not likely to play a crucial role in reducing the severity of insomnia.

  6. Postoperative cognitive dysfunction and neuroinflammation; Cardiac surgery and abdominal surgery are not the same

    NARCIS (Netherlands)

    Hovens, Iris B.; van Leeuwen, Barbara L.; Mariani, Massimo A.; Kraneveld, Aletta D.; Schoemaker, Regien G.

    Postoperative cognitive dysfunction (POCD) is a debilitating surgical complication, with cardiac surgery patients at particular risk. To gain insight in the mechanisms underlying the higher incidence of POCD after cardiac versus non-cardiac surgery, systemic and central inflammatory changes,

  7. COGNOS : Care for People With Cognitive Dysfunction A National Observational Study

    NARCIS (Netherlands)

    Mets, Tony; De Deyn, Peter P.; Pals, Philippe; De Lepeleire, Jan; Vandewoude, Maurits; Ventura, Manfredi; Ivanoiu, Adrian; Albert, Adelin; Seghers, An-Katrien

    2013-01-01

    Care plans are intended to improve the independence and functioning of patients with cognitive dysfunction and support the caregivers involved. They are an integral part of the Belgian reimbursement procedure for cholinesterase inhibitors. This nationwide, multicenter, observational study examined

  8. Duration of Thyroid Dysfunction Correlates with All-Cause Mortality

    DEFF Research Database (Denmark)

    Laulund, Anne Sofie; Nybo, Mads; Brix, Thomas Heiberg

    2014-01-01

    INTRODUCTION AND AIM: The association between thyroid dysfunction and mortality is controversial. Moreover, the impact of duration of thyroid dysfunction is unclarified. Our aim was to investigate the correlation between biochemically assessed thyroid function as well as dysfunction duration...... and Charlson Comorbidity Index (CCI) was used as comorbidity score. RESULTS: Hazard ratios (HR) with 95% confidence intervals (CI) for mortality with decreased (elevated (>4.0 mIU/L) levels of TSH were 2.22; 2.14-2.30; P..., gender, CCI and diagnostic setting attenuated the risk estimates (HR 1.23; 95% CI: 1.19-1.28; Pelevated values of TSH, respectively. Mortality risk increased by a factor 1...

  9. Prevalence of diastolic dysfunction as a possible cause of dyspnea in the elderly

    DEFF Research Database (Denmark)

    Pedersen, Frants; Raymond, Ilan; Mehlsen, Jesper

    2005-01-01

    Symptoms in patients with heart failure and preserved left ventricular ejection fraction may be caused by isolated diastolic dysfunction. The purpose of this study was to assess the prevalence of diastolic dysfunction as a potential cause of dyspnea in a sample of elderly subjects, as well as of ...

  10. Reducing Dysfunctional Beliefs about Sleep Does Not Significantly Improve Insomnia in Cognitive Behavioral Therapy

    OpenAIRE

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the...

  11. Cognitive dysfunction after fast-track hip and knee replacement.

    Science.gov (United States)

    Krenk, Lene; Kehlet, Henrik; Bæk Hansen, Torben; Solgaard, Søren; Soballe, Kjeld; Rasmussen, Lars Simon

    2014-05-01

    Postoperative cognitive dysfunction (POCD) is reported to occur after major surgery in as many as 20% of patients, elderly patients may especially experience problems in the weeks and months after surgery. Recent studies vary greatly in methods of evaluation and diagnosis of POCD, and the pathogenic mechanisms are still unclear. We evaluated a large uniform cohort of elderly patients in a standardized approach, after major joint replacement surgery (total hip and knee replacement). Patients were in an optimized perioperative approach (fast track) with multimodal opioid-sparing analgesia, early mobilization, and short length of stay (LOS ≤3 days) and discharged to home. In a prospective multicenter study, we included 225 patients aged ≥60 years undergoing well-defined fast-track total hip or total knee replacement. Patients had neuropsychological testing preoperatively and 1 to 2 weeks and 3 months postoperatively. LOS, pain, opioid use, inflammatory response, and sleep quality were recorded. The practice effect of repeated cognitive testing was gauged using data from a healthy community-dwelling control group (n = 161). Median LOS was 2 days (interquartile range 2-3). The incidence of POCD at 1 to 2 weeks was 9.1% (95% confidence interval [CI], 5.4%-13.1%) and 8.0% (95% CI, 4.5%-12.0%) at 3 months. There was no statistically significant difference between patients with and without early POCD, regarding pain, opioid use, sleep quality, or C-reactive protein response, although the CIs were wide. Patients with early POCD had a higher Mini Mental State Examination score preoperatively (difference in medians 0.5 [95% CI, -1.0% to 0.0%]; P = 0.034). If there was an association between early POCD and late POCD, the sample size was unfortunately too small to verify this (23.6% of patients with early POCD had late onset vs 6.7% in non-POCD group; risk difference 16.9 (95% CI, -2.1% to 41.1%; P = 0.089). The incidence of POCD early after total hip and knee replacement

  12. Thyroid function, Alzheimer's disease and postoperative cognitive dysfunction: a tale of dangerous liaisons?

    Science.gov (United States)

    Mafrica, Federica; Fodale, Vincenzo

    2008-05-01

    Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. Moreover, thyroid hormones negatively regulate expression of the amyloid-beta protein precursor (AbetaPP), which plays a key role in the development of AD. A condition, the so called euthyroid sick syndrome (ESS), characterized by reduced serum T_{3} and T_{4} concentrations without increased serum thyroid stimulation hormone secretion, occurs within hours after major surgery. After surgery, elderly patients often exhibit a transient, reversible state of cognitive alterations. Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.

  13. Megalourethra as a rare cause for erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Robert Pallas, MD, Bch

    2015-01-01

    Full Text Available MRI findings of megalourethra have not previously been reported. We present a case of an adult presenting with lifelong erectile dysfunction secondary to poor development of the corpus spongiosum and corpora cavernosa. The pathogenesis, typical presentation, and treatment of megalourethra, as well as the use of modern imaging techniques to aid in the diagnosis and treatment of this disease are discussed.

  14. Change in Dysfunctional Beliefs About Sleep in Behavior Therapy, Cognitive Therapy, and Cognitive-Behavioral Therapy for Insomnia.

    Science.gov (United States)

    Eidelman, Polina; Talbot, Lisa; Ivers, Hans; Bélanger, Lynda; Morin, Charles M; Harvey, Allison G

    2016-01-01

    As part of a larger randomized controlled trial, 188 participants were randomized to behavior therapy (BT), cognitive therapy (CT), or cognitive-behavioral therapy (CBT) for insomnia. The aims of this study were threefold: (a) to determine whether change in dysfunctional beliefs about sleep was related to change in sleep, insomnia symptoms, and impairment following treatment; (b) to determine whether BT, CT, and CBT differ in their effects on dysfunctional beliefs; and (c) to determine whether the treatments differ in their effects on particular kinds of dysfunctional beliefs. Beliefs, sleep, insomnia symptoms, and sleep-related psychosocial impairment were assessed at pretreatment, posttreatment, and 6- and 12-month follow-up. Greater change in dysfunctional beliefs occurring over the course of BT, CT, or CBT was associated with greater improvement in insomnia symptoms and impairment at posttreatment and both follow-ups. All groups experienced a significant decrease in dysfunctional beliefs during treatment, which were sustained through 6- and 12-month follow-up. Compared with the BT group, a greater proportion of participants in the CT and/or CBT groups endorsed dysfunctional beliefs below a level considered clinically significant at posttreatment and 12-month follow-up. The results demonstrate the importance of targeting dysfunctional beliefs in insomnia treatment, suggest that beliefs may be significantly modified with BT alone, and indicate that cognitive interventions may be particularly powerful in enhancing belief change. Copyright © 2016. Published by Elsevier Ltd.

  15. Costovertebral joint dysfunction: another misdiagnosed cause of atypical chest pain.

    Science.gov (United States)

    Arroyo, J. F.; Jolliet, P.; Junod, A. F.

    1992-01-01

    The diagnostic work-up of atypical chest pain frequently leads to invasive procedures. However, this painful symptomatology can sometimes be of benign origin and respond to simple therapeutic manoeuvres. A number of musculoskeletal conditions such as costovertebral joint dysfunctions should be carefully considered. We report five cases in which patient discomfort and high costs could have been avoided if awareness of these conditions had led to a correct diagnosis upon initial physical examination. PMID:1448407

  16. Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

    Science.gov (United States)

    Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

    2018-05-02

    We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.

    Science.gov (United States)

    Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun

    2013-05-01

    This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

  18. Tirapazamine causes vascular dysfunction in HCT-116 tumour xenografts

    International Nuclear Information System (INIS)

    Huxham, Lynsey A.; Kyle, Alastair H.; Baker, Jennifer H.E.; McNicol, Krista L.; Minchinton, Andrew I.

    2006-01-01

    Background and purpose: Tirapazamine is a hypoxic cytotoxin currently undergoing Phase II/III clinical evaluation in combination with radiation and chemotherapeutics for the treatment of non-hematological cancers. Tissue penetration studies using multicellular models have suggested that tirapazamine exposure may be limited to cells close to blood vessels. However, animal studies show tirapazamine enhances the anti-tumour activity of radiation and chemotherapy and clinical studies with tirapazamine, so far, are promising. To investigate this apparent paradox we examined the microregional effects of tirapazamine in vivo by mapping drug effects with respect to the position of blood vessels in tumour cryosections. Patients and methods: Tirapazamine was administered i.p. to mice bearing HCT-116 tumours, which were excised at various times after treatment. Images of multiple-stained cryosections were overlaid to provide microregional information on the relative position of proliferating cells, hypoxia, perfusion and vasculature. Results: We observed extensive and permanent vascular dysfunction in a large proportion of tumours from mice treated with tirapazamine. In the affected tumours, blood flow ceased in the centrally located tumour vessels, leaving a rim of functional vessels around the periphery of the tumour. This vascular dysfunction commenced within 24 h after tirapazamine administration and the areas affected appeared to be replaced by necrosis over the following 24-48 h. Conclusions: Because the majority of hypoxic cells are located in the center of tumours we propose that the activity of tirapazamine in vivo may be related to its effects on tumour vasculature and that its activity against hypoxic cells located distal to functional blood vessels may not be as important as previously believed

  19. Psychological determinants of erectile dysfunction: testing a cognitive-emotional model.

    Science.gov (United States)

    Nobre, Pedro J

    2010-04-01

    Recent studies have shown the impact of sexual dysfunctional beliefs, negative cognitive schemas, negative automatic thoughts, and depressed affect on male erectile dysfunction. Despite this fact, there are only few conceptual models that try to integrate these findings, and more importantly, there is a lack of studies that test the validity of those conceptual models. The aim of the present article was to test a cognitive-emotional model for erectile dysfunction. Taking previous research findings into account, we developed a cognitive-emotional model for erectile disorder (ED) and used path analysis to test it. A total of 352 men (303 participants from the general population and 49 participants with a DSM-IV diagnosis of sexual dysfunction) answered a set of questionnaires assessing cognitive and emotional variables. Erectile Function measured by the EF subscale of the International Index of Erectile Function, cognitive schemas measured by the Questionnaire of Cognitive Schema Activation in Sexual Context, sexual beliefs measured by the Sexual Dysfunctional Beliefs Questionnaire, thoughts and emotions measured by the Sexual Modes Questionnaire. The effects of the main proposed direct predictors explained 55% of the erectile function variance (R = 0.74). Most remaining direct effects proposed in the model were also statistically significant. The analysis of the absolute residuals showed that most of the implied correlations were close to the observed zero order correlations, indicated the adjustment of the model to the observed data. These findings support the role played by cognitive and emotional factors on the predisposition and maintenance of male erectile dysfunction and suggest important implications for assessment and treatment of ED.

  20. Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Renan Bazuco Frittoli

    2016-06-01

    Full Text Available Abstract Objective To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE. Methods Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC. The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p < 0.05 was adopted. Results 41 patients with a mean age of 14.5 ± 2.84 years were included. Cognitive dysfunction was noted in 17 (41.46% patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p = 0.039. Anxiety symptoms were observed in 8 patients (19.51% and were associated with visual perception (p = 0.037 and symptoms of depression were observed in 1 patient (2.43%. Conclusion Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment.

  1. Choice reaction time in patients with post-operative cognitive dysfunction

    DEFF Research Database (Denmark)

    Steinmetz, J.; Rasmussen, L.S.

    2008-01-01

    BACKGROUND: Post-operative cognitive dysfunction (POCD) is detected by administration of a neuropsychological test battery. Reaction time testing is at present not included as a standard test. Choice reaction time (CRT) data from the first International Study of Post-operative Cognitive Dysfunction...... in nine countries. CRT was measured 52 times using the four boxes test. Patients performed the test before surgery (n=1083), at 1 week (n=926) and at 3 months (n=852) post-operatively. CRT for the individual patient was determined as the median time of correct responses. The usefulness of the CRT...... had a significantly longer CRT. ROC curves revealed that a reaction time of 813 ms was the most appropriate cut-off at 1 week and 762 ms at 3 months but the positive predictive value for POCD was low: 34.4% and 14.7%, respectively. CONCLUSIONS: Post-operative cognitive dysfunction is associated...

  2. Is previous hyperthyroidism associated with long-term cognitive dysfunction?

    DEFF Research Database (Denmark)

    Lillevang-Johansen, Mads; Petersen, Inge; Christensen, Kaare

    2014-01-01

    National Patient Registry and 3036 twin pairs from The Danish Twin Registry, who had participated in nationwide surveys on health conditions. MEASUREMENTS: Among other investigations, survey participants had carried out cognitive tests including a Mini-Mental State Exam (MMSE) and six separate cognitive...... tests. Based on five of the tests a composite cognitive score was calculated. RESULTS: 55 out of 3036 twin pairs were discordant for hyperthyroidism. The mean time from diagnosis until survey participation was 7.3 years (range: 0-24.1 years). In both the intra-pair and individual level analyses......, the hyperthyroid twin scored significantly better in the MMSE than did the healthy co-twin (p=0.023 and p=0.038, respectively). The same tendency was found in the other cognitive tests, and after analysing twins diagnosed with hyperthyroidism more than two years before participating, although none were...

  3. Pathogenesis of cognitive dysfunction in phenylketonuria : Review of hypotheses

    NARCIS (Netherlands)

    de Groot, M. J.; Hoeksma, M.; Blau, N.; Reijngoud, D. J.; van Spronsen, F. J.

    2010-01-01

    In untreated phenylketonuria (PKU), deficiency of phenylalanine hydroxylase (PAH) results in elevated blood phenylalanine (Phe) concentrations and severe mental retardation. Current dietary treatment prevents mental retardation, but cognitive outcome remains suboptimal. The mechanisms by which

  4. Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

    Science.gov (United States)

    Das, Devsmita; Phillips, Cristy; Hsieh, Wayne; Sumanth, Krithika; Dang, Van; Salehi, Ahmad

    2014-10-03

    Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration. Published by Elsevier Inc.

  5. Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction.

    Science.gov (United States)

    Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

    2014-01-15

    This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

  6. Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

    Science.gov (United States)

    Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

    2016-01-01

    Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

  7. Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

    Directory of Open Access Journals (Sweden)

    Flavie Darcet

    2016-02-01

    Full Text Available Major Depressive Disorder (MDD is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed.

  8. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    Science.gov (United States)

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

  9. Intravenous Milrinone Infusion Improves Congestive Heart Failure Caused by Diastolic Dysfunction

    Science.gov (United States)

    Albrecht, Carlos A.; Giesler, Gregory M.; Kar, Biswajit; Hariharan, Ramesh; Delgado, Reynolds M.

    2005-01-01

    Although there have been significant advances in the medical treatment of heart failure patients with impaired systolic function, very little is known about the diagnosis and treatment of diastolic dysfunction. We report the cases of 3 patients in New York Heart Association functional class IV who had echocardiographically documented diastolic dysfunction as the main cause of heart failure. All 3 patients received medical therapy with long-term milrinone infusion. PMID:16107121

  10. Cognitive and Emotional Dysfunction after Central Pontine Myelinolysis

    Directory of Open Access Journals (Sweden)

    Tatia M. C. Lee

    2003-01-01

    Full Text Available The case of a 67-year-old right-handed Chinese man with Central Pontine Myelinolysis [CPM] is described to illustrate the resulting cognitive and emotional disturbances. A comparison of the data in this report with that in published studies suggests that ethnicity does not seem to have much effect on the symptoms of CPM. Possible underlying neural-pathological mechanisms are discussed. This case further substantiates the speculation that the brainstem plays a role in higher cognitive processes and emotional regulation.

  11. The emerging role of norepinephrine in cognitive dysfunctions of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Elena eVazey

    2012-07-01

    Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disorder, affecting 1% of the population over age 60. In those patients cognitive dysfunction is a persistent issue that impairs quality of life and productivity. Neuropathological studies demonstrate significant damage in brain regions outside the nigral dopamine (DA system, including early degeneration of locus coeruleus norepinephrine (LC-NE neurons, yet discussion of PD and treatment focus has remained dopaminergic-based. Motor symptoms benefit from DA replacement for many years, but other symptoms including several cognitive deficits continue unabated. Recent interest in non-DA substrates of PD highlights early involvement of LC-NE neurons and provides evidence for a prodromal phase, with cognitive disturbance, even in sporadic PD. We outline insights from basic research in LC-NE function to clinical and pathological evidence highlighting a role for NE in PD cognitive dysfunction. We propose that loss of LC-NE regulation, particularly in higher cortical regions, critically underlies certain cognitive dysfunctions in early PD. As a major unmet need for patients, research and use of NE drugs in PD may provide significant benefits for cognitive processing.

  12. The relationship between cognitive dysfunction and stress sensitivity in schizophrenia

    NARCIS (Netherlands)

    Morrens, M.; Krabbendam, L.; Bak, M.L.F.J.; Delespaul, P.A.E.G.; Mengelers, R.; Sabbe, B.G.C.; Hulstijn, W.; Os, J. van; Myin-Germeys, I.

    2007-01-01

    The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop

  13. Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.

    Science.gov (United States)

    Pascual, María; Baliño, Pablo; Alfonso-Loeches, Silvia; Aragón, Carlos M G; Guerri, Consuelo

    2011-06-01

    Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Predictors of Cognitive Dysfunction among Patients with Moderate to Severe Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Uduak Effiong Williams

    2017-04-01

    Full Text Available Cognitive dysfunction including dementia is a common complication of chronic kidney disease (CKD that has just been recently appreciated. It has negative outcomes in the management of patients with CKD. This study explored the possible biochemical and clinical features of patients with CKD that can predict the occurrence of cognitive impairment in patients with moderate to severe CKD. We evaluate patients with stages 3-5 CKD for the occurrence and predictors of cognitive impairment. Multiple areas of cognitive function were tested in this single-center study using Community Screening Interview for Dementia (CSID and Trial-Making Test A (TMTA/Trial-Making Test B (TMTB. Cognitive impairment was correlated with patients’ routine biochemical, hematological, and selected clinical parameters. We observed a negative correlation between cognitive impairment and patient’s serum calcium (r = 0.240; p = 0.033 and estimated Glomerular filtration rate (eGFR (r = 0.379; p = 0.0006. Therefore, eGFR is an accurate predictor of cognitive dysfunction in patients with moderate to severe CKD. Early evaluation of cognitive function in CKD is indeed advised for optimal outcome in the management of patients with CKD.

  15. Risk Factors for Postoperative Cognitive Dysfunctions in Elderly Patients

    Directory of Open Access Journals (Sweden)

    N. Yu. Ibragimov

    2008-01-01

    Full Text Available Objective: to study the impact of a wide spectrum of factors on the development of postoperative delirium in elderly patients in relation to the changes in their cognitive functions depending on the type of anesthesia and period after surgery. Subjects and methods. The study covered 100 patients aged 65—90 years who had been electively operated on under general, regional, and combined anesthesia. Their cognitive status was elevated before and 1, 4, and 7 days after surgery, by using the Mini-Mental State Examination (MMSE schedule. The diagnosis was postoperatively established on the basis of interviews, by applying the diagnostic criteria of ICD-10 and DSM-IV (American Psychiatric Association, 1994 and verified by a psychiatrist’s consultation. Results. Seventeen patients developed delirium within the first two days following surgery. Elevated plasma sodium (p<0.000001, leukocytosis (p<0.00002, and postoperative analgesia mode (p<0.02 proved to be statistically significant risk factors for delirium. Worse results of MMSE tests at all postoperative stages than those obtained prior to surgery were significant (p<0.05. Comparing the results obtained on days 1, 4, and 7 showed a significant cognitive improvement. Analysis indicated no significant differences in MMSE changes between the groups of general, regional, and combined anesthesia at all study stages. Conclusion. In elderly patients, surgery and anesthesia lead to a considerable deterioration of cognitive functions even if the development of delirium can be avoided. There is a significant correlation of the development of delirium with leukocytosis, hypernatremia, and postoperative analgesia mode. Key words: anesthesia, postoperative delirium, cognitive status, MMSE, elderly age.

  16. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats

    NARCIS (Netherlands)

    Hovens, Iris B.; van Leeuwen, Barbara L.; Nyakas, Csaba; Heineman, Erik; van der Zee, Eddy A.; Schoemaker, Regien G.

    Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We

  17. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study

    NARCIS (Netherlands)

    Moller, J.T.; Cluitmans, P.J.M.; Rasmussen, L.S.; Houx, P.J.; Rasmussen, H.; Canet, J.; Rabbitt, P.; Jolles, J.; Larsen, K.; Hanning, C.D.; Langeron, O.; Johnson, T.; Lauven, P.M.; Kristensen, P.A.; Biedler, A.; Beem, van H.; Fraidakis, O.; Silverstein, J.H.; Beneken, J.E.W.; Gravenstein, J.S.

    1998-01-01

    Summary Background Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. Methods 1218 patients aged at least 60 years

  18. Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

    NARCIS (Netherlands)

    Rasmussen, L.S.; O'Brien, J.T.; Silverstein, J.H.; Johnson, T.; Siersma, V.D.; Canet, J.; Jolles, J.; Hanning, C.D.; Kuipers, H.M.; Abildstrom, H.; Papaioannou, A.; Raeder, J.; Yli-Hankala, A.; Sneyd, J.R.; Munoz, L.; Moller, J.T.

    2005-01-01

    Background: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in

  19. Cognitive Dysfunction, Locus of Control and Treatment Outcome among Chronic Alcoholics.

    Science.gov (United States)

    Abbott, Max W.

    While alcoholism is no longer regarded as a unitary disorder, conventional measures of congition and personality have yet to be shown capable of consistently predicting clinical outcomes. To investigate cognitive dysfunction and locus of control as predictors of post treatment outcome in a large sample of alcoholics, 106 alcoholics (74 men, 32…

  20. Cognitive dysfunction in young men following head injury in childhood and adolescence: a population study

    DEFF Research Database (Denmark)

    Teasdale, T W; Engberg, A W

    2003-01-01

    admissions and the draft board, 3091 young men were identified who had been injured before age 18 and tested at age 18 or shortly thereafter: 970 had suffered a single concussion and were in hospital for one day only; 521 had two concussions at separate times and were in hospital for one day only on each...... Danish men appearing before the draft board had a score classified as dysfunctional). RESULTS: For young men who had suffered a single concussion, cranial fracture, or cerebral lesion before 12 years of age, resulting in less than 12 days of hospital admission (n = 376), rates of cognitive dysfunction.......0, irrespective of age at injury. For cases of two concussions, all odds ratios were > 1.4 but were not significant for all age groupings. CONCLUSIONS: For milder forms of single head injury before age 12 there is no evidence of enduring cognitive dysfunction. The apparent effect at later ages may reflect...

  1. [Nicorandil improves cognitive dysfunction in mice with streptozotocin-induced diabetes].

    Science.gov (United States)

    Yan, Wen-Hui; Zhang, Chun-Xi; Xing, Tong; Gong, Xue; Yang, Yu-Xuan; Li, Yi-Nuo; Liu, Xuan; Ayijiang, Jiamaliding; Yu, Ye; Zhang, Meng; Chen, Li-Na

    2018-04-20

    To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes. C57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined. Compared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue. Nicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by

  2. Development and initial validation of a brief self-report measure of cognitive dysfunction in fibromyalgia.

    Science.gov (United States)

    Kratz, Anna L; Schilling, Stephen G; Goesling, Jenna; Williams, David A

    2015-06-01

    Pain is often the focus of research and clinical care in fibromyalgia (FM); however, cognitive dysfunction is also a common, distressing, and disabling symptom in FM. Current efforts to address this problem are limited by the lack of a comprehensive, valid measure of subjective cognitive dysfunction in FM that is easily interpretable, accessible, and brief. The purpose of this study was to leverage cognitive functioning item banks that were developed as part of the Patient Reported Outcomes Measurement Information System (PROMIS) to devise a 10-item short form measure of cognitive functioning for use in FM. In study 1, a nationwide (U.S.) sample of 1,035 adults with FM (age range = 18-82, 95.2% female) completed 2 cognitive item pools. Factor analyses and item response theory analyses were used to identify dimensionality and optimally performing items. A recommended 10-item measure, called the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI) was created. In study 2, 232 adults with FM completed the MISCI and a legacy measure of cognitive functioning that is used in FM clinical trials, the Multiple Ability Self-Report Questionnaire (MASQ). The MISCI showed excellent internal reliability, low ceiling/floor effects, and good convergent validity with the MASQ (r = -.82). This paper presents the MISCI, a 10-item measure of cognitive dysfunction in FM, developed through classical test theory and item response theory. This brief but comprehensive measure shows evidence of excellent construct validity through large correlations with a lengthy legacy measure of cognitive functioning. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction.

    Science.gov (United States)

    Pleet, Michelle L; Mathiesen, Allison; DeMarino, Catherine; Akpamagbo, Yao A; Barclay, Robert A; Schwab, Angela; Iordanskiy, Sergey; Sampey, Gavin C; Lepene, Benjamin; Nekhai, Sergei; Aman, M J; Kashanchi, Fatah

    2016-01-01

    Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we examined the effect of Ebola structural proteins VP40, GP, NP and VLPs on recipient immune cells, as well as the effect of exosomes containing these proteins on naïve immune cells. We found that VP40-transfected cells packaged VP40 into exosomes, and that these exosomes were capable of inducing apoptosis in recipient immune cells. Additionally, we show that presence of VP40 within parental cells or in exosomes delivered to naïve cells could result in the regulation of RNAi machinery including Dicer, Drosha, and Ago 1, which may play a role in the induction of cell death in recipient immune cells. Exosome biogenesis was regulated by VP40 in transfected cells by increasing levels of ESCRT-II proteins EAP20 and EAP45, and exosomal marker proteins CD63 and Alix. VP40 was phosphorylated by Cdk2/Cyclin complexes at Serine 233 which could be reversed with r-Roscovitine treatment. The level of VP40-containing exosomes could also be regulated by treated cells with FDA-approved Oxytetracycline. Additionally, we utilized novel nanoparticles to safely capture VP40 and other viral proteins from Ebola VLPs spiked into human samples using SDS/reducing agents, thus minimizing the need for BSL-4 conditions for most downstream assays. Collectively, our data indicates that VP40 packaged into exosomes may be responsible for the deregulation

  4. Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Michelle L. Pleet

    2016-11-01

    Full Text Available Ebola virus (EBOV is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80–90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we examined the effect of Ebola structural proteins VP40, GP, NP and VLPs on recipient immune cells, as well as the effect of exosomes containing these proteins on naïve immune cells. We found that VP40-transfected cells packaged VP40 into exosomes, and that these exosomes were capable of inducing apoptosis in recipient immune cells. Additionally, we show that presence of VP40 within parental cells or in exosomes delivered to naïve cells could result in the regulation of RNAi machinery including Dicer, Drosha, and Ago 1, which may play a role in the induction of cell death in recipient immune cells. Exosome biogenesis was regulated by VP40 in transfected cells by increasing levels of ESCRT-II proteins EAP20 and EAP45, and exosomal marker proteins CD63 and Alix. VP40 was phosphorylated by Cdk2/Cyclin complexes at Serine 233 which could be reversed with r-Roscovitine treatment. The level of VP40-containing exosomes could also be regulated by treated cells with FDA-approved Oxytetracycline. Additionally, we utilized novel nanoparticles to safely capture VP40 and other viral proteins from Ebola VLPs spiked into human samples using SDS/reducing agents, thus minimizing the need for BSL-4 conditions for most downstream assays. Collectively, our data indicates that VP40 packaged into exosomes may be responsible

  5. Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

    Science.gov (United States)

    Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

    2008-12-01

    This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

  6. Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury.

    Science.gov (United States)

    Ichkova, Aleksandra; Rodriguez-Grande, Beatriz; Bar, Claire; Villega, Frederic; Konsman, Jan Pieter; Badaut, Jerome

    2017-12-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effects of Short-Term Cognitive Remediation on Cognitive Dysfunction in Partially or Fully Remitted Individuals with Bipolar Disorder

    DEFF Research Database (Denmark)

    Demant, Kirsa M; Vinberg, Maj; Kessing, Lars V

    2015-01-01

    for the primary outcome analysis, calculation of the 95% confidence interval showed that it was highly unlikely that an increase in sample size would have rendered any beneficial effects of CR vs. ST on the verbal memory. CONCLUSIONS: Short-term group-based CR did not seem to improve overall cognitive...... aimed to investigate the effects of CR on persistent cognitive dysfunction in BD. METHOD: Patients with BD in partial remission with cognitive complaints were randomised to 12 weeks group-based CR (n=23) or standard treatment (ST) (n=23). Outcomes were improved verbal memory (primary), sustained...... or psychosocial function in individuals with BD in full or partial remission. The present findings suggest that that longer-term, more intensive and individualised CR may be necessary to improve cognition in BD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01457235....

  8. Recurrent pannus formation causing prosthetic aortic valve dysfunction: Is excision without valve re-replacement applicable?

    OpenAIRE

    Darwazah Ahmad K

    2012-01-01

    Abstract Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function. The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replace...

  9. Cognitive dysfunction after fast-track hip and knee replacement

    DEFF Research Database (Denmark)

    Krenk, Lene; Kehlet, Henrik; Bæk Hansen, Torben

    2014-01-01

    to 2 weeks and 3 months postoperatively. LOS, pain, opioid use, inflammatory response, and sleep quality were recorded. The practice effect of repeated cognitive testing was gauged using data from a healthy community-dwelling control group (n = 161). RESULTS: Median LOS was 2 days (interquartile range...... this (23.6% of patients with early POCD had late onset vs 6.7% in non-POCD group; risk difference 16.9 (95% CI, -2.1% to 41.1%; P = 0.089). CONCLUSIONS: The incidence of POCD early after total hip and knee replacement seems to be lower after a fast-track approach than rates previously reported...

  10. A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

    2010-05-01

    Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

  11. Post-operative cognitive dysfunction in the elderly: A prospective clinical study

    Directory of Open Access Journals (Sweden)

    Nalini Kotekar

    2014-01-01

    Full Text Available Background and Aims: Aging population is a major demographic trend worldwide. Globally, 50% of all the elderly individuals are estimated to undergo atleast one surgical procedure and post-operative cognitive dysfunction (POCD is one of the most common and often poorly understood post-operative complications in this section of the population. This randomised prospective study was conducted to assess the post-operative cognitive status in the elderly undergoing non-cardiac surgery, evaluate the cognitive parameters affected, evaluate the potential risk factors and thereby analyse the potential for implementation of preventive strategies. Methods: This study was conducted on 200 patients aged 60 years or older scheduled for elective non-cardiac surgeries. The baseline cognitive status of the patients was assessed 2 days prior to the date of the surgery. The post-operative cognitive status was assessed on the 3 rd day, 7 th day and after 1 month. Statistical analysis was performed using SAS and SPSS. Results: The incidence of POCD showed a gradual decline from postoperative day 3 to 30. Females were found to be at significant risk in developing POCD. Advancing age and level of education emerged as dominant factors, while type of anaesthesia, duration of surgery, and presence of coexisting comorbidities had no influence on the incidence of cognitive dysfunction. Conclusion: POCD is a definite complication after surgery and anaesthesia in the elderly population. Gender emerged as a significant risk factor with increasing age as a dominating factor contributing to POCD.

  12. Perioperative plasma concentrations of stable nitric oxide products are predictive of cognitive dysfunction after laparoscopic cholecystectomy.

    LENUS (Irish Health Repository)

    Iohom, G

    2012-02-03

    In this study our objectives were to determine the incidence of postoperative cognitive dysfunction (POCD) after laparoscopic cholecystectomy under sevoflurane anesthesia in patients aged >40 and <85 yr and to examine the associations between plasma concentrations of i) S-100beta protein and ii) stable nitric oxide (NO) products and POCD in this clinical setting. Neuropsychological tests were performed on 42 ASA physical status I-II patients the day before, and 4 days and 6 wk after surgery. Patient spouses (n = 13) were studied as controls. Cognitive dysfunction was defined as deficit in one or more cognitive domain(s). Serial measurements of serum concentrations of S-100beta protein and plasma concentrations of stable NO products (nitrate\\/nitrite, NOx) were performed perioperatively. Four days after surgery, new cognitive deficit was present in 16 (40%) patients and in 1 (7%) control subject (P = 0.01). Six weeks postoperatively, new cognitive deficit was present in 21 (53%) patients and 3 (23%) control subjects (P = 0.03). Compared with the "no deficit" group, patients who demonstrated a new cognitive deficit 4 days postoperatively had larger plasma NOx at each perioperative time point (P < 0.05 for each time point). Serum S-100beta protein concentrations were similar in the 2 groups. In conclusion, preoperative (and postoperative) plasma concentrations of stable NO products (but not S-100beta) are associated with early POCD. The former represents a potential biochemical predictor of POCD.

  13. Cognitive structures in women with sexual dysfunction: the role of early maladaptive schemas.

    Science.gov (United States)

    Oliveira, Cátia; Nobre, Pedro J

    2013-07-01

    Cognitive schemas are often related to psychological problems. However, the role of these structures within sexual problems is not yet well established. The aim of this study was to evaluate the presence and importance of early maladaptive schemas on women's sexual functioning and cognitive schemas activated in response to negative sexual events. A total of 228 women participated in the study: a control sample of 167 women without sexual problems, a subclinical sample of 37 women with low sexual functioning, and a clinical sample of 24 women with sexual dysfunction. Participants completed several self-reported measures: the Schema Questionnaire, the Questionnaire of Cognitive Schema Activation in Sexual Context, the Brief Symptom Inventory, the Beck Depression Inventory, and the Female Sexual Function Index. Findings indicated that women with sexual dysfunction presented significantly more early maladaptive schemas from the Impaired Autonomy and Performance domain, particularly failure (P depreciation (P < 0.01, η(2) = 0.05), and difference/loneliness (P < 0.01, η(2) = 0.05) schemas. Results supported differences between women with and without sexual problems regarding cognitive factors. This may have implications for the knowledge, assessment, and treatment of sexual dysfunction in women. © 2012 International Society for Sexual Medicine.

  14. Rational pharmacological approaches for cognitive dysfunction and depression in Parkinson's disease.

    Science.gov (United States)

    Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

    2015-01-01

    Parkinson's disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) "Parkinson disease"; "Delirium," "Dementia," "Amnestic," "Cognitive disorders," and "Parkinson disease"; "depression," "major depressive disorder," "drug therapy." We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs.

  15. Rational Pharmacological Approaches for Cognitive Dysfunction and Depression in Parkinson’s Disease

    Science.gov (United States)

    Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

    2015-01-01

    Parkinson’s disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) “Parkinson disease”; “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders,” and “Parkinson disease”; “depression,” “major depressive disorder,” “drug therapy.” We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs. PMID:25873910

  16. Effect of Area-Level Socioeconomic Deprivation on Risk of Cognitive Dysfunction in Older Adults.

    Science.gov (United States)

    McCann, Adrian; McNulty, Helene; Rigby, Jan; Hughes, Catherine F; Hoey, Leane; Molloy, Anne M; Cunningham, Conal J; Casey, Miriam C; Tracey, Fergal; O'Kane, Maurice J; McCarroll, Kevin; Ward, Mary; Moore, Katie; Strain, J J; Moore, Adrian

    2018-02-12

    To investigate the relationship between area-level deprivation and risk of cognitive dysfunction. Cross-sectional analysis. The Trinity, Ulster, and Department of Agriculture (TUDA) study from 2008 to 2012. Community-dwelling adults aged 74.0 ± 8.3 without dementia (N = 5,186; 67% female). Adopting a cross-jurisdictional approach, geo-referenced address-based information was used to map and link participants to official socioeconomic indicators of deprivation within the United Kingdom and the Republic of Ireland. Participants were assigned an individual deprivation score related to the smallest administrative area in which they lived. These scores were categorized into comparable quintiles, that were then used to integrate the datasets from both countries. Cognitive health was assessed using the Mini-Mental State Examination (MMSE); cognitive dysfunction was defined as a MMSE score of 24 or less. Approximately one-quarter of the cohort resided within the most-deprived districts in both countries. Greater area-level deprivation was associated with significantly lower MMSE scores; fewer years of formal education; greater anxiety, depression, smoking and alcohol use, and obesity; and more adverse outcomes, including higher blood pressure and diabetes risk. After adjustment for relevant covariates, area deprivation was associated with significantly higher risk of cognitive dysfunction (odds ratio =1.40, 95% confidence interval = 1.05-1.87, P = .02, for most vs least deprived). This analysis combining data from two health systems shows that area deprivation is an independent risk factor for cognitive dysfunction in older adults. Adults living in areas of greatest socioeconomic deprivation may benefit from targeted strategies aimed at improving modifiable risk factors for dementia. Further cross-national analysis investigating the impact of area-level deprivation is needed to address socioeconomic disparities and shape future policy to improve health outcomes in older

  17. Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes.

    Science.gov (United States)

    Alvarez, Edgardo O; Beauquis, Juan; Revsin, Yanina; Banzan, Arturo M; Roig, Paulina; De Nicola, Alejandro F; Saravia, Flavia

    2009-03-02

    Type 1 diabetes (T1D) is accompanied by a "diabetic encephalopathy" including hypersensitivity to stress, increased risk of stroke, dementia and cognitive impairment. In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both spontaneous and streptozotocin-induced models of experimental T1D. The aim of this study was to explore in streptozotocin-treated mice and other parameters associated to mild neurodegeneration in the dentate gyrus and the potential correlation with behavioural changes. The neurogenic status, measured by doublecortin (DCX) expression, showed an important decline in the number of positive cells in the subgranular zone (SGZ). However, neuronal migration was not affected. We found a marked enhancement of intracellular lipofuscin deposits, characteristic of increased oxidative stress and aging in both, the hilus and the SGZ and granular cell layer (GCL). Diabetic mice showed a significant impairment in learning and memory tests, exhibiting a higher latency to show an escape response and a poorer learning efficiency of an active avoiding response compared with control mice. Both, exploratory and non-exploratory activities in a conflictive environment in the asymmetric elevated plus maze were not affected by the diabetic condition. In conclusion, experimental diabetes showed clear signs of changes in the dentate gyrus, changes similar to those present in the aging process. Correlatively, these alterations were in line with a reduced performance in learning and memory tests. The mechanism that could potentially link neural and behavioural disturbances is not yet fully comprehended.

  18. Overview of Social Cognitive Dysfunctions in Rare Developmental Syndromes With Psychiatric Phenotype

    Directory of Open Access Journals (Sweden)

    Aurore Morel

    2018-05-01

    Full Text Available Rare neurodevelopmental syndromes often present social cognitive deficits that may underlie difficulties in social interactions and increase the risk of psychosis or autism spectrum disorders. However, little is known regarding the specificities of social cognitive impairment across syndromes while it remains a major challenge for the care. Our review provides an overview of social cognitive dysfunctions in rare diseases associated with psychiatric symptoms (with a prevalence estimated between 1 in 1,200 and 1 in 25,000 live births: 22q11.2 deletion syndrome, Angelman syndrome, Fragile X syndrome, Klinefelter syndrome, Prader–Willi syndrome, Rett syndrome, Smith–Magenis syndrome, Turner syndrome, and Williams syndrome and shed some light on the specific mechanisms that may underlie these skills in each clinical presentation. We first detail the different processes included in the generic expression “social cognition” before summarizing the genotype, psychiatric phenotype, and non-social cognitive profile in each syndrome. Then, we offer a systematic review of the social cognitive abilities and the disturbed mechanisms they are likely associated with. We followed the PRISMA process, including the definition of the relevant search terms, the selection of studies based on clear inclusion, and exclusion criteria and the quality appraisal of papers. We finally provide insights that may have considerable influence on the development of adapted therapeutic interventions such as social cognitive training (SCT therapies specifically designed to target the psychiatric phenotype. The results of this review suggest that social cognition impairments share some similarities across syndromes. We propose that social cognitive impairments are strongly involved in behavioral symptoms regardless of the overall cognitive level measured by intelligence quotient. Better understanding the mechanisms underlying impaired social cognition may lead to adapt

  19. Cognitive dysfunction in patients with chronic obstructive pulmonary disease - A systematic review

    DEFF Research Database (Denmark)

    Schou, Lone; Østergaard, Birte; Rasmussen, Lars S

    2012-01-01

    BACKGROUND: Substantial healthcare resources are spent on chronic obstructive pulmonary disease (COPD). In addition, the involvement of patients in monitoring and treatment of their condition has been suggested. However, it is important to maintain a view of self-care that takes differences...... in cognitive ability into account. The aim of this study was to determine the occurrence and severity of cognitive dysfunction in COPD patients, and to assess the association between severity of COPD and the level of cognitive function. METHODS: We conducted a systematic review, and a search in the following...... databases: Medline, PsychINFO, Cochrane Library, EMBASE, CINAHL, and SweMed up to July 2010. The articles were included if(1) participants were patients with COPD,(2) relevant outcome was cognitive function investigated by a neuropsychological test battery, and(3) the severity of COPD had been assessed...

  20. GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Guillermo Gonzalez-Burgos

    2011-01-01

    Full Text Available Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

  1. GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

    Science.gov (United States)

    Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

    2011-01-01

    Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

  2. Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer's Disease

    DEFF Research Database (Denmark)

    Schütt, Trine; Helboe, Lone; Pedersen, Lars Østergaard

    2016-01-01

    Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study...... was to characterize certain aspects of neuropathology and inflammatory markers related to aging and CCD in dogs in comparison with human AD. Fifteen brains from aged dogs with normal cognitive function, mild cognitive impairment, or CCD were investigated and compared with two control brains from young dogs and brain...... sections from human AD subjects. The neuropathological investigations included evaluation of amyloid-β (Aβ) plaque deposition (N-terminally truncated and pyroglutamyl-modified Aβ included), tau pathology, and inflammatory markers in prefrontal cortex. Cortical Aβ deposition was found to be only...

  3. Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

    DEFF Research Database (Denmark)

    Blinkenberg, Morten; Mathiesen, Henrik K; Tscherning, Thomas

    2012-01-01

    and neurological disability. METHODS: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically......OBJECTIVES: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal...... deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction...

  4. Cognitive dysfunction in hereditary spastic paraplegias and other motor neuron disorders

    Directory of Open Access Journals (Sweden)

    Ingrid Faber

    Full Text Available ABSTRACT Hereditary spastic paraplegia (HSP is a diverse group of single-gene disorders that share the predominant clinical feature of progressive lower limb spasticity and weakness. More than 70 different genetic subtypes have been described and all modes of inheritance are possible. Intellectual dysfunction in HSP is frequent in recessive forms but rare in dominant families. It may manifest by either mental retardation and/or cognitive decline. The latter may be subtle, restricted to executive dysfunction or may evolve to severe dementia. The cognitive profile is thought to depend largely on the genetic subtype of HSP, although wide phenotypic variability within the same genetic subtype and also within the same family can be found.

  5. Cognitive dysfunction in adult patients with neuromyelitis optica: a systematic review and meta-analysis.

    Science.gov (United States)

    Meng, Hao; Xu, Jun; Pan, Chenling; Cheng, Jiaxing; Hu, Yue; Hong, Yin; Shen, Yuehai; Dai, Hua

    2017-08-01

    The objective of this study was to investigate cognitive dysfunction in 24-60-year-old neuromyelitis optica (NMO) patients, demographically matched healthy subjects, and MS patients. We conducted a comprehensive literature review of the PubMed, Medline, EMBASE, CNKI, Wan Fang Date, Web of Science, and Cochrane Library databases from inception to May 2016 for case-control studies that reported cognitive test scores in NMO patients, healthy subjects, and MS patients. Outcome measures were cognitive function evaluations, including performance on attention, language, memory, information processing speed, and executive function tests. The meta-analysis included eight studies. NMO patients performed significantly worse on attention (P < 0.00001), language (P = 0.00008), memory (P = 0.00004), information processing speed (P < 0.00001), and executive function tests (P = 0.00009) than healthy subjects. There were no significant differences in performance between NMO patients and MS patients on these tests. This meta-analysis indicates that NMO patients aged 24-60 years have significantly worse cognitive performance than demographically matched healthy subjects. However, this was comparable to the performance of demographically matched MS patients. There is a need for further rigorous randomized controlled trials with focus on elucidating the underlying mechanism of cognitive dysfunction in NMO patients.

  6. Dysfunctional beliefs in group and individual cognitive behavioral therapy for obsessive compulsive disorder

    DEFF Research Database (Denmark)

    Jónsson, Hjalti; Hougaard, Esben; Bennedsen, Birgit

    2011-01-01

    The primary aim of the study was to investigate dysfunctional beliefs in the form of inflated responsibility (IR) and thought action fusion (TAF) as predictive and mediating variables in Individual (n = 33) and Group (n = 37) Cognitive Behavioral Therapy (CBT) for Obsessive Compulsive Disorder (OCD...... of the study with pre-and post-therapy measurements only does not allow for a causal mediator analysis...

  7. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

    Directory of Open Access Journals (Sweden)

    Iveta Bernatova

    2014-01-01

    Full Text Available Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP. The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (prehypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

  8. The Effects of Antioxidants and Experience on the Development of Age Dependent Cognitive Dysfunction and Neuropathology in Canines

    National Research Council Canada - National Science Library

    Muggenburg, Bruce

    2001-01-01

    Progression of individual rates of age-dependent cognitive dysfunction and the potential for antioxidants and environmental enrichment to slow the rate of decline are being evaluated over a 3-year span in beagle dogs...

  9. The Effects of Antioxidants and Experience on the Development of Age Dependent Cognitive Dysfunction and Neuropathology in Canines

    National Research Council Canada - National Science Library

    Muggenburg, Bruce

    2002-01-01

    Progression of individual rates of age-dependent cognitive dysfunction and the potential for antioxidants and environmental enrichment to slow the rate of decline are being evaluated over a 3-year span in beagle dogs...

  10. The Effects of Antioxidants and Experience on the Development of Age Dependent Cognitive Dysfunction and Neuropathology in Canines

    National Research Council Canada - National Science Library

    Muggenburg, Bruce

    2003-01-01

    Progression of individual rates of age-dependent cognitive dysfunction and the potential for antioxidants and environmental enrichment to slow the rate of decline are being evaluated over a 3-year span in beagle dogs...

  11. [Does an association between increased homocystein levels and cognitive dysfunction also exist in multimorbid geriatric patients].

    Science.gov (United States)

    Hengstermann, S; Hanemann, A; Nieczaj, R; Abdollahnia, N; Schweter, A; Steinhagen-Thiessen, E; Lun, A; Lämmler, G; Schulz, R-J

    2009-04-01

    Total blood homocysteine (Hcys) and folate have been investigated in association with cognitive dysfunction (CD) in healthy but not in multimorbid elderly patients. We hypothesized that total Hcys and folate are adequate markers to identify multimorbid elderly patients with CD. According to the Short Performance Cognitive Test (SKT) CD was determined in a cross-sectional study with 189 (131 f/58 m) multimorbid elderly patients with a mean age of 78.6 +/- 7.3 yrs. Besides the analyses of biochemical parameters (Hcys, folate, vitamin B(12), hemogram) nutritional status (BMI, Mini Nutritional Assessment) as well as activities of daily living were assessed. Daily nutritional intake was measured with a 3-day nutrition diary. For analysis, we used the nutritional software program DGE-PC professional. According to SKT 25.4% showed no cerebral cognitive dysfunction, 21.2% had a suspicion about incipient cognitive dysfunction, 12.7% showed mild, 9.0% moderate, 31.7% of patients severe cognitive deficits. Median plasma Hcys was about 20% elevated in multimorbid elderly patients independent of CD. Serum folate and vitamin B(12) levels were within range, though dietary folate intake (97 [80-128] microg/d) was reduced about 75% (recommendation 400 microg/d). Significant correlations between vitamin intake and plasma/serum levels of Hcys, folate and vitamin B(12) were not present. We did not find significant differences between SKT groups of nutritional status, activities of daily living, index of diseases, medications, or selected biochemical parameters. We analysed elevated serum Hcys levels in multimorbid elderly patients with normal plasma folate and vitamin B(12) concentration and CD. Plasma Hcys or serum folate did not appear as an important biological risk factor on CD in multimorbid elderly patients.

  12. Coping with cancer-related cognitive dysfunction: a scoping review of the literature.

    Science.gov (United States)

    Sleight, Alix

    2016-01-01

    Cancer-related cognitive dysfunction (CRCD) impacts memory, attention, concentration, language, multi-tasking, and organizational skills and decreases participation and quality of life for cancer survivors. The objectives of this article are: (1) to outline the neuroscience of CRCD, its risk factors, and its effect on participation; and (2) to identify and summarize the literature on rehabilitation interventions and coping techniques for CRCD in cancer survivors. A scoping review of articles cited in PubMed, MEDLINE, PsychINFO, and CINAHL was performed. To be included, articles must have been published in a peer-reviewed scientific journal between 1996 and 2014, written in English, and included a quantitative or qualitative non-pharmacological study of interventions and/or coping strategies for adult cancer survivors experiencing CRCD. Ten articles met the inclusion criteria for final review. Six studies tested the efficacy of rehabilitation treatments on CRCD. Three involved cognitive-behavioral therapy (CBT), while three tested neuropsychological and/or cognitive training interventions. Four qualitative studies investigated coping strategies used by survivors with CRCD. CBT-based treatments and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most commonly-reported coping strategy is utilization of assistive technology and memory aids. Further research is needed about efficacious rehabilitation techniques for this population. Implications for Rehabilitation Cancer-related cognitive dysfunction (CRCD) may impact up to 50% of cancer survivors. CRCD can significantly decrease participation and quality of life during survivorship. Cognitive-behavioral therapy (CBT) and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most common coping strategy reported by cancer survivors with CRCD is the use of assistive technology and memory aids.

  13. Integrating psychopharmacology and cognitive remediation to treat cognitive dysfunction in the psychotic disorders.

    Science.gov (United States)

    Medalia, Alice; Opler, Lewis A; Saperstein, Alice M

    2014-04-01

    Cognitive deficits are a prominent and enduring aspect of schizophrenia, which pose a significant barrier to achieving functional goals. The most promising intervention for treating cognitive impairment is cognitive remediation (CR), a behaviorally based therapy associated with medium effect sizes for cognitive and functional outcomes. However, there is a sizeable group of nonresponders whose CR outcomes become limited when the therapeutic approach fails to address individual differences in baseline cognition, motivation variables, and the extent to which CR offers opportunities for generalization. This speaks to a need to develop cognitive interventions that are both personalized and scalable. Emerging data suggest that specific pharmacological agents have the potential to enhance and accelerate behaviorally based CR effects. This article will review the rationale and preliminary evidence to support combining CR and pharmacotherapy. We will review crucial aspects of cognitive interventions that offer the most promise for improving not only cognitive outcomes, but also for enhancing improvement in real-world functioning. Finally, we will address methodological issues to be considered for future research on combined pharmacological and CR interventions.

  14. Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

    Science.gov (United States)

    Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

    2013-01-01

    Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

  15. The Effect of Cognitive-Behavioral Counseling on Anxiety and Aggression Women with Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    P Nemati

    2013-05-01

    Full Text Available Abstract Background and aim: According to the American Psychiatric Association female sexual dysfunction are classified in four categories: sexual desire disorders, arousal, orgasm and pain. Having chronic Sexual dysfunction can lead to anxiety, depression, aggression and create problems in other aspects of life. The aim of this study was to Investigate the effect of cognitive-behavior counseling on anxiety and aggression in women with sexual dysfunction. Methods: In this clinical trial, 20 women were referred to Taleghani Hospital in Tehran with anxiety and aggression of sexual problems selected to measure sexual satisfaction. Glombok Rust questionnaire was used to measured the sexual satisfaction and Spielberger Questionnaire 40-item for Anxiety and Buss and Mark Perry questionnaire for aggression. Data were statistically analyzed by t test. Results: in general, the mean total of sexual satisfaction decreased from 79.05 at pretest to 7.35 at posttest p <0.05. the mean pretest of physical aggression from 28.2 and verbal aggression from 17.3 and nervous aggression from 28.95 followed by the aggression of the enemy from 29.95, have declined in post test to 12. 55 , 7.8, 12.3, and 3/12 respectively ( p <0.05. the results of Spielberger questionnaire showed that the mean pre-test state and trait anxiety were decreased from 63 and 62.5 to 35.1 and 34.15 respectively (p <0.05. Conclusion: Cognitive-behavioral counseling may not only have a significant effect in reducing sexual dysfunction in women, but also a significant role in reducing anxiety and aggression as reactions with this disorder. Key words: Sexual Dysfunction, Anxiety, Aggression, Women

  16. A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

    Science.gov (United States)

    Kiehl, Kent A

    2006-06-15

    Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

  17. Acute cognitive dysfunction after hip fracture: frequency and risk factors in an optimized, multimodal, rehabilitation program

    DEFF Research Database (Denmark)

    Bitsch, Martin; Foss, Nicolai Bang; Kristensen, Billy Bjarne

    2006-01-01

    hip fracture surgery in an optimized, multimodal, peri-operative rehabilitation regimen. METHODS: One hundred unselected hip fracture patients treated in a well-defined, optimized, multimodal, peri-operative rehabilitation regimen were included. Patients were tested upon admission and on the second......BACKGROUND: Patients undergoing hip fracture surgery often experience acute post-operative cognitive dysfunction (APOCD). The pathogenesis of APOCD is probably multifactorial, and no single intervention has been successful in its prevention. No studies have investigated the incidence of APOCD after......, fourth and seventh post-operative days with the Mini Mental State Examination (MMSE) score. RESULTS: Thirty-two per cent of patients developed a significant post-operative cognitive decline, which was associated with several pre-fracture patient characteristics, including age and cognitive function...

  18. Oxidized CaMKII causes cardiac sinus node dysfunction in mice

    OpenAIRE

    Swaminathan, Paari Dominic; Purohit, Anil; Soni, Siddarth; Voigt, Niels; Singh, Madhu V.; Glukhov, Alexey V.; Gao, Zhan; He, B. Julie; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Kutschke, William; Yang, Jinying; Donahue, J. Kevin; Weiss, Robert M.; Grumbach, Isabella M.

    2011-01-01

    Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomark...

  19. Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis.

    Science.gov (United States)

    Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

    2017-01-01

    Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

  20. Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis

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    Mario Stampanoni Bassi

    2017-11-01

    Full Text Available Cognitive deficits are frequently observed in multiple sclerosis (MS, mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ1–42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β, IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα, interferon γ (IFNγ in the cerebrospinal fluid (CSF of 103 remitting MS patients. CSF levels of Aβ1–42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra. Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

  1. Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

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    Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

    2013-01-01

    Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD

  2. Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

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    Samuel J Bolitho

    Full Text Available INTRODUCTION: Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. METHODS: Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. RESULTS: Patients with PD had a 225% increase in the mean nap time per day (minutes as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001. Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. CONCLUSION: This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime

  3. Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

    Science.gov (United States)

    Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

    2013-01-01

    Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of

  4. The consequence of spatial visual processing dysfunction caused by traumatic brain injury (TBI).

    Science.gov (United States)

    Padula, William V; Capo-Aponte, Jose E; Padula, William V; Singman, Eric L; Jenness, Jonathan

    2017-01-01

    A bi-modal visual processing model is supported by research to affect dysfunction following a traumatic brain injury (TBI). TBI causes dysfunction of visual processing affecting binocularity, spatial orientation, posture and balance. Research demonstrates that prescription of prisms influence the plasticity between spatial visual processing and motor-sensory systems improving visual processing and reducing symptoms following a TBI. The rationale demonstrates that visual processing underlies the functional aspects of binocularity, balance and posture. The bi-modal visual process maintains plasticity for efficiency. Compromise causes Post Trauma Vision Syndrome (PTVS) and Visual Midline Shift Syndrome (VMSS). Rehabilitation through use of lenses, prisms and sectoral occlusion has inter-professional implications in rehabilitation affecting the plasticity of the bi-modal visual process, thereby improving binocularity, spatial orientation, posture and balance Main outcomes: This review provides an opportunity to create a new perspective of the consequences of TBI on visual processing and the symptoms that are often caused by trauma. It also serves to provide a perspective of visual processing dysfunction that has potential for developing new approaches of rehabilitation. Understanding vision as a bi-modal process facilitates a new perspective of visual processing and the potentials for rehabilitation following a concussion, brain injury or other neurological events.

  5. The general movement assessment helps us to identify preterm infants at risk for cognitive dysfunction

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    Christa eEinspieler

    2016-03-01

    Full Text Available Apart from motor and behavioral dysfunctions, deficits in cognitive skills are among the well-documented sequelae of preterm birth. However, early identification of infants at risk for poor cognition is still a challenge, as no clear association between pathological findings based on neuroimaging scans and cognitive functions have been detected as yet. The Prechtl General Movement Assessment (GMA has shown its merits for the evaluation of the integrity of the young nervous system. It is a reliable tool for identifying infants at risk for neuromotor deficits. Recent studies on preterm infants demonstrate that abnormal general movements also reflect impairments of brain areas involved in cognitive development. The aim of this systematic review was to discuss studies that included (i the Prechtl GMA applied in preterm infants, and (ii cognitive outcome measures in six data bases. Seven studies met the inclusion criteria and yielded the following results: (a children born preterm with consistently abnormal general movements up to 8 weeks after term had lower intelligence quotients at school age than children with an early normalization of general movements; (b from 3 to 5 months after term, several qualitative and quantitative aspects of the concurrent motor repertoire, including postural patterns, were predictive of intelligence at 7 to 10 years of age. These findings in 428 individuals born preterm suggest that normal general movements along with a normal motor repertoire during the first months after term are markers for normal cognitive development until at least age 10.

  6. Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

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    Mak Adam Daulatzai

    2012-01-01

    Full Text Available OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS is the central integration hub for afferents from upper airway (somatosensory/gustatory, respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges.

  7. Thinking through postoperative cognitive dysfunction : How to bridge the gap between clinical and pre-clinical perspectives

    NARCIS (Netherlands)

    Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Heineman, Erik; Izaks, Gerbrand J.; van Leeuwen, Barbara L.

    2012-01-01

    Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a

  8. The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

    Science.gov (United States)

    Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

    2016-06-01

    Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

  9. Nocturnal hypoxia in ALS is related to cognitive dysfunction and can occur as clusters of desaturations.

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    Su-Yeon Park

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night and their clinical characteristics and cognitive function were compared.Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40% had poor memory retention (p = 0.039 and retrieval efficiency (p = 0.045. A cluster-of-desaturation pattern was identified in 7 patients (70% in the Hypoxia Group.These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation-reoxygenation (a cluster-of-desaturation pattern during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.

  10. THE EFFECTS OF COGNITIVE DYSFUNCTIONS ON THE ELDERLY PATIENTS WITH LOW BACK PAIN

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    Chiriţi Gheorghe

    2012-09-01

    Full Text Available The aim of this study is to estimate the importance of the mental factor in the functional regression of the elder patient, alongside the usual evaluation of the musculoskeletal system (assessment of joints, muscle testing, functional assessment a psychological examination is needed which enables the accurate evaluation of the state of the cognitive functions. If these functions are intact, we can state that the functional regression is exclusively due to the decompensation of the musculoskeletal system, and the physical and kinetic treatment applied according to the classic methodology shall be sufficient and efficient for the functional recovery. However, if the cognitive functions are deteriorated, even in the slightest amount, the same recovery method is inefficient to help the patient regain his prior autonomy.The aim of this study is to emphasize the negative effects of cognitive disorders, depression and anxiety in the evolution of pain, physical dysfunction, disabilities, drug intake and quality of life.The efficiency of the rehabilitation program for elderly with low back pain in improving the pain, the physical dysfunction, disabilities, drug intake and quality of life depending on the psycho-sensorial compliance.

  11. Bihemispheric cerebral FDG PET correlates of cognitive dysfunction as assessed by the CERAD in Alzheimer's disease.

    Science.gov (United States)

    Schönknecht, Oskar Dieter Peter; Hunt, Aoife; Toro, Pablo; Guenther, Thomas; Henze, Marcus; Haberkorn, Uwe; Schröder, Johannes

    2011-04-01

    Alzheimer's disease (AD) is characterized by a variety of cognitive deficits which can be reliably assessed by the neuropsychological test battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), but the cerebral changes underlying the respective cognitive deficits are only partly understood. Measures of severity of dementia in AD as well as delayed episodic memory performance in mild cognitive impairment significantly correlated with bihemispheric cerebral glucose hypometabolism. We therefore hypothesized that the CERAD cognitive battery may represent cerebral dysfunction of both hemispheres in patients with AD. In 32 patients with AD, cerebral glucose metabolism was investigated using positron-emission-tomography with 18Fluorodeoxyglucose (FDG PET) and associated with the test scores of the CERAD cognitive battery by statistical parametric mapping. Episodic memory scores significantly correlated with temporopari etal glucose metabolism of both hemispheres while delayed episodic memory significantly was correlated with the right frontotemporal cortices. Verbal fluency and naming scores significantly correlated with glucose metabolism in left temporoparietal and right frontal cortices, whereas constructional praxis predominantly correlated significantly with the bilateral precuneus. In conclusion, the results of our study demonstrate that not only memory function but also functions of language and constructional praxis in AD are associated with glucose metabolism as revealed by FDG PET in subsets of uni- and bilateral brain areas. The findings of our study for the first time demonstrate that in AD neuropsychological deficits as assessed by the CERAD refer to different cerebral sites of both hemispheres.

  12. New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function.

    Science.gov (United States)

    Uehara, Takashi; Sumiyoshi, Tomiki; Kurachi, Masayoshi

    2015-01-01

    Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia.

  13. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

    Science.gov (United States)

    Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A

    2017-02-01

    Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response

  14. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

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    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-08-01

    Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

  15. Recurrent pannus formation causing prosthetic aortic valve dysfunction: Is excision without valve re-replacement applicable?

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    Darwazah Ahmad K

    2012-06-01

    Full Text Available Abstract Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function. The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replacement. A recurrent pannus was observed in a female patient who needed repeated surgical intervention to excise a localized pannus without re-replacement of a well functioning prosthetic valve. Management of our case presents several questions, whether recurrence of pannus is caused by sparing the prosthetic valve, is it simply an exaggeration of an inflammatory healing process in certain individuals or is it ideal to re-replace the valve despite a well preserved function.

  16. Recurrent pannus formation causing prosthetic aortic valve dysfunction: is excision without valve re-replacement applicable?

    Science.gov (United States)

    Darwazah, Ahmad K

    2012-06-29

    Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function.The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replacement.A recurrent pannus was observed in a female patient who needed repeated surgical intervention to excise a localized pannus without re-replacement of a well functioning prosthetic valve.Management of our case presents several questions, whether recurrence of pannus is caused by sparing the prosthetic valve, is it simply an exaggeration of an inflammatory healing process in certain individuals or is it ideal to re-replace the valve despite a well preserved function.

  17. Genetic variation and cognitive dysfunction in opioid-treated patients with cancer

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Ekholm, Ola; Kaasa, Stein

    2016-01-01

    of 10% for determining associations (Benjamini-Hochberg method). Co-dominant, dominant, and recessive models were analyzed by Kruskal-Wallis and Mann-Whitney tests. RESULTS: In the co-dominant model significant associations (P ... by Mini-Mental State Examination (MMSE). ANALYSES: SNPs were rejected if violation of Hardy-Weinberg equilibrium (P test); false discovery rate...... sample. After correction for multiple testing, no SNPs were significant in the discovery sample. Dominant and recessive models also did not confirm significant associations. CONCLUSIONS: The findings did not support influence of those SNPs analyzed to explain cognitive dysfunction in opioid...

  18. Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

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    G. Olivito

    2017-01-01

    In the present study, the network-based statistics (NBS approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes.

  19. Executive cognitive dysfunction and ADHD in cocaine dependence: searching for a common cognitive endophenotype for addictive disorders

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    Paulo Jannuzzi Cunha

    2013-10-01

    Full Text Available Background: Cocaine dependent individuals (CDI present executive cognitive function (ECF deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI+ADHD would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI. Methods: we evaluated 101 adults, including 69 cocaine dependent subjects and 32 controls. ECF domains were assessed with Digits Forward (DF, Digits Backward (DB, Stroop Color Word Test (SCWT, the Wisconsin Card Sorting Test (WCST, and the Frontal Assessment Battery (FAB. DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood were retrospectively assessed by the Wender-Utah Rating Scale (WURS. Results: there were no significant differences between CDI+ADHD, CDI and controls in estimated IQ, socioeconomic background, education (in years and premorbid IQ (p>0.05. SCWT and WCST scores did not differ across groups. Nevertheless, CDI and CDI+ADHD performed more poorly than controls in total score of the FAB. Also, CDI+ADHD did worse than CDI on DF, DB, Conceptualization/FAB, and Mental flexibility/FAB. We did not find correlations between cocaine use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p=0.016 and with the total score of the FAB. Conclusion: CDI+TDAH presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on executive dysfunction in CDI. It remains to be investigated by future studies if symptoms such as impulsivity or a pre-existing ECF dysfunction could represent underlying cognitive endophenotypes that would substantially increase the risk for acquiring addictive disorders.

  20. Screening for cognitive dysfunction in Huntington's disease with the clock drawing test.

    Science.gov (United States)

    Terwindt, Paul W; Hubers, Anna A M; Giltay, Erik J; van der Mast, Rose C; van Duijn, Erik

    2016-09-01

    The aim of the study is to investigate the performance of the clock drawing test as a screening tool for cognitive impairment in Huntington's disease (HD) mutation carriers. The performance of the clock drawing test was assessed in 65 mutation carriers using the Shulman and the Freund scoring systems. The mini-mental state examination, the Symbol Digit Modalities Test, the Verbal Fluency Test, and the Stroop tests were used as comparisons for the evaluation of cognitive functioning. Correlations of the clock drawing test with various cognitive tests (convergent validity), neuropsychiatric characteristics (divergent validity) and clinical characteristics were analysed using the Spearman's rank correlation coefficient. Receiver-operator characteristic analyses were performed for the clock drawing test against both the mini-mental state examination and against a composite variable for executive cognitive functioning to assess optimal cut-off scores. Inter-rater reliability was high for both the Shulman and Freund scoring systems (ICC = 0.95 and ICC = 0.90 respectively). The clock drawing tests showed moderate to high correlations with the composite variable for executive cognitive functioning (mean ρ = 0.75) and weaker correlations with the mini-mental state examination (mean ρ = 0.62). Mean sensitivity of the clock drawing tests was 0.82 and mean specificity was 0.79, whereas the mean positive predictive value was 0.66 and the mean negative predictive value was 0.87. The clock drawing test is a suitable screening instrument for cognitive dysfunction in HD, because it was shown to be accurate, particularly so with respect to executive cognitive functioning, and is easy and quick to use. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Mismatch Negativity as an Indicator of Cognitive Sub-Domain Dysfunction in Amyotrophic Lateral Sclerosis

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    Parameswaran Mahadeva Iyer

    2017-08-01

    Full Text Available ObjectiveTo evaluate the utility of mismatch negativity (MMN, a neurophysiologic marker of non-motor cognitive processing, in amyotrophic lateral sclerosis (ALS.Methods89 patients, stratified into 4 different phenotypic presentations of ALS (67 spinal-onset, 15 bulbar-onset, 7 ALS-FTD, 7 C9ORF72 gene careers, and 19 matched controls underwent 128-channel EEG data recording. Subjects were presented with standard auditory tones interleaved with pitch-deviant tones in three recording blocks. The MMN response was quantified by peak amplitude, peak delay, average amplitude, and average delay, 100–300 ms after stimuli. 64 patients underwent cognitive screening using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS, and 38 participants underwent contemporaneous cognitive assessment using the Stroop Color–Word Interference test (CWIT, which measures attention shift, inhibitory control, and error monitoring.ResultsThe MMN response was observed in frontal and frontocentral regions of patient and control groups. Compared to controls, waveforms were attenuated in early onset, and the average delay was significantly increased in all of the ALS subgroups, with no significant difference between subgroups. Comparing with the control response, the ALS MMN response clustered into four new subgroups characterized by differences in response latency. The increased average delay correlated with changes in the Stroop CWIT; however, it did not show a direct relationship with age, gender, traditional phenotypes, revised ALS Functional Rating Scale, or ECAS scores.Conclusion and significanceThe MMN response in ALS patients reflects the cognitive dysfunction in specific sub-domains, as the new patient subgroups, identified by cluster analysis, do not segregate with existing clinical or cognitive classifications. Event-related potentials can provide additional quantitative neurophysiologic measures of impairment in specific cognitive sub-domains from which it

  2. Cognitive dysfunction in patients with brain metastases: influences on caregiver resilience and coping.

    Science.gov (United States)

    Saria, Marlon Garzo; Courchesne, Natasia; Evangelista, Lorraine; Carter, Joshua; MacManus, Daniel A; Gorman, Mary Kay; Nyamathi, Adeline M; Phillips, Linda R; Piccioni, David; Kesari, Santosh; Maliski, Sally

    2017-04-01

    Neurologic deficits that may be manifested as cognitive impairment contribute to the challenges faced by caregivers of patients with brain metastases. To better address their needs, we examined how caregivers respond to these challenges and explore the relationship between the patient's cognitive impairment and caregiver resilience and coping. We conducted a descriptive, cross-sectional study using self-reported data from 56 caregivers of patients with brain metastases. Study participants from a comprehensive cancer center were asked to complete a series of instruments that measured their perception of the patient's cognitive dysfunction (revised memory and behavior problems checklist, RMBC), their own personal resilience (Resilience Scale, RS), and their utilization of a broad range of coping responses (COPE inventory and Emotional-Approach Coping scale). Caregivers reported that memory-related problems occurred more frequently in the patients they cared for compared to depression and disruptive behavior (mean scores 3.52 vs 2.34 vs. 1.32, respectively). Coping strategies most frequently used by caregivers were acceptance (3.28), planning (3.08), and positive reinterpretation and growth (2.95). Most caregivers scored moderate to high on the RS (77%). The coping strategy acceptance correlated significantly with the memory and disruptive behavior subscales of the RMBC. Given the protective effect of problem-focused coping and the high rate of caregivers utilizing less effective coping strategies in instances of worsening cognitive dysfunction, healthcare professionals need to systematically assess the coping strategies of caregivers and deliver a more personalized approach to enhance effective coping among caregivers of patients with brain metastases.

  3. Cigarette Smoke-Induced Cell Death Causes Persistent Olfactory Dysfunction in Aged Mice

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    Rumi Ueha

    2018-06-01

    Full Text Available Introduction: Exposure to cigarette smoke is a cause of olfactory dysfunction. We previously reported that in young mice, cigarette smoke damaged olfactory progenitors and decreased mature olfactory receptor neurons (ORNs, then, mature ORNs gradually recovered after smoking cessation. However, in aged populations, the target cells in ORNs by cigarette smoke, the underlying molecular mechanisms by which cigarette smoke impairs the regenerative ORNs, and the degree of ORN regeneration after smoking cessation remain unclear.Objectives: To explore the effects of cigarette smoke on the ORN cell system using an aged mouse model of smoking, and to investigate the extent to which smoke-induced damage to ORNs recovers following cessation of exposure to cigarette smoke in aged mice.Methods: We intranasally administered a cigarette smoke solution (CSS to 16-month-old male mice over 24 days, then examined ORN existence, cell survival, changes of inflammatory cytokines in the olfactory epithelium (OE, and olfaction using histological analyses, gene analyses and olfactory habituation/dishabituation tests.Results: CSS administration reduced the number of mature ORNs in the OE and induced olfactory dysfunction. These changes coincided with an increase in the number of apoptotic cells and Tumor necrosis factor (TNF expression and a decrease in Il6 expression. Notably, the reduction in mature ORNs did not recover even on day 28 after cessation of treatment with CSS, resulting in persistent olfactory dysfunction.Conclusion: In aged mice, by increasing ORN death, CSS exposure could eventually overwhelm the regenerative capacity of the OE, resulting in continued reduction in the number of mature ORNs and olfactory dysfunction.

  4. Whole-food diet worsened cognitive dysfunction in an Alzheimer's disease mouse model.

    Science.gov (United States)

    Parrott, Matthew D; Winocur, Gordon; Bazinet, Richard P; Ma, David W L; Greenwood, Carol E

    2015-01-01

    Food combinations have been associated with lower incidence of Alzheimer's disease. We hypothesized that a combination whole-food diet containing freeze-dried fish, vegetables, and fruits would improve cognitive function in TgCRND8 mice by modulating brain insulin signaling and neuroinflammation. Cognitive function was assessed by a comprehensive battery of tasks adapted to the Morris water maze. Unexpectedly, a "Diet × Transgene" interaction was observed in which transgenic animals fed the whole-food diet exhibited even worse cognitive function than their transgenic counterparts fed the control diet on tests of spatial memory (p < 0.01) and strategic rule learning (p = 0.034). These behavioral deficits coincided with higher hippocampal gene expression of tumor necrosis factor-α (p = 0.013). There were no differences in cortical amyloid-β peptide species according to diet. These results indicate that a dietary profile identified from epidemiologic studies exacerbated cognitive dysfunction and neuroinflammation in a mouse model of familial Alzheimer's disease. We suggest that normally adaptive cellular responses to dietary phytochemicals were impaired by amyloid-beta deposition leading to increased oxidative stress, neuroinflammation, and behavioral deficits. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

    Science.gov (United States)

    Santamaría-García, Hernando; Santangelo, Gabriella

    2018-01-01

    Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

  6. Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Foteini Christidi

    2018-01-01

    Full Text Available Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM, emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs, most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients’ management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD, or may emerge during the disease course as critical aspects, such as for Parkinson’s and Alzheimer’s diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients’ well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

  7. Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy.

    Science.gov (United States)

    Sussman, Eric S; Kellner, Christopher P; Mergeche, Joanna L; Bruce, Samuel S; McDowell, Michael M; Heyer, Eric J; Connolly, E Sander

    2014-09-01

    Approximately 25% of patients exhibit cognitive dysfunction 24 hours after carotid endarterectomy (CEA). One of the purported mechanisms of early cognitive dysfunction (eCD) is hypoperfusion due to inadequate collateral circulation during cross-clamping of the carotid artery. The authors assessed whether poor collateral circulation within the circle of Willis, as determined by preoperative CT angiography (CTA) or MR angiography (MRA), could predict eCD. Patients who underwent CEA after preoperative MRA or CTA imaging and full neuropsychometric evaluation were included in this study (n = 42); 4 patients were excluded due to intraoperative electroencephalographic changes and subsequent shunt placement. Thirty-eight patients were included in the statistical analyses. Patients were stratified according to posterior communicating artery (PCoA) status (radiographic visualization of at least 1 PCoA vs of no PCoAs). Variables with p PCoAs was the only independent predictor of eCD (OR 9.64, 95% CI 1.43-64.92, p = 0.02). The absence of both PCoAs on preoperative radiographic imaging is predictive of eCD after CEA. This finding supports the evidence for an underlying ischemic etiology of eCD. Larger studies are justified to verify the findings of this study. Clinical trial registration no.: NCT00597883 ( http://www.clinicaltrials.gov ).

  8. Cerebral Mast Cells Participate In Postoperative Cognitive Dysfunction by Promoting Astrocyte Activation.

    Science.gov (United States)

    Zhang, Xiang; Yao, Hao; Qian, Qingqing; Li, Nana; Jin, Wenjie; Qian, Yanning

    2016-01-01

    Astrocytes, the major glial cell type that has been increasingly recognized as contributing to neuroinflammation, are critical in the occurrence and development of postoperative cognitive dysfunction (POCD). Although emerging evidence showed that brain mast cells (MCs) are the "first responders" in neuroinflammation, little is known about the functional communication between MCs and astrocytes. In this study, we investigated the potential regulation of astrocyte activation by MCs. Rats received an intracerebroventricular injection of Cromolyn (an MC stabilizer) or sterile saline 30 min before undergoing open tibial fracture surgery, and the levels of neuroinflammation and the degree of memory dysfunction were evaluated at 1 day and 3 days after surgery. In the in vitro study, the effect of activated MCs on astrocytes were further clarified. Surgery increased the number of MCs, the astrocyte activation and the production of inflammatory factors, and resulted in cognitive deficits. Site-directed pre-injection of Cromolyn can inhibit this effect. In the vitro study, the conditioned medium from C48/80-stimulated mast cells (P815) could induce primary astrocyte activation and subsequent production of inflammatory cytokines, which could be inhibited by Cromolyn. These findings indicate that activated MCs could trigger astrocyte activation, be involved in neuroinflammation and possibly contribute to POCD. Interactions between MCs and astrocytes could provide potential therapeutic targets for POCD. © 2016 The Author(s) Published by S. Karger AG, Basel.

  9. Cerebral Mast Cells Participate In Postoperative Cognitive Dysfunction by Promoting Astrocyte Activation

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    2016-11-01

    Full Text Available Background: Astrocytes, the major glial cell type that has been increasingly recognized as contributing to neuroinflammation, are critical in the occurrence and development of postoperative cognitive dysfunction (POCD. Although emerging evidence showed that brain mast cells (MCs are the "first responders” in neuroinflammation, little is known about the functional communication between MCs and astrocytes. Methods: In this study, we investigated the potential regulation of astrocyte activation by MCs. Rats received an intracerebroventricular injection of Cromolyn (an MC stabilizer or sterile saline 30 min before undergoing open tibial fracture surgery, and the levels of neuroinflammation and the degree of memory dysfunction were evaluated at 1 day and 3 days after surgery. In the in vitro study, the effect of activated MCs on astrocytes were further clarified. Results: Surgery increased the number of MCs, the astrocyte activation and the production of inflammatory factors, and resulted in cognitive deficits. Site-directed pre-injection of Cromolyn can inhibit this effect. In the vitro study, the conditioned medium from C48/80-stimulated mast cells (P815 could induce primary astrocyte activation and subsequent production of inflammatory cytokines, which could be inhibited by Cromolyn. Conclusion: These findings indicate that activated MCs could trigger astrocyte activation, be involved in neuroinflammation and possibly contribute to POCD. Interactions between MCs and astrocytes could provide potential therapeutic targets for POCD.

  10. Neuroticism in child sex offenders and its association with sexual dysfunctions, cognitive distortions, and psychological complaints.

    Science.gov (United States)

    Boillat, Coralie; Deuring, Gunnar; Pflueger, Marlon O; Graf, Marc; Rosburg, Timm

    Studies in child sex offenders (CSO) often report deviant personality characteristics. In our study, we investigated neuroticism in CSO and tested the hypothesis that CSO with high neuroticism show more serious abuse behavior and are more likely to exhibit sexual dysfunction and cognitive distortions, as compared to CSO with low neuroticism. A sample of 40 CSO (both child sexual abusers and child sexual material users) was split into two subsamples based on their neuroticism scores, obtained by the NEO-Personality Inventory-Revised (NEO-PI-R) questionnaire. Subsequently, we compared their scores in the Multiphasic Sex Inventory (MSI) questionnaire and Symptom Checklist-90-Revised (SCL-90-R). Our results show that CSO exhibited higher levels of neuroticism than controls, but were still in the normal range. In CSO, neuroticism was associated with sexual dysfunction and cognitive distortions, rather than with more severe abuse behavior. Moreover, neuroticism in this group was linked to a broad range of psychological problems and psychopathological symptoms, such as somatization or anxiety. Our findings suggest that neuroticism even below the level of personality disorder is associated with a broader range of psychological problems in CSO, which should be addressed in therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. ROLE OF NEUROSPECIFIC PROTEINS IN THE DEVELOPMENT OF COGNITIVE DYSFUNCTION IN PATIENTS WITH TYPE 1 DIABETES

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    M. V. Novosyolova

    2014-01-01

    Full Text Available Type 1 (type 1 DM diabetes mellitus is one of the common chronic metabolic diseases, which currently is a significant problem due to disability at a young age and reduce life expectancy. Despite the fact that type 1 diabetes accounts for only 10% of all patients with diabetes, it occurs particularly hard, with a tendency to progression. One of the targets of type 1 diabetes is the central nervous system with the further formation of cognitive dysfunction in young age leads to diminished quality of life. Cognitive deficits may be the result not only of structural lesions of the brain, but it may be due to the development of metabolic disorders. In the case of timely diagnosis and treatment of cognitive impairment associated with metabolic changes that can partially or completely regress. The aim of this study was to identify biomarkers of the brain damage in young patients with type 1 diabetes. The study involved 58 patients with  type  1  diabetes,  the  control  group  comprised  29  healthy  controls.  The  complex  included a neuropsychological examination which was used for testing the Montreal scale (MoCA test rapid screening of cognitive impairment, assessment of quality of life using a common questionnaire Medical Outcomes Study Short Form (MOS SF-36 and the specific audit – dependent quality of life (ADDQoL. To evaluateearly markersin the developmentof cognitive dysfunctionwere identifiedneurospecific proteins – S100 protein and glial fibrillary acidic protein (GFAP, myelin basic protein (MBP. Found an increased level of neurospecific protein that was correlated with parameters of carbohydrate metabolism, poor quality of life and severe cognitive deficiency (MoCA test lower than 26 points.

  12. The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese Patients with Multiple System Atrophy.

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    Bei Cao

    Full Text Available Studies on cognition in multiple system atrophy (MSA patients are limited.A total of 110 MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R, Frontal Assessment Battery (FAB, Frontal Behavioral Inventory (FBI, and Unified MSA Rating Scale (UMSARS tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales.Approximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%, followed by memory (24.5%, language (20% and orientation/attention (20% based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9% as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2% showed moderate frontal behavior changes (FBI score 4-15, with incontinence (64.5% as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931-60.469, P = 0.001 and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002-5.962, P< 0.049 were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631-11.477, P = 0.003, an education level < 9 years (OR:2.809 95% CI:1.060-7.444, P = 0.038 and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103-13.846, P < 0.0001 were potential determinants of abnormal FAB.Cognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA.

  13. Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction.

    Science.gov (United States)

    Javeed, Naureen; Sagar, Gunisha; Dutta, Shamit K; Smyrk, Thomas C; Lau, Julie S; Bhattacharya, Santanu; Truty, Mark; Petersen, Gloria M; Kaufman, Randal J; Chari, Suresh T; Mukhopadhyay, Debabrata

    2015-04-01

    Pancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer-derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. We characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown. Exosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species. Pancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin(+)/CA19-9(+) exosomes into

  14. Screening for cognitive dysfunction in corticobasal syndrome: utility of Addenbrooke's cognitive examination.

    Science.gov (United States)

    Mathew, Robert; Bak, Thomas H; Hodges, John R

    2011-01-01

    The motor features of corticobasal syndrome (CBS) are well recognized but the fact that many, if not all, affected patients develop cognitive impairment is still underrecognized. The dementia of CBS overlaps most with a language variant of frontotemporal dementia: progressive nonfluent aphasia (PNFA). The aim of this study was to determine the usefulness of Addenbrooke's Cognitive Examination-Revised (ACE-R) in the evaluation of CBS and to document similarities and differences between CBS and PNFA. Patients with well-defined CBS or PNFA from two tertiary referral centers were selected along with matched controls. Twenty-one patients with CBS, 23 patients with PNFA and 47 age- and education- matched controls were included. Both CBS and PNFA groups showed substantial impairment on the ACE-R (f = 17.3-80.2, p < 0.001) and were significantly impaired in all domains (p < 0.001). The only significant difference between CBS and PNFA was in the visuospatial domain (p < 0.009), being worse in CBS. Using a cutoff of 88/89 out of 100, 90% of CBS and 82.6% of PNFA patients were impaired. At this cutoff of 88/89, ACE-R in CBS had sensitivity and specificity values of 91 and 98%, respectively. Copyright © 2011 S. Karger AG, Basel.

  15. Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress.

    Science.gov (United States)

    Tang, Yi-Yun; Wang, Ai-Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

    2018-04-16

    Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H 2 S) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of H 2 S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H 2 S) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of H 2 S in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of H 2 S in Hcy-induced cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study.

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    Fulvia Ceccarelli

    Full Text Available Cognitive impairment (CI has been described in 3-80% of Systemic lupus erythematosus (SLE patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study.We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months at baseline (T0 and after 10 years (T1. A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function was administered. A global cognitive dysfunction score (GCD was obtained and associated with clinical and laboratory features.Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS. This impairment was prevalently mild at T0 (55.5% and mild or moderate at T1 (36.3% for both degrees. After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02, executive functions (P = 0.02 and abstract reasoning (P = 0.03 were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters. Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04 and T1 (r = 0.3; P = 0.03.For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI.

  17. YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction

    DEFF Research Database (Denmark)

    Gabriele, Michele; Vulto-van Silfhout, Anneke T; Germain, Pierre-Luc

    2017-01-01

    that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations. Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin...... on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators....

  18. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl.

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    Daniel T Barratt

    Full Text Available Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468 receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4, cognitive dysfunction (Mini-Mental State Examination ≤ 23, sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111 than wild-type patients (69/325, with a relative risk of 0.45 (95% CI: 0.27 to 0.76 when accounting for major non-genetic predictors (age, Karnofsky functional score. This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.

  19. Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy

    NARCIS (Netherlands)

    van Duinkerken, Eelco; Ijzerman, Richard G.; Klein, Martin; Moll, Annette C.; Snoek, Frank J.; Scheltens, Philip; Pouwels, Petra J. W.; Barkhof, Frederik; Diamant, Michaela; Tijms, Betty M.

    2016-01-01

    Type 1 diabetes mellitus (T1DM) patients, especially with concomitant microvascular disease, such as proliferative retinopathy, have an increased risk of cognitive deficits. Local cortical gray matter volume reductions only partially explain these cognitive dysfunctions, possibly because volume

  20. Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

    Science.gov (United States)

    Karri, Venkatanaidu; Schuhmacher, Marta; Kumar, Vikas

    2016-12-01

    Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na + - K + ATP-ase pump (Cd, MeHg), biological Ca +2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice.

    Science.gov (United States)

    Song, Jia; Chu, Shuaishuai; Cui, Yin; Qian, Yue; Li, Xiuxiu; Xu, Fangxia; Shao, Xueming; Ma, Zhengliang; Xia, Tianjiao; Gu, Xiaoping

    2018-04-13

    Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery. Advanced age is a significant independent risk factor for POCD. We previously reported that in young mice, sleep-wake rhythm is involved in the isoflurane-induced memory impairment. In present study, we sought to determine whether advanced age increased the risk of POCD through aggravated and prolonged post-anesthetic circadian disruption in the elderly. We constructed POCD model by submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time (ZT) 14 to ZT19. Under novel object recognition assay (NOR) and Morris water maze (MWM) test, We found 5-h isoflurane anesthesia impaired the cognition of young mice for early 3 days after anesthesia but damaged the aged for at least 1 week. With Mini-Mitter continuously monitoring, a 3.22 ± 0.75 h gross motor activity acrophase delay was manifested in young mice on D1, while in the aged mice, the gross motor activity phase shift lasted for 3 days, consistent with the body temperature rhythm trends of change. Melatonin has been considered as an effective remedy for circadian rhythm shift. In aged mice, melatonin was pretreated intragastrically at the dose of 10 mg/kg daily for 7 consecutive days before anesthesia. We found that melatonin prevented isoflurane-induced cognitive impairments by restoring the locomotor activity and temperature circadian rhythm via clock gene resynchronization. Overall, these results indicated that Long-term isoflurane anesthesia induced more aggravated and prolonged memory deficits and circadian rhythms disruption in aged mice. Melatonin could prevent isoflurane-induced cognitive impairments by circadian rhythm resynchronization. Copyright © 2018. Published by Elsevier Inc.

  2. Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE).

    Science.gov (United States)

    Kozora, E; Erkan, D; West, S G; Filley, C M; Zhang, L; Ramon, G; Duggan, E; Lockshin, M D

    2013-01-01

    Mild cognitive dysfunction (MCD) is common in patients with systemic lupus erythematosus (MCD-SLE) but few studies have investigated potential site differences. SLE patients from Denver, CO, and New York, NY, were enrolled in two different cognition studies employing similar screening methods. Using the resulting neuropsychological scores, cognitive impairment was calculated using a cognitive impairment index (CII). The rate of MCD-SLE was 24% at the Denver, CO, site and 60% at the New York, NY, site. The mean CII was 2.6 ± 2.3 versus 4.4 ± 2.7, respectively (p = 0.005). The NY participants had a significantly longer disease duration (p = 0.13) and higher American College of Rheumatology SLE criteria scores (p > 0.001). NY participants had a higher frequency of impairment in semantic verbal fluency (p = 0.005), visuomotor speed (p = 0.013), and motor sequencing (p = 0.001). A correlation was found between cognitive impairment and SLE disease duration (p = 0.03). The rate of MCD-SLE was greater in SLE patients from New York, NY, compared to patients in the Denver, CO, area. The greater duration of disease and higher prevalence of medical complications in the NY group might contribute to this difference. Findings suggest that MCD-SLE may differ by site, but future studies that better evaluate site or selection bias are recommended.

  3. Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium

    Directory of Open Access Journals (Sweden)

    Brown David M

    2005-10-01

    Full Text Available Abstract Background Particulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter. Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis. Methods In this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively, such as elemental carbon (EC90, commercial carbon (Printex 90, diesel particulate matter (DEP and urban dust (UD, were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320 μg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively. Results Impaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100 μg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.

  4. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    International Nuclear Information System (INIS)

    Lin, Ming-Chung; Chen, Chia-Ling; Yang, Tsan-Tzu; Choi, Pui-Ching; Hsing, Chung-Hsi; Lin, Chiou-Feng

    2012-01-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  5. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ming-Chung [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan (China); Chen, Chia-Ling [Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Yang, Tsan-Tzu; Choi, Pui-Ching [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan (China); Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin@mail.ncku.edu.tw [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China)

    2012-12-01

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

  6. Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors

    Directory of Open Access Journals (Sweden)

    Naoyuki eSato

    2013-11-01

    Full Text Available It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD. Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of 1 compromised vascular reactivity, 2 vascular lesions, 3 hypo/hyperglycemia, and 4 exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. Beta-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: 1 functional MRI or SPECT for cerebrovascular reactivity, 2 MRI for ischemic lesions and atrophy, 3 clinical episodes of hypoglycemia and hyperglycemia, 4 amyloid-PET and tau-PET for pathological features of AD, would be required.

  7. Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

    Science.gov (United States)

    Sato, Naoyuki; Morishita, Ryuichi

    2013-11-05

    It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

  8. Comparison of a gratitude-based and cognitive restructuring intervention for body dissatisfaction and dysfunctional eating behavior in college women.

    Science.gov (United States)

    Wolfe, Wendy L; Patterson, Kaitlyn

    2017-01-01

    Researchers have investigated the efficacy of a gratitude intervention for decreasing body dissatisfaction (BD) in an internet treatment-seeking sample and demonstrated it worked equally well to decrease BD as cognitive restructuring. We extend this research by testing the efficacy of a gratitude intervention on BD, along with common sequelae of BD: dysfunctional eating, negative mood, and depressive symptoms. Females were randomly assigned to Gratitude, Cognitive Restructuring, or Control conditions. Pre- to post-intervention period comparisons found the gratitude intervention to perform better than the other conditions at increasing body esteem, decreasing BD, reducing dysfunctional eating, and reducing depressive symptoms.

  9. Three screening methods for cognitive dysfunction using the Mini-Mental State Examination and Korean Dementia Screening Questionnaire.

    Science.gov (United States)

    Choi, Seong Hye; Park, Moon Ho

    2016-02-01

    To screen for and determine cognitive dysfunction, cognitive tests and/or informant reports are commonly used. However, these cognitive tests and informant reports are not always available. The present study investigated three screening methods using the Mini-Mental State Examination (MMSE) as the cognitive test, and the Korean dementia screening questionnaire (KDSQ) as the informant report. Participants were recruited from the Korea Clinical Research Center for Dementia of South Korea, and included 2861 patients with Alzheimer's disease (dementia), 3519 patients with mild cognitive impairment and 1375 controls with no cognitive dysfunction. Three screening methods were tested: (i) MMSE alone (MMSE(cut-off) ); (ii) a conventional combination of MMSE and KDSQ (MMSE+KDSQ(cut-off) ); and (iii) a decision tree with MMSE and KDSQ (MMSE+KDSQ(decision tree) ). For discriminating any cognitive dysfunction from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.784). For discriminating dementia from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.899). For discriminating mild cognitive impairment from controls, MMSE(cut-off) had the highest area under the receiver operating characteristic curve (0.683). MMSE+KDSQ(decision tree) showed the highest sensitivity for all discriminations. For overall classification accuracy, MMSE+KDSQ(decision tree) had the highest value (70.0%). These three methods had different advantageous properties for screening and staging cognitive dysfunction. As there might be different availability across clinical settings, these three methods can be selected and used according to situational needs. © 2015 Japan Geriatrics Society.

  10. Predictors of outcome in residential cognitive and interpersonal treatment for social phobia: do cognitive and social dysfunction moderate treatment outcome?

    Science.gov (United States)

    Borge, Finn-Magnus; Hoffart, Asle; Sexton, Harold

    2010-09-01

    The predictors of residential cognitive (RCT) and residential interpersonal Treatment (RIPT) for social phobia were explored. (1) Sotsky et al. (1991) found differential effects of CT and IPT for depression, suggesting that the level of cognitive or social dysfunction predicted differential outcome. We examined whether an analogous effect could be demonstrated in 10 weeks of residential treatment of 80 social phobia subjects. (2) We also included expectations, age of onset, severity of illness, concurrent anxiety, mood, avoidant personality disorder, and body dysmorphic disorder as predictors in this exploratory study. Main outcome was the social phobia subscale of Social Phobia and Anxiety Inventory (SPAI SP). DSM-IV axis I and II interviews were completed. (1) Sotsky et al. (1991) findings were not reproduced. However, RIPT subjects with poor general functioning were less improved following treatment. Subjects with concurrent agoraphobia responded better with RCT than subjects without agoraphobia. (2) Age of onset and expectations were the most powerful predictors of post treatment outcome. Some patient characteristics appear to impact outcome with RIPT and RCT differentially. The findings are discussed. (c) 2010 Elsevier Ltd. All rights reserved.

  11. Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice.

    Science.gov (United States)

    Tian, Yue; Guo, Shanbin; Zhang, Yan; Xu, Ying; Zhao, Ping; Zhao, Xiaochun

    2017-05-01

    This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.

  12. Effect of sugammadex versus neostigmine/atropine combination on postoperative cognitive dysfunction after elective surgery.

    Science.gov (United States)

    Batistaki, C; Riga, M; Zafeiropoulou, F; Lyrakos, G; Kostopanagiotou, G; Matsota, P

    2017-09-01

    This study aimed to assess the effects of sugammadex and neostigmine/atropine on postoperative cognitive dysfunction (POCD) in adult patients after elective surgery. A randomised, double-blind controlled trial was carried out on 160 American Society of Anesthesiologists physical status I to III patients who were >40 years. The Mini-Mental State Evaluation, clock-drawing test and the Isaacs Set test were used to assess cognitive function at three timepoints: 1) preoperatively, 2) one hour postoperatively, and 3) at discharge. The anaesthetic protocol was the same for all patients, except for the neuromuscular block reversal, which was administered by random allocation using either sugammadex or neostigmine/atropine after the reappearance of T2 in the train-of-four sequence. POCD was defined as a decline ≥1 standard deviation in ≥2 cognitive tests. The incidence of POCD was similar in both groups at one hour postoperatively and at discharge (28% and 10%, in the neostigmine group, 23% and 5.4% in the sugammadex group, P =0.55 and 0.27 respectively). In relation to individual tests, a significant decline of clock-drawing test in the neostigmine group was observed at one hour postoperatively and at discharge. For the Isaacs Set test, a greater decline was found in the sugammadex group. These findings suggest that there are no clinically important differences in the incidence of POCD after neostigmine or sugammadex administration.

  13. Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence.

    Science.gov (United States)

    Ersche, Karen D; Turton, Abigail J; Chamberlain, Samuel R; Müller, Ulrich; Bullmore, Edward T; Robbins, Trevor W

    2012-09-01

    Not everyone who takes drugs becomes addicted, but the likelihood of developing drug addiction is greater in people with a family history of drug or alcohol dependence. Relatively little is known about how genetic risk mediates the development of drug dependence. By comparing the phenotypic profile of individuals with and without a family history of addiction, the authors sought to clarify the extent to which cognitive dysfunction and personality traits are shared by family members--and therefore likely to have predated drug dependence--and which aspects are specific to drug-dependent individuals. The authors assessed cognitive function and personality traits associated with drug dependence in stimulant-dependent individuals (N=50), their biological siblings without a history of drug dependence (N=50), and unrelated healthy volunteers (N=50). Cognitive function was significantly impaired in the stimulant-dependent individuals across a range of domains. Deficits in executive function and response control were identified in both the stimulant-dependent individuals and in their non-drug-dependent siblings. Drug-dependent individuals and their siblings also exhibited elevated anxious-impulsive personality traits relative to healthy comparison volunteers. Deficits in executive function and response regulation as well as anxious-impulsive personality traits may represent endophenotypes associated with the risk of developing cocaine or amphetamine dependence. The identification of addiction endophenotypes may be useful in facilitating the rational development of therapeutic and preventive strategies.

  14. The role of nonverbal cognitive ability in the association of adverse life events with dysfunctional attitudes and hopelessness in adolescence.

    Science.gov (United States)

    Flouri, Eirini; Panourgia, Constantina

    2012-10-01

    The aim of this study was to test whether nonverbal cognitive ability buffers the effect of life stress (number of adverse life events in the last year) on diatheses for depression. It was expected that, as problem-solving aptitude, nonverbal cognitive ability would moderate the effect of life stress on those diatheses (such as dysfunctional attitudes) that are depressogenic because they represent deficits in information-processing or problem-solving skills, but not on diatheses (such as hopelessness) that are depressogenic because they represent deficits in motivation or effort to apply problem-solving skills. The sample included 558 10- to 19-year-olds from a state secondary school in London. Nonverbal cognitive ability was negatively associated with both dysfunctional attitudes and hopelessness. As expected, nonverbal cognitive ability moderated the association between life adversity and dysfunctional attitudes. However, hopelessness was not related to life stress, and therefore, there was no life stress effect for nonverbal cognitive ability to moderate. This study adds to knowledge about the association between problem-solving ability and depressogenic diatheses. By identifying life stress as a risk factor for dysfunctional attitudes but not hopelessness, it highlights the importance of considering outcome specificity in models predicting adolescent outcomes from adverse life events. Importantly for practice, it suggests that an emphasis on recent life adversity will likely underestimate the true level of hopelessness among adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  16. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

    Science.gov (United States)

    Manna, Prasenjit

    2015-01-01

    Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue

  17. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

    Science.gov (United States)

    Manna, Prasenjit; Jain, Sushil K

    2015-12-01

    Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in

  18. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  19. Occlusion and brain function: mastication as a prevention of cognitive dysfunction.

    Science.gov (United States)

    Ono, Y; Yamamoto, T; Kubo, K-ya; Onozuka, M

    2010-08-01

    Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress-attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic-pituitary-adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication-induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.

  20. A comparison of 2 screening questionnaires for clinical assessment of canine cognitive dysfunction

    DEFF Research Database (Denmark)

    Schütt, Trine; Toft, Nils; Berendt, Mette

    2015-01-01

    Canine cognitive dysfunction (CCD) is a neurobehavioral syndrome occurring in some senior dogs. The diagnosis is currently primarily dependent on owner-based questionnaires addressing changes in behavior and daily routines and the exclusion of other conditions which may display clinical signs...... mimicking CCD. A number of CCD screening questionnaires have been published, but whether the choice of questionnaire might influence the diagnosis of CCD or not, is unclear. The objective of the present study was to correlate the total scores from 2 CCD screening questionnaires which were developed...... on the basis of very different strategies. The study population consisted of 50 dogs more than 8years of age. The dogs were evaluated clinically, and the 2 questionnaires were given in a face-to-face interview with the owners. The study found a significant correlation (r= 0.83, P

  1. Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

    Directory of Open Access Journals (Sweden)

    Egidio eD‘Angelo

    2013-01-01

    Full Text Available Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive and emotional functions (at least partially segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis: from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the timing and learning machine capabilities long attributed to the cerebellum, which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia and depression.

  2. SPM analysis and cognitive dysfunctions in patients with transient global amnesia

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Kang, Do Young; Yun, Go Un; Park, Kyung Won; Kim, Jae Woo

    2004-01-01

    Transient global amnesia (TGA) is known as a disease of benign nature characterized with clinically transient global antegrade amnesia and a variable degree of global retrograde memory impairment, but it usually resolved within 24 hours. The aims of this study are to assess the alterations in regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT imaging with statistical parametric mapping (SPM) analysis and to verify the cognitive deficits by neuropsychological test in TGA patients. Twelve patients with TGA and age-matched normal control subjects participated in this study. Tc-99m HMPAO SPECT was performed within 1 to 19 days (mean duration: 7.3:±5.2 days) after the events to measure the rCBF. SPECT images were analyzed using SPM (SPM99) with Matlab 5.3. Seoul Neuropsychological Screening Battery test was also done within 2 to 8 days (mean duration 3.8±2.2 days) for cognitive functions in 8 of 12 patients with TGA. The SPM analysis of SPECT images showed significantly decreased rCBF in the left inferior frontal gyrus (Brodmann area 9), the left supramarginal gyrus (Brodmann area 40), the left postcentral gyrus (Brodmann area 40) and the left precentral gyrus (Brodmann area 4) in patients with TGA (uncorrected p<0.01). Neuropsychological test findings represented that several cognitive functions. such as, verbal memory, visual memory, phonemic fluency and confrontational naming, were impaired in patients with TGA compared with normal control. Additionally, on SPM analysis, we found lesions of hyperperfusion in contralateral cerebral hemisphere. Our study shows perfusion deficits in the left cerebral hemisphere in patients with TGA and several cognitive dysfunctions. And we found after clinical symptoms were completely resolved, the lesions of hypoperfusion were still remained. We found that functional quantitative neuroimaging study and neuropsychological test are useful to understand underlying pathomachanism of TGA

  3. SPM analysis and cognitive dysfunctions in patients with transient global amnesia

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Yun, Go Un; Park, Kyung Won; Kim, Jae Woo [School of Medicine, Donga University, Busan (Korea, Republic of)

    2004-07-01

    Transient global amnesia (TGA) is known as a disease of benign nature characterized with clinically transient global antegrade amnesia and a variable degree of global retrograde memory impairment, but it usually resolved within 24 hours. The aims of this study are to assess the alterations in regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT imaging with statistical parametric mapping (SPM) analysis and to verify the cognitive deficits by neuropsychological test in TGA patients. Twelve patients with TGA and age-matched normal control subjects participated in this study. Tc-99m HMPAO SPECT was performed within 1 to 19 days (mean duration: 7.3:{+-}5.2 days) after the events to measure the rCBF. SPECT images were analyzed using SPM (SPM99) with Matlab 5.3. Seoul Neuropsychological Screening Battery test was also done within 2 to 8 days (mean duration 3.8{+-}2.2 days) for cognitive functions in 8 of 12 patients with TGA. The SPM analysis of SPECT images showed significantly decreased rCBF in the left inferior frontal gyrus (Brodmann area 9), the left supramarginal gyrus (Brodmann area 40), the left postcentral gyrus (Brodmann area 40) and the left precentral gyrus (Brodmann area 4) in patients with TGA (uncorrected p<0.01). Neuropsychological test findings represented that several cognitive functions. such as, verbal memory, visual memory, phonemic fluency and confrontational naming, were impaired in patients with TGA compared with normal control. Additionally, on SPM analysis, we found lesions of hyperperfusion in contralateral cerebral hemisphere. Our study shows perfusion deficits in the left cerebral hemisphere in patients with TGA and several cognitive dysfunctions. And we found after clinical symptoms were completely resolved, the lesions of hypoperfusion were still remained. We found that functional quantitative neuroimaging study and neuropsychological test are useful to understand underlying pathomachanism of TGA.

  4. Dysfunctional beliefs in group and individual cognitive behavioral therapy for obsessive compulsive disorder.

    Science.gov (United States)

    Jónsson, Hjalti; Hougaard, Esben; Bennedsen, Birgit E

    2011-05-01

    The primary aim of the study was to investigate dysfunctional beliefs in the form of inflated responsibility (IR) and thought action fusion (TAF) as predictive and mediating variables in individual (n=33) and group (n=37) cognitive behavioral therapy (CBT) for obsessive compulsive disorder (OCD). IR and TAF declined significantly during CBT, and the decline was positively associated with change in OCD symptoms. However, when controlling for change in depressive symptoms, only change in IR remained significantly associated with OCD symptom change. The moral subtype of TAF predicted poorer treatment outcome, but only in group CBT. Both treatments produced a similar amount of change in the dysfunctional beliefs. The results provide some, preliminary evidence that IR, but not TAF, may be specifically involved in the change mechanisms of both individual and group CBT for OCD, although the design of the study with pre- and post-therapy measurements only does not allow for a causal mediator analysis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Incidental white-matter foci on MRI in ''healthy'' subjects: evidence of subtle cognitive dysfunction

    International Nuclear Information System (INIS)

    Baum, K.A.; Schulte, C.; Girke, W.; Reischies, F.M.; Felix, R.

    1996-01-01

    The clinical significance of incidental white-matter foci seen on MRI is controversial. Mainly using a computer-assisted neuropsychological test battery, we tested the hypothesis that there is a clinical correlate of these foci. We studied 41 individuals aged 45-65 years with no history of neurological or psychiatric disorder, in whom no indication of central nervous system abnormalities was found on standardised neurological examination. A computer-assisted neuropsychological test battery, with the advantage of precise measuring of both time and deviation (e. g. in position memory tests), and rating scales for emotional dysfunction were administered; selected soft neurological signs were assessed. In 16 subjects (39 %) MRI showed high-signal foci in the white matter on spin-echo sequences. White-matter foci not adjacent to the lateral ventricles were found to be related to performance on immediate visual memory/visuoperceptual skills, visuomotor tracking/psychomotor speed and, to a lesser degree, learning capacity and abstract and conceptual reasoning skills. Subtle cognitive dysfunction would appear to be a clinical correlate of punctate white-matter foci on MRI of otherwise ''healty'' individuals. (orig.). With 1 fig., 2 tabs

  6. Radiation-induced cognitive dysfunction: an experimental model in the old rat

    Energy Technology Data Exchange (ETDEWEB)

    Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

    1995-01-01

    Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p {<=} 0.001) and two-way avoidance (18% vs. 40%, p {<=} 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p {<=} 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

  7. Radiation-induced cognitive dysfunction: an experimental model in the old rat

    International Nuclear Information System (INIS)

    Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

    1995-01-01

    Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes

  8. Radiation-induced cognitive dysfunction: An experimental model in the old rat

    International Nuclear Information System (INIS)

    Lamproglou, I.; Chen, Q.M.; Poisson, M.

    1995-01-01

    To develop a model of radiation-induced behavioral dysfunction. A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes. 15 refs., 3 figs., 1 tab

  9. Effect of chronic forced swimming stress on whole brain radiation induced cognitive dysfunction and related mechanism

    International Nuclear Information System (INIS)

    Zhang Yuan; Sun Rui; Zhu Yaqun; Zhang Liyuan; Ji Jianfeng; Li Kun; Tian Ye

    2014-01-01

    Objective: To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods: Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group(C), swimming group(C-S), radiation group(R), and radiation plus swimming group(R-S). Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results: On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P 0.05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation (P < 0.05), but this reduction was attenuated by the chronic forced swimming stress. Conclusion: The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus. (authors)

  10. Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

    Science.gov (United States)

    Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

    2012-10-01

    Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Magnitude of cognitive dysfunction in adults with type 2 diabetes: a meta-analysis of six cognitive domains and the most frequently reported neuropsychological tests within domains

    NARCIS (Netherlands)

    Palta, P.; Schneider, A.; Biessels, G.J.; Touradji, P.; Hill-Briggs, F.

    2014-01-01

    The objectives were to conduct a meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards to determine effect sizes (Cohen’s d) for cognitive dysfunction in adults with type 2 diabetes, relative to nondiabetic controls, and to obtain

  12. Association between unsafe driving performance and cognitive-perceptual dysfunction in older drivers.

    Science.gov (United States)

    Park, Si-Woon; Choi, Eun Seok; Lim, Mun Hee; Kim, Eun Joo; Hwang, Sung Il; Choi, Kyung-In; Yoo, Hyun-Chul; Lee, Kuem Ju; Jung, Hi-Eun

    2011-03-01

    prevalent in older drivers than in younger drivers. Unsafe performance in steering, vehicle positioning, making lane changes, and car crashes were associated with cognitive-perceptual dysfunction. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery

    NARCIS (Netherlands)

    Kok, W F; Koerts, Janneke; Tucha, O; Scheeren, T W L; Absalom, A R

    Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein β, as well as plasma-free

  14. Are all models susceptible to dysfunctional cognitions about eating and body image? The moderating role of personality styles.

    Science.gov (United States)

    Blasczyk-Schiep, Sybilla; Sokoła, Kaja; Fila-Witecka, Karolina; Kazén, Miguel

    2016-06-01

    We investigated dysfunctional cognitions about eating and body image in relation to personality styles in a group of professional models. Dysfunctional cognitions in professional models (n = 43) and a control group (n = 43) were assessed with the 'Eating Disorder Cognition Questionnaire' (EDCQ), eating attitudes with the 'Eating Attitudes Test' (EAT), and personality with the 'Personality Styles and Disorders Inventory' (PSDI-S). Models had higher scores than controls on the EDCQ and EAT and on nine scales of the PSDI-S. Moderation analyses showed significant interactions between groups and personality styles in predicting EDCQ scales: The ambitious/narcissistic style was related to "negative body and self-esteem", the conscientious/compulsive style to "dietary restraint", and the spontaneous/borderline style to "loss of control in eating". The results indicate that not all models are susceptible to dysfunctional cognitions about eating and body image. Models are at a higher risk of developing negative automatic thoughts and dysfunctional assumptions relating to body size, shape and weight, especially if they have high scores on the above personality styles.

  15. Oxidized CaMKII causes cardiac sinus node dysfunction in mice

    Science.gov (United States)

    Swaminathan, Paari Dominic; Purohit, Anil; Soni, Siddarth; Voigt, Niels; Singh, Madhu V.; Glukhov, Alexey V.; Gao, Zhan; He, B. Julie; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Kutschke, William; Yang, Jinying; Donahue, J. Kevin; Weiss, Robert M.; Grumbach, Isabella M.; Ogawa, Masahiro; Chen, Peng-Sheng; Efimov, Igor; Dobrev, Dobromir; Mohler, Peter J.; Hund, Thomas J.; Anderson, Mark E.

    2011-01-01

    Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47–/– mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII–triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients. PMID:21785215

  16. Serratus muscle stimulation effectively treats notalgia paresthetica caused by long thoracic nerve dysfunction: a case series

    Directory of Open Access Journals (Sweden)

    Barad Meredith

    2009-09-01

    Full Text Available Abstract Currently, notalgia paresthetica (NP is a poorly-understood condition diagnosed on the basis of pruritus, pain, or both, in the area medial to the scapula and lateral to the thoracic spine. It has been proposed that NP is caused by degenerative changes to the T2-T6 vertebrae, genetic disposition, or nerve entrapment of the posterior rami of spinal nerves arising at T2-T6. Despite considerable research, the etiology of NP remains unclear, and a multitude of different treatment modalities have correspondingly met with varying degrees of success. Here we demonstrate that NP can be caused by long thoracic nerve injury leading to serratus anterior dysfunction, and that electrical muscle stimulation (EMS of the serratus anterior can successfully and conservatively treat NP. In four cases of NP with known injury to the long thoracic nerve we performed transcutaneous EMS to the serratus anterior in an area far lateral to the site of pain and pruritus, resulting in significant and rapid pain relief. These findings are the first to identify long thoracic nerve injury as a cause for notalgia paresthetica and electrical muscle stimulation of the serratus anterior as a possible treatment, and we discuss the implications of these findings on better diagnosing and treating notalgia paresthetica.

  17. Basal ganglia calcification as a putative cause for cognitive decline

    Directory of Open Access Journals (Sweden)

    João Ricardo Mendes de Oliveira

    Full Text Available ABSTRACT Basal ganglia calcifications (BGC may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients

  18. Basal ganglia calcification as a putative cause for cognitive decline.

    Science.gov (United States)

    de Oliveira, João Ricardo Mendes; de Oliveira, Matheus Fernandes

    2013-01-01

    Basal ganglia calcifications (BGC) may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients.

  19. TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND FIBRIN MONOMERS SYNERGISTICALLY CAUSE PLATELET DYSFUNCTION DURING RETRANSFUSION OF SHED BLOOD AFTER CARDIOPULMONARY BYPASS

    NARCIS (Netherlands)

    DEHAAN, J; SCHONBERGER, J; HAAN, J; VANOEVEREN, W; EIJGELAAR, A

    1993-01-01

    Reduced hemostasis and bleeding tendency after cardiopulmonary bypass results from platelet dysfunction induced by the bypass procedure. The causes of this acquired platelet dysfunction are still subject to discussion, although, recently, greater emphasis has been placed on an overstimulated

  20. Effects of galangal extract on cognitive dysfunction and nerve pathological change in rats with diabetic encephalopathy

    Directory of Open Access Journals (Sweden)

    Dao-Rui Yu

    2016-09-01

    Full Text Available Objective: To evaluate the effects of galangal extract on cognitive dysfunction and nerve pathological change in rats with diabetic encephalopathy. Methods: Sixty male SD rats were given high sugar and fat diet except the control group. Fifty days later, the animals were injected with STZ 30 mg/kg through intraperitoneal to establish type 2 diabetes model. Rats were divided into control group, model group, Metformin group, oxiracetam group, galangal extract high and low dose group. After 4-week administration, Morris water maze was utilized to investigate the effects of different galangal extract on learning and memory ability in rats. After behavioral testing, the blood sugar level was detected. Meanwhile, spectrophotometer was used to measure the superoxide dismutase (SOD activity and maleic dialdehyde (MDA content of brain tissue. HE staining was used to observe the morphological changes in the hippocampus. Results: Galangal extract can significantly reduce swimming time and swimming distance of diabetic encephalopathy rat model, lower fasting blood glucose while increase body weight. At the same time, SOD activity and MDA content of rat brain were reduced. The morphology of neurons in hippocampus was improved and neuronal nuclear condensation was reduced correspondingly. Conclusions: Galangal extract can significantly improve cognitive ability in diabetic rats, reduce hippocampal pathological changes and have some prevention or treatment effects on of diabetes encephalopathy

  1. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    International Nuclear Information System (INIS)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio

    2001-01-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

  2. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

    Science.gov (United States)

    Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

    2015-01-01

    Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

  3. Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    El Batsh, Maha M; El Batch, Manal M; Shafik, Noha M; Younos, Ibrahim H

    2015-12-15

    Progression of diabetes mellitus is accompanied by metabolic disorders together with psychological deficits including cognitive dysfunctions. Herein, we used a murine streptozotocin (STZ)-induced diabetes to investigate the beneficial effects of vildagliptin not only on metabolic abnormalities, but also on diabetes-induced cognitive decline. Sixty rats were divided randomly and equally into 2 groups; one remains normal and the other serves as STZ- induced diabetic. Both groups were further divided equally into 2 groups; one received vehicle and the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed using novel object recognition test. Blood samples were collected to measure metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were removed and investigated for the levels of inflammatory and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-κB)/p65. Treatment of STZ-induced diabetic rats with vildagliptin increased their body weight and corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin significantly decreased serum levels of glucose and lipids (except high density lipoprotein) together with brain MDA, TNF-α, serum DPP-IV activities and NF-κB/p65 gene expression. On the other hand, vildagliptin significantly increased brain BDNF, SOD as well as serum insulin. Results suggested that vildagliptin has a protective role in counteracting both metabolic abnormalities and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, anti-inflammatory, antioxidant effects, together with reduction of brain NF-κB/p65 over expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

    Science.gov (United States)

    Song, Juhyun; Hur, Bo Eun; Bokara, Kiran Kumar; Yang, Wonsuk; Cho, Hyun Jin; Park, Kyung Ah; Lee, Won Taek; Lee, Kyoung Min

    2014-01-01

    Purpose Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. Materials and Methods We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 µL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. Results Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and γ-glutamyl cysteine synthetase, in the STZ-Agm group. Conclusion Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD. PMID:24719136

  5. [Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

    Science.gov (United States)

    Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

    2014-01-01

    Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

  6. Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study

    OpenAIRE

    Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

    2016-01-01

    Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on sta...

  7. [Diagnosis of temporo-mandibular joint dysfunction caused by occlusion pathology and treatment of such patients].

    Science.gov (United States)

    Semkin, V A; Rabukhina, N A; Kravchenko, D V

    2007-01-01

    Patients with temporo-mandibular joint (TMJ) dysfunction need complex treatment that includes prosthetic treatment in intrajoint relation stabilization. In cases of TMJ pathology it is necessary to examine patients and make axiography, function analysis, MPI-analysis, magnetic resonance tomography and zonography of TMJ, electromyography of the masticatory muscles. The authors examined 47 patients with TMJ dysfunction, 43 of them had occlusion pathology. We managed to eliminate the dysfunction symptoms and to receive stable result of the treatment in all the patients.

  8. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    International Nuclear Information System (INIS)

    Sobinoff, A.P.; Beckett, E.L.; Jarnicki, A.G.; Sutherland, J.M.; McCluskey, A.; Hansbro, P.M.; McLaughlin, E.A.

    2013-01-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  9. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sobinoff, A.P. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); Beckett, E.L.; Jarnicki, A.G. [Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308 (Australia); Sutherland, J.M. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); McCluskey, A. [Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); Hansbro, P.M. [Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia)

    2013-09-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  10. Effects of Short-Term Cognitive Remediation on Cognitive Dysfunction in Partially or Fully Remitted Individuals with Bipolar Disorder: Results of a Randomised Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Kirsa M Demant

    Full Text Available Cognitive dysfunction is common in bipolar disorder (BD but is not sufficiently addressed by current treatments. Cognitive remediation (CR may improve cognitive function in schizophrenia but no randomised controlled trial has investigated this intervention in BD. The present study aimed to investigate the effects of CR on persistent cognitive dysfunction in BD.Patients with BD in partial remission with cognitive complaints were randomised to 12 weeks group-based CR (n=23 or standard treatment (ST (n=23. Outcomes were improved verbal memory (primary, sustained attention, executive and psychosocial function (secondary and additional measures of cognitive and psychosocial function (tertiary. Participants were assessed at baseline and weeks 12 and 26.Of the 46 randomised participants five dropped out and one was excluded after baseline. CR (n=18 had no effect on primary or secondary measures of cognitive or psychosocial function compared with ST (n=22. However, CR improved subjective sharpness at week 12, and quality of life and verbal fluency at week 26 follow-up (tertiary outcomes. Although the trial turned out to have suboptimal statistical power for the primary outcome analysis, calculation of the 95% confidence interval showed that it was highly unlikely that an increase in sample size would have rendered any beneficial effects of CR vs. ST on the verbal memory.Short-term group-based CR did not seem to improve overall cognitive or psychosocial function in individuals with BD in full or partial remission. The present findings suggest that that longer-term, more intensive and individualised CR may be necessary to improve cognition in BD.ClinicalTrials.gov NCT01457235.

  11. Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

    Science.gov (United States)

    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2010-02-01

    Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

  12. A vanillin derivative causes mitochondrial dysfunction and triggers oxidative stress in Cryptococcus neoformans.

    Science.gov (United States)

    Kim, Jin Hyo; Lee, Han-Ok; Cho, Yong-Joon; Kim, Jeongmi; Chun, Jongsik; Choi, Jaehyuk; Lee, Younghoon; Jung, Won Hee

    2014-01-01

    Vanillin is a well-known food and cosmetic additive and has antioxidant and antimutagenic properties. It has also been suggested to have antifungal activity against major human pathogenic fungi, although it is not very effective. In this study, the antifungal activities of vanillin and 33 vanillin derivatives against the human fungal pathogen Cryptococcus neoformans, the main pathogen of cryptococcal meningitis in immunocompromised patients, were investigated. We found a structural correlation between the vanillin derivatives and antifungal activity, showing that the hydroxyl or alkoxy group is more advantageous than the halogenated or nitrated group in benzaldehyde. Among the vanillin derivatives with a hydroxyl or alkoxy group, o-vanillin and o-ethyl vanillin showed the highest antifungal activity against C. neoformans. o-Vanillin was further studied to understand the mechanism of antifungal action. We compared the transcriptome of C. neoformans cells untreated or treated with o-vanillin by using RNA sequencing and found that the compound caused mitochondrial dysfunction and triggered oxidative stress. These antifungal mechanisms of o-vanillin were experimentally confirmed by the significantly reduced growth of the mutants lacking the genes involved in mitochondrial functions and oxidative stress response.

  13. Pemphigus—A Disease of Desmosome Dysfunction Caused by Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Volker Spindler

    2018-02-01

    Full Text Available Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components. These pathways include Ca2+, p38MAPK, PKC, Src, EGFR/Erk, and several others. In this review, we delineate the mechanisms relevant for pemphigus pathogenesis based on the histology and the ultrastructure of patients’ lesions. We then dissect the mechanisms which can explain the ultrastructural hallmarks detectable in pemphigus patient skin. Finally, we reevaluate the concept that the spectrum of mechanisms, which induce desmosome dysfunction upon binding of pemphigus autoantibodies, finally defines the clinical phenotype.

  14. Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Shen, Qingyu; Lin, Focai; Rong, Xiaoming; Yang, Wuyang; Li, Yi; Cai, Zhaoxi; Xu, Pengfei; Xu, Yongteng; Tang, Yamei

    2016-01-01

    Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitive function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN

  15. Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Qingyu [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Department of Neurology, Zengcheng People' s Hospital, Guangzhou (China); Lin, Focai; Rong, Xiaoming [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Yang, Wuyang [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Li, Yi; Cai, Zhaoxi; Xu, Pengfei; Xu, Yongteng [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Tang, Yamei, E-mail: yameitang@hotmail.com [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou (China); Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province (China)

    2016-04-01

    Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitive function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN

  16. Executive Dysfunction

    Science.gov (United States)

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  17. Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

    Science.gov (United States)

    Hai, Lan; Hiremath, Deepak S; Paquet, Marilène; Narayan, Prema

    2017-05-01

    The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

  18. Effects of adenosine on the organ injury and dysfunction caused by hemorrhagic shock

    International Nuclear Information System (INIS)

    Soliman, M.M.

    2009-01-01

    Objectives: Adenosine has been shown in animal and human studies to decrease the post-ischemic myocardial injury by lowering the levels of tumor necrosis factor-a. The objectives of the study was to examine the protective effects of adenosine on the organ injury (liver, kidney, pancreas) associated with hemorrhagic shock in rats. Methodology: The study was conducted at Cardiovascular Physiology laboratory, King Saud University, Riyadh in 2007-2008. Anesthetized male Sprague- Dawley rats were assigned to hemorrhage and resuscitation treated with 20mM adenosine , untreated, or similar time matched control groups (n=6 per group). Rats were hemorrhaged for one hour using a reservoir model. Arterial blood pressure was monitored for one hour, and maintained at a mean arterial blood pressure of 40 mmHg. Adenosine 20mM was injected intra-arterially, before resuscitation in the adenosine treated group. Resuscitation was performed by re infusion of the sheded blood for 30 minutes. Arterial blood samples were analyzed for biochemical indicators of multiple organ injury: 1) liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), 2) renal function: urea and creatinine, 3) pancreatic function: amylase. Results: In the control group there was no significant rise in the serum levels of (i) urea and creatinine, (ii) aspartate aminotransferase (AST) and alanine aminotransferase (ALT), (iii) amylase. While in the adenosine treated group, resuscitation from one hour of hemorrhagic shock resulted in significant rises in the serum levels of (i) urea and creatinine, (ii) aspartate aminotransferase (AST) and alanine aminotransferase (ALT), (iii) amylase. Treatment of rats with 20mM adenosine before resuscitation following one hour of hemorrhagic shock decreased the multiple organ injury and dysfunction caused by hemorrhagic shock. Conclusion: Adenosine attenuated the renal, liver and pancreatic injury caused by hemorrhagic shock and resuscitation in rats. Thus

  19. Cognitive dysfunctions in occipital lobe epilepsy compared to temporal lobe epilepsy.

    Science.gov (United States)

    Santangelo, Gabriella; Trojano, Luigi; Vitale, Carmine; Improta, Ilaria; Alineri, Irma; Meo, Roberta; Bilo, Leonilda

    2017-06-01

    To compare cognitive profiles of occipital lobe epilepsy (OLE) and temporal lobe epilepsy (TLE) and to investigate whether impairment of visuospatial functions is a specific deficit of OLE. Eighteen patients with OLE, 18 patients with TLE, and 18 controls underwent a neuropsychological battery assessing memory, visuospatial functions, and frontal/executive functions. Multivariate analysis evidenced poorer performance of patients with TLE and patients with OLE relative to controls on tasks assessing verbal and non-verbal long-term memory, frontal functions, and visuospatial functions. Patients with OLE had poorer performance than patients with TLE on visuospatial tasks, whereas patients with TLE performed worse than patients with OLE on verbal long-term memory test. Discriminant analysis identified two canonical discriminant functions: The first explained 53.3% of the variance, and the second explained 46.7% of the variance. The first function included verbal and non-verbal memory tests distinguishing controls from both OLE and TLE, whereas the second factor including a visuoconstructional test distinguished OLE from TLE and controls. The results demonstrate that visuoconstructional dysfunction is related to OLE and support the idea that alterations of occipito-parietal stream may be specific to patients with OLE. © 2015 The British Psychological Society.

  20. Cognitive Dysfunction after On-Pump Operations: Neuropsychological Characteristics and Optimal Core Battery of Tests

    Directory of Open Access Journals (Sweden)

    Anna G. Polunina

    2014-01-01

    Full Text Available Postoperative cognitive dysfunction (POCD is a mild form of perioperative ischemic brain injury, which emerges as memory decline, decreased attention, and decreased concentration during several months, or even years, after surgery. Here we present results of our three neuropsychological studies, which overall included 145 patients after on-pump operations. We found that the auditory memory span test (digit span was more effective as a tool for registration of POCD, in comparison with the word-list learning and story-learning tests. Nonverbal memory or visuoconstruction tests were sensitive to POCD in patients after intraoperative opening of cardiac chambers with increased cerebral air embolism. Psychomotor speed tests (digit symbol, or TMT A registered POCD, which was characteristic for elderly atherosclerotic patients. Finally, we observed that there were significant effects of the order of position of a test on the performance on this test. For example, the postoperative performance on the core tests (digit span and digit symbol showed minimal impairment when either of these tests was administered at the beginning of testing. Overall, our data shows that the selection of tests, and the order of which these tests are administered, may considerably influence the results of studies of POCD.

  1. Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

    Science.gov (United States)

    Rimoldi, Stefano F; Rexhaj, Emrush; Duplain, Hervé; Urben, Sébastien; Billieux, Joël; Allemann, Yves; Romero, Catherine; Ayaviri, Alejandro; Salinas, Carlos; Villena, Mercedes; Scherrer, Urs; Sartori, Claudio

    2016-02-01

    To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Donepezil for treatment of cognitive dysfunction in children with Down syndrome aged 10-17.

    Science.gov (United States)

    Kishnani, Priya S; Heller, James H; Spiridigliozzi, Gail A; Lott, Ira; Escobar, Luis; Richardson, Sharon; Zhang, Richard; McRae, Thomas

    2010-12-01

    The objective of this 10-week, randomized, double-blind, placebo-controlled multicenter study was to assess the efficacy and safety of donepezil for the treatment of cognitive dysfunction exhibited by children with Down syndrome (DS). Intervention comprised donepezil (2.5-10 mg/day) in children (aged 10-17 years) with DS of mild-to-moderate severity. The primary measures were the Vineland-II Adaptive Behavior Scales (VABS-II) Parent/Caregiver Rating Form (PCRF) the sum of nine subdomain standardized scores and standard safety measures. Secondary measures included the VABS-II/PCRF scores on the following domains and their respective individual subdomains: Communication (receptive, expressive, and written); Daily Living Skills (personal, domestic, and community); Socialization (interpersonal relationships, play and leisure time, and coping skills), and scores on the Test of Verbal Expression and Reasoning, a subject-performance-based measure of expressive language. At baseline, 129 participants were assigned treatment with donepezil or placebo. During the double-blind phase, VABS II/PCRF sum of the nine subdomain standardized scores, called v-scores, improved significantly from baseline in both groups (P < 0.0001), with no significant between-group differences. This trial failed to demonstrate any benefit for donepezil versus placebo in children and adolescents with DS, although donepezil appeared to be well tolerated. © 2010 Wiley-Liss, Inc.

  3. [Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

    Science.gov (United States)

    Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

    2014-01-01

    The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

  4. The effect of two different glycemic management protocols on postoperative cognitive dysfunction in coronary artery bypass surgery

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    Pinar Kurnaz

    Full Text Available Abstract Introduction: Postoperative cognitive dysfunction (POCD is an adverse outcome of surgery that is more common after open heart procedures. The aim of this study is to investigate the role of tightly controlled blood glucose levels during coronary artery surgery on early and late cognitive decline. Methods: 40 patients older than 50 years undergoing elective coronary surgery were randomized into two groups. In the "Tight Control" group (GI, the glycemia was maintained between 80 and 120 mg dL-1 while in the "Liberal" group (GII, it ranged between 80-180 mg dL-1. A neuropsychological test battery was performed three times: baseline before surgery and follow-up first and 12th weeks, postoperatively. POCD was defined as a drop of one standard deviation from baseline on two or more tests. Results: At the postoperative first week, neurocognitive tests showed that 10 patients in the GI and 11 patients in GII had POCD. The incidence of early POCD was similar between groups. However the late assessment revealed that cognitive dysfunction persisted in five patients in the GII whereas none was rated as cognitively impaired in GI (p = 0.047. Conclusion: We suggest that tight perioperative glycemic control in coronary surgery may play a role in preventing persistent cognitive impairment.

  5. Improvement of postoperative cognitive dysfunction and attention network function of patients with ischemic cerebrovascular disease via dexmedetomidine.

    Science.gov (United States)

    Zhang, Jingchao; Wang, Guoliang; Zhang, Fangxiang; Zhao, Qian

    2018-03-01

    The protective effect of dexmedetomidine on cognitive dysfunction and decreased attention network function of patients with ischemic cerebrovascular disease after stenting was investigated. Fifty-eight patients with ischemic cerebrovascular disease undergoing stenting in Guizhou Provincial People's Hospital were selected and randomly divided into control group (n=29) and dexmedetomidine group (n=29). The dexmedetomidine group was treated with dexmedetomidine before induced anesthesia, while the control group was given the same dose of normal saline; and the normal volunteers of the same age were selected as the normal group (n=29). At 3 days after operation, the levels of serum S100B and nerve growth factor (NGF) in each group were detected using the enzyme-linked immunosorbent assay, and the level of brain-derived neurotrophic factor (BDNF) was detected via western blotting. Montreal cognitive assessment (MoCA) and attention network test (ANT) were performed. Moreover, the cognitive function and attention network function, and the effects of dexmedetomidine on cognitive function and attention network function were evaluated. The concentrations of serum S100B and NGF in dexmedetomidine group was lower than those in control group (Pfunction scores, attention scores, delayed memory scores, targeted network efficiency and executive control network efficiency in dexmedetomidine group were obviously higher than those in control group (Pcognitive function and attention network function of patients with ischemic cerebrovascular disease have a certain degree of damage, and the preoperative administration of dexmedetomidine can effectively improve the patient's cognitive dysfunction and attention network function after operation.

  6. Long-term anorectal, urinary and sexual dysfunction causing distress after radiotherapy for anal cancer

    DEFF Research Database (Denmark)

    Sunesen, K G; Nørgaard, M; Lundby, L

    2015-01-01

    . For each symptom we assessed frequency and severity and the level of symptom-induced distress (no, little, moderate or great distress). RESULTS: Of 94 eligible patients, 84 (89%) returned the completed questionnaire at a median of 33 months after radiotherapy. Incontinence for solid stools, liquid stools...... function. CONCLUSION: Distressing long-term anorectal and sexual dysfunction was common after radiotherapy for anal cancer, and morbidity due to urinary dysfunction was moderate....

  7. The Brewed Rice Vinegar Kurozu Increases HSPA1A Expression and Ameliorates Cognitive Dysfunction in Aged P8 Mice.

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    Hiroaki Kanouchi

    Full Text Available Kurozu is a traditional Japanese rice vinegar. During fermentation and aging of the Kurozu liquid in an earthenware jar over 1 year, a solid residue called Kurozu Moromi is produced. In the present study, we evaluated whether concentrated Kurozu or Kurozu Moromi could ameliorate cognitive dysfunction in the senescence-accelerated P8 mouse. Senescence-accelerated P8 mice were fed 0.25% (w/w concentrated Kurozu or 0.5% (w/w Kurozu Moromi for 4 or 25 weeks. Kurozu suppressed cognitive dysfunction and amyloid accumulation in the brain, while Kurozu Moromi showed a tendency to ameliorate cognitive dysfunction, but the effect was not significant. We hypothesize that concentrated Kurozu has an antioxidant effect; however, the level of lipid peroxidation in the brain did not differ in senescence-accelerated P8 mice. DNA microarray analysis indicated that concentrated Kurozu increased HSPA1A mRNA expression, a protein that prevents protein misfolding and aggregation. The increase in HSPA1A expression by Kurozu was confirmed using quantitative real-time PCR and immunoblotting methods. The suppression of amyloid accumulation by concentrated Kurozu may be associated with HSPA1A induction. However, concentrated Kurozu could not increase HSPA1A expression in mouse primary neurons, suggesting it may not directly affect neurons.

  8. Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

    Science.gov (United States)

    Pourkhodadad, Soheila; Alirezaei, Masoud; Moghaddasi, Mehrnoush; Ahmadvand, Hassan; Karami, Manizheh; Delfan, Bahram; Khanipour, Zahra

    2016-09-01

    Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 μg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

  9. Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

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    Bing Han

    2017-03-01

    Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

  10. Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

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    Murrin L Charles

    2011-03-01

    Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

  11. Reoperation for non-structural valvular dysfunction caused by pannus ingrowth in aortic valve prosthesis.

    Science.gov (United States)

    Oh, Se Jin; Park, Samina; Kim, Jun Sung; Kim, Kyung-Hwan; Kim, Ki Bong; Ahn, Hyuk

    2013-07-01

    The authors' clinical experience is presented of non-structural valvular dysfunction of the prosthetic aortic valve caused by pannus ingrowth during the late postoperative period after previous heart valve surgery. Between January 1999 and April 2012, at the authors' institution, a total of 33 patients underwent reoperation for increased mean pressure gradient of the prosthetic aortic valve. All patients were shown to have pannus ingrowth. The mean interval from the previous operation was 16.7 +/- 4.3 years, and the most common etiology for the previous aortic valve replacement (AVR) was rheumatic valve disease. The mean effective orifice area index (EOAI) of the previous prosthetic valve was 0.97 +/- 0.11 cm2/m2, and the mean pressure gradient on the aortic prosthesis before reoperation was 39.1 +/- 10.7 mmHg. Two patients (6.1%) died in-hospital, and late death occurred in six patients (18.2%). At the first operation, 30 patients underwent mitral or tricuspid valve surgery as a concomitant procedure. Among these operations, mitral valve replacement (MVR) was combined in 24 of all 26 patients with rheumatic valve disease. Four patients underwent pannus removal only while the prosthetic aortic valve was left in place. The mean EOAI after reoperation was significantly increased to 1.16 +/- 0.16 cm2/m2 (p pannus ingrowth was shown in patients with a small EOAI of the prosthetic aortic valve and combined MVR for rheumatic disease. As reoperation for pannus overgrowth showed good clinical outcomes, an aggressive resection of pannus and repeated AVR should be considered in symptomatic patients to avoid the complications of other cardiac diseases.

  12. Angiostatic factors in the pulmonary endarterectomy material from chronic thromboembolic pulmonary hypertension patients cause endothelial dysfunction.

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    Diana Zabini

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a rare disease with persistent thrombotic occlusion or stenosis of the large pulmonary arteries resulting in pulmonary hypertension. Surgical removal of the neointimal layer of these vessels together with the non-resolved thrombus consisting of organized collagen-rich fibrotic areas with partly recanalized regions is the treatment of choice (pulmonary endarterectomy, PEA. The present study investigates endothelial cells isolated from such material as well as factors present in the surgical PEA material, which may contribute to impairment of recanalization and thrombus non-resolution. We observed muscularized vessels and non-muscularized vessels in the PEA material. The isolated endothelial cells from the PEA material showed significantly different calcium homeostasis as compared to pulmonary artery endothelial cells (hPAECs from normal controls. In the supernatant (ELISA as well as on the tissue level (histochemical staining of the PEA material, platelet factor 4 (PF4, collagen type I and interferon-gamma-inducible 10 kD protein (IP-10 were detected. CXCR3, the receptor for PF4 and IP-10, was particularly elevated in the distal parts of the PEA material as compared to human control lung (RT-PCR. PF4, collagen type I and IP-10 caused significant changes in calcium homeostasis and affected the cell proliferation, migration and vessel formation in hPAECs. The presence of angiostatic factors like PF4, collagen type I and IP-10, as recovered from the surgical PEA material from CTEPH patients, may lead to changes in calcium homeostasis and endothelial dysfunction.

  13. UVA Causes Dual Inactivation of Cathepsin B and L Underlying Lysosomal Dysfunction in Human Dermal Fibroblasts

    Science.gov (United States)

    Lamore, Sarah D.; Wondrak, Georg T.

    2013-01-01

    Cutaneous exposure to chronic solar UVA-radiation is a causative factor in photocarcinogenesis and photoaging. Recently, we have identified the thiol-dependent cysteine-protease cathepsin B as a novel UVA-target undergoing photo-oxidative inactivation upstream of autophagic-lysosomal dysfunction in fibroblasts. In this study, we examined UVA effects on a wider range of cathepsins and explored the occurrence of UVA-induced cathepsin inactivation in other cultured skin cell types. In dermal fibroblasts, chronic exposure to non-cytotoxic doses of UVA caused pronounced inactivation of the lysosomal cysteine-proteases cathepsin B and L, effects not observed in primary keratinocytes and occurring only to a minor extent in primary melanocytes. In order to determine if UVA-induced lysosomal impairment requires single or dual inactivation of cathepsin B and/or L, we used a genetic approach (siRNA) to selectively downregulate enzymatic activity of these target cathepsins. Monitoring an established set of protein markers (including LAMP1, LC3-II, and p62) and cell ultrastructural changes detected by electron microscopy, we observed that only dual genetic antagonism (targeting both CTSB and CTSL expression) could mimic UVA-induced autophagic-lysosomal alterations, whereas single knockdown (targeting CTSB or CTSL only) did not display ‘UVA-mimetic’ effects failing to reproduce the UVA-induced phenotype. Taken together, our data demonstrate that chronic UVA inhibits both cathepsin B and L enzymatic activity and that dual inactivation of both enzymes is a causative factor underlying UVA-induced impairment of lysosomal function in dermal fibroblasts. PMID:23603447

  14. Ventral Striatum, but Not Cortical Volume Loss, Is Related to Cognitive Dysfunction in Type 1 Diabetic Patients With and Without Microangiopathy

    NARCIS (Netherlands)

    van Duinkerken, E.; Schoonheim, M.M.; Steenwijk, M.D.; Klein, M.; IJzerman, R.G.; Moll, A.C.; Heymans, M.W.; Snoek, F.J.; Barkhof, F.; Diamant, M.

    2014-01-01

    Objective: Patients with longstanding type 1 diabetes may develop microangiopathy due to high cumulative glucose exposure. Also, chronic hyperglycemia is related to cerebral alterations and cognitive dysfunction. Whether the presence of microangiopathy is conditional to the development of

  15. Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

    Science.gov (United States)

    Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

  16. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD: a meta-analysis.

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    Linying Peng

    Full Text Available BACKGROUND: Postoperative cognitive dysfunction (POCD is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. METHODS: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12.The standardized mean difference (SMD and the 95% confidence interval (95%CI were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. RESULTS: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI] (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies, and interleukin(IL-6 (SMD[95%CI] (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies, but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies. CONCLUSIONS: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

  17. Thermal injury lowers the threshold for radiation-induced neuroinflammation and cognitive dysfunction.

    Science.gov (United States)

    Cherry, Jonathan D; Williams, Jacqueline P; O'Banion, M Kerry; Olschowka, John A

    2013-10-01

    The consequences of radiation exposure alone are relatively well understood, but in the wake of events such as the World War II nuclear detonations and accidents such as Chernobyl, other critical factors have emerged that can substantially affect patient outcome. For example, ~70% of radiation victims from Hiroshima and Nagasaki received some sort of additional traumatic injury, the most common being thermal burn. Animal data has shown that the addition of thermal insult to radiation results in increased morbidity and mortality. To explore possible synergism between thermal injury and radiation on brain, C57BL/6J female mice were exposed to either 0 or 5 Gy whole-body gamma irradiation. Irradiation was immediately followed by a 10% total-body surface area full thickness thermal burn. Mice were sacrificed 6 h, 1 week or 6 month post-injury and brains and plasma were harvested for histology, mRNA analysis and cytokine ELISA. Plasma analysis revealed that combined injury synergistically upregulates IL-6 at acute time points. Additionally, at 6 h, combined injury resulted in a greater upregulation of the vascular marker, ICAM-1 and TNF-α mRNA. Enhanced activation of glial cells was also observed by CD68 and Iba1 immunohistochemistry at all time points. Additionally, doublecortin staining at 6 months showed reduced neurogenesis in all injury conditions. Finally, using a novel object recognition test, we observed that only mice with combined injury had significant learning and memory deficits. These results demonstrate that thermal injury lowers the threshold for radiation-induced neuroinflammation and long-term cognitive dysfunction.

  18. Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study.

    Science.gov (United States)

    Hart, John; Kraut, Michael A; Womack, Kyle B; Strain, Jeremy; Didehbani, Nyaz; Bartz, Elizabeth; Conover, Heather; Mansinghani, Sethesh; Lu, Hanzhang; Cullum, C Munro

    2013-03-01

    OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy

  19. Is the age at menopause a cause of sexual dysfunction? A Brazilian population-based study.

    Science.gov (United States)

    Lett, Caio; Valadares, Ana L R; Baccaro, Luiz F; Pedro, Adriana O; Filho, Jeffrey L; Lima, Marcelo; Costa-Paiva, Lucia

    2018-01-01

    The aim of the study was to evaluate the association between age at menopause and sexual dysfunction and the components of sexual function in postmenopausal women. In this cross-sectional population-based study, data of 540 women aged 45 to 60 years regarding the age they were when they achieved menopause and its association with sexual dysfunction (evaluated using the Short Personal Experiences Questionnaire) were obtained through interviews. We assessed the data for associations between age at menopause and sexual dysfunction and demographic, behavioral, and clinical characteristics. Age at menopause was not associated with sexual dysfunction. Arousal (dysfunction) was the only component of sexual function that was associated with premature ovarian insufficiency (POI) and early menopause (P = 0.01). It was reported by 64.2% of women with POI (women 45 years, respectively (P = 0.04). In women with POI or early menopause, Poisson regression analysis showed that having a partner with sexual problems (prevalence ratio [PR] = 6.6; 95% CI: 3.3-13,2; P POI. The major factors affecting this association were having a partner with sexual problems, dyspareunia, and no satisfaction with the partner as a lover. These findings highlight the importance of evaluating partner problems and improving lubrication in these groups of women.

  20. Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory.

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    Kei Hori

    Full Text Available Mutations in the Autism susceptibility candidate 2 gene (AUTS2 have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and schizophrenia. We previously demonstrated that the cytoplasmic AUTS2 acts as an upstream factor for the Rho family small GTPase Rac1 and Cdc42 that regulate the cytoskeletal rearrangements in neural cells. Moreover, genetic ablation of the Auts2 gene in mice has resulted in defects in neuronal migration and neuritogenesis in the developing cerebral cortex caused by inactivation of Rac1-signaling pathway, suggesting that AUTS2 is required for neural development. In this study, we conducted a battery of behavioral analyses on Auts2 heterozygous mutant mice to examine the involvement of Auts2 in adult cognitive brain functions. Auts2-deficient mice displayed a decrease in exploratory behavior as well as lower anxiety-like behaviors in the absence of any motor dysfunction. Furthermore, the capability for novel object recognition and cued associative memory were impaired in Auts2 mutant mice. Social behavior and sensory motor gating functions were, however, normal in the mutant mice as assessed by the three-chamber test and prepulse inhibition test, respectively. Together, our findings indicate that AUTS2 is critical for the acquisition of neurocognitive function.

  1. Tadalafil reversal of sexual dysfunction caused by serotonin enhancing medications in women.

    Science.gov (United States)

    Ashton, Adam Keller; Weinstein, Wendy

    2006-01-01

    Sexual dysfunction is a common side effect of many antidepressants, especially those that increase serotonin. Many strategies have been reported to assist patients in minimizing impairment, with variable degrees of success. One of the newer approaches is to augment with phosphodiesterase type-5 inhibitors. Our report using the most recently released agent in this class, tadalafil is the first demonstrating potential benefit in women. We report here of three women who derived benefit from using 20 mg of tadalafil before anticipated sexual activity to reverse medication-induced sexual dysfunction. Tadalafil utility was maintained over time and was well tolerated.

  2. Optimising screening for cognitive dysfunction in bipolar disorder: Validation and evaluation of objective and subjective tools

    DEFF Research Database (Denmark)

    Jensen, Johan Høy; Støttrup, Mette Marie; Nayberg, Emilie

    2015-01-01

    by correlation with established objective and subjective cognitive measures, and decision validity was determined with Receiver-Operating-Characteristic analyses. Correlations and linear regression analyses were conducted to determine the associations between objective and subjective cognitive impairment......Introduction Cognitive impairment is common in bipolar disorder and contributes to socio-occupational difficulties. The objective was to validate and evaluate instruments to screen for and monitor cognitive impairments, and improve the understanding of the association between cognitive measures...

  3. Basal ganglia calcification as a putative cause for cognitive decline

    OpenAIRE

    de Oliveira, João Ricardo Mendes; de Oliveira, Matheus Fernandes

    2013-01-01

    ABSTRACT Basal ganglia calcifications (BGC) may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological an...

  4. Urinary dysfunction after rectal cancer treatment is mainly caused by surgery

    NARCIS (Netherlands)

    Lange, M. M.; Maas, C. P.; Marijnen, C. A. M.; Wiggers, T.; Rutten, H. J.; Kranenbarg, E. Klein; van de Velde, C. J. H.

    Background. Urinary dysfunction (UD) is common after rectal cancer treatment, but the contribution of each treatment component (surgery and radiotherapy) to its development remains unclear. This study aimed to evaluate UD during 5 years after total mesorectal excision (TME) and to investigate the

  5. The Effectiveness of Mindfulness-Based Cognitive Group Therapy in Reducing Negative Automatic Thoughts and Dysfunctional Attitudes in Cancer Patients

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    Fatemeh Mehdipour

    2017-06-01

    Full Text Available Background This study aimed to evaluate the effectiveness of mindfulness-based cognitive group therapy (MBCT in reducing negative automatic thoughts and dysfunctional attitudes in cancer patients. Methods The study was an applied and quasi-experimental research conducted by pre- and post-testing. The sample consisted of 30 cancer patients selected by purposive sampling and randomly placed in the control and the experimental group (15 individuals per group. The members of both groups filled out the automatic thoughts questionnaire (ATQ and the dysfunctional attitudes scale (DAS-26 at the pre- and the post-test stage. The collected data were analyzed by the SPSS software and multivariate analysis of covariance (MANCOVA tests. Results The results indicated that MBCT significantly reduced negative automatic thoughts (F = 126.15, P < 0.01 and dysfunctional attitudes (F = 179.53, P < 0.01 in the experimental group at the post-test stage in comparison to the control group. Conclusions Based on the results of this study, it is essential that therapeutic centers and support forums related to patients with refractory disorders use MBCT in their programs for reducing negative automatic thoughts and dysfunctional attitudes.

  6. Child, parent and family dysfunction as predictors of outcome in cognitive-behavioral treatment of antisocial children.

    Science.gov (United States)

    Kazdin, A E

    1995-03-01

    The present study examined factors that predicted favorable treatment outcomes among clinically referred conduct problem children (N = 105, ages 7-13) who received cognitive-behavioral treatment. Three domains (severity and breadth of child impairment, parent stress and psychopathology and family dysfunction) assessed at pretreatment were predicted to affect treatment outcome. The results only partially supported the prediction. Less dysfunction in each of the domains predicted who responded favorably to treatment on parent ratings of deviance and prosocial functioning but not on teacher ratings of these outcomes. The findings have implications for identifying youths who respond to available treatments. The results also underscore fundamental questions about the assessment of treatment effects and the criteria for evaluating outcome.

  7. Protective effect of rutin on cognitive impairment caused by phenytoin

    Science.gov (United States)

    Dubey, Shagun; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

    2015-01-01

    Objective: To study the effect of the co-administration of phenytoin (PHT) and rutin in comparison with PHT and piracetam (PIM) on seizure control, cognitive, and motor functions in mice. Materials and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the co-administration of PHT and PIM on convulsions. Cognitive functions in mice were assessed by a spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetyl-cholinesterase (AChE) activity was also estimated. Statistical Analysis: The expression of data was done as mean ± standard error of the mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett's test. P < 0.05 was considered significant. Results: The study showed that rutin when co-administered with PHT, significantly reversed PHT-induced reduction in spontaneous alternation without altering the efficacy of PHT against ICES, in both acute and chronic studies. Further, it also reversed PHT-induced increase in AChE activity. Conclusion: Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy. PMID:26729954

  8. A randomized trial of videoconference-delivered cognitive behavioral therapy for survivors of breast cancer with self-reported cognitive dysfunction.

    Science.gov (United States)

    Ferguson, Robert J; Sigmon, Sandra T; Pritchard, Andrew J; LaBrie, Sharon L; Goetze, Rachel E; Fink, Christine M; Garrett, A Merrill

    2016-06-01

    Long-term chemotherapy-related cognitive dysfunction (CRCD) affects a large number of cancer survivors. To the authors' knowledge, to date there is no established treatment for this survivorship problem. The authors herein report results of a small randomized controlled trial of a cognitive behavioral therapy (CBT), Memory and Attention Adaptation Training (MAAT), compared with an attention control condition. Both treatments were delivered over a videoconference device. A total of 47 survivors of female breast cancer who reported CRCD were randomized to MAAT or supportive therapy and were assessed at baseline, after treatment, and at 2 months of follow-up. Participants completed self-report measures of cognitive symptoms and quality of life and a brief telephone-based neuropsychological assessment. MAAT participants made gains in perceived (self-reported) cognitive impairments (P = .02), and neuropsychological processing speed (P = .03) compared with supportive therapy controls. A large MAAT effect size was observed at the 2-month follow-up with regard to anxiety concerning cognitive problems (Cohen's d for standard differences in effect sizes, 0.90) with medium effects noted in general function, fatigue, and anxiety. Survivors rated MAAT and videoconference delivery with high satisfaction. MAAT may be an efficacious psychological treatment of CRCD that can be delivered through videoconference technology. This research is important because it helps to identify a treatment option for survivors that also may improve access to survivorship services. Cancer 2016;122:1782-91. © 2016 American Cancer Society. © 2016 American Cancer Society.

  9. [Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

    Science.gov (United States)

    Ostrowska-Nawarycz, L; Rapacka, E; Baszczyński, J; Górski, P; Czajka, J; Makowski, M; Kudzin, A

    2000-04-01

    The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

  10. Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.

    Science.gov (United States)

    van Zutphen, Tim; Ciapaite, Jolita; Bloks, Vincent W; Ackereley, Cameron; Gerding, Albert; Jurdzinski, Angelika; de Moraes, Roberta Allgayer; Zhang, Ling; Wolters, Justina C; Bischoff, Rainer; Wanders, Ronald J; Houten, Sander M; Bronte-Tinkew, Dana; Shatseva, Tatiana; Lewis, Gary F; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M; Jonker, Johan W; Kim, Peter K; Bandsma, Robert H J

    2016-12-01

    Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. Peroxisomes and mitochondria play key roles in various hepatic metabolic functions including lipid metabolism and energy production. To investigate the involvement of these organelles in the mechanisms underlying malnutrition-induced hepatic dysfunction we developed a rat model of malnutrition. Weanling rats were placed on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Peroxisomal and mitochondrial structural features were characterized using immunofluorescence and electron microscopy. Mitochondrial function was assessed using high-resolution respirometry. A novel targeted quantitative proteomics method was applied to analyze 47 mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle and fatty acid β-oxidation pathways. Low protein diet-fed rats developed hypoalbuminemia and hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated peroxisomal dysfunction. This was followed by changes in mitochondrial ultrastructure and increased mitochondrial content. Mitochondrial function was impaired due to multiple defects affecting respiratory chain complex I and IV, pyruvate uptake and several β-oxidation enzymes, leading to strongly reduced hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial β-oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. Malnutrition leads to severe impairments in hepatic peroxisomal and mitochondrial function, and hepatic metabolic dysfunction. We discuss the potential future implications of our findings for the clinical management of malnourished children. Severe malnutrition in children is associated with metabolic disturbances

  11. A randomised controlled trial of adjunctive yoga and adjunctive physical exercise training for cognitive dysfunction in schizophrenia.

    Science.gov (United States)

    Bhatia, Triptish; Mazumdar, Sati; Wood, Joel; He, Fanyin; Gur, Raquel E; Gur, Ruben C; Nimgaonkar, Vishwajit L; Deshpande, Smita N

    2017-04-01

    Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking. Aims A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study. Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of 'attention' in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm. Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (pattention domain showed greater improvement than TAU alone at 6-month follow-up (pattention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.

  12. Is Internet Pornography Causing Sexual Dysfunctions? A Review with Clinical Reports

    Science.gov (United States)

    Park, Brian Y.; Wilson, Gary; Berger, Jonathan; Christman, Matthew; Reina, Bryn; Bishop, Frank; Klam, Warren P.; Doan, Andrew P.

    2016-01-01

    Traditional factors that once explained men’s sexual difficulties appear insufficient to account for the sharp rise in erectile dysfunction, delayed ejaculation, decreased sexual satisfaction, and diminished libido during partnered sex in men under 40. This review (1) considers data from multiple domains, e.g., clinical, biological (addiction/urology), psychological (sexual conditioning), sociological; and (2) presents a series of clinical reports, all with the aim of proposing a possible direction for future research of this phenomenon. Alterations to the brain's motivational system are explored as a possible etiology underlying pornography-related sexual dysfunctions. This review also considers evidence that Internet pornography’s unique properties (limitless novelty, potential for easy escalation to more extreme material, video format, etc.) may be potent enough to condition sexual arousal to aspects of Internet pornography use that do not readily transition to real-life partners, such that sex with desired partners may not register as meeting expectations and arousal declines. Clinical reports suggest that terminating Internet pornography use is sometimes sufficient to reverse negative effects, underscoring the need for extensive investigation using methodologies that have subjects remove the variable of Internet pornography use. In the interim, a simple diagnostic protocol for assessing patients with porn-induced sexual dysfunction is put forth. PMID:27527226

  13. Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2017-01-01

    Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl 3 ) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO 4 ) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

  14. Tinnitus and other auditory problems - occupational noise exposure below risk limits may cause inner ear dysfunction.

    Science.gov (United States)

    Lindblad, Ann-Cathrine; Rosenhall, Ulf; Olofsson, Åke; Hagerman, Björn

    2014-01-01

    The aim of the investigation was to study if dysfunctions associated to the cochlea or its regulatory system can be found, and possibly explain hearing problems in subjects with normal or near-normal audiograms. The design was a prospective study of subjects recruited from the general population. The included subjects were persons with auditory problems who had normal, or near-normal, pure tone hearing thresholds, who could be included in one of three subgroups: teachers, Education; people working with music, Music; and people with moderate or negligible noise exposure, Other. A fourth group included people with poorer pure tone hearing thresholds and a history of severe occupational noise, Industry. Ntotal = 193. The following hearing tests were used: - pure tone audiometry with Békésy technique, - transient evoked otoacoustic emissions and distortion product otoacoustic emissions, without and with contralateral noise; - psychoacoustical modulation transfer function, - forward masking, - speech recognition in noise, - tinnitus matching. A questionnaire about occupations, noise exposure, stress/anxiety, muscular problems, medication, and heredity, was addressed to the participants. Forward masking results were significantly worse for Education and Industry than for the other groups, possibly associated to the inner hair cell area. Forward masking results were significantly correlated to louder matched tinnitus. For many subjects speech recognition in noise, left ear, did not increase in a normal way when the listening level was increased. Subjects hypersensitive to loud sound had significantly better speech recognition in noise at the lower test level than subjects not hypersensitive. Self-reported stress/anxiety was similar for all groups. In conclusion, hearing dysfunctions were found in subjects with tinnitus and other auditory problems, combined with normal or near-normal pure tone thresholds. The teachers, mostly regarded as a group exposed to noise

  15. Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

    Science.gov (United States)

    Maggi, Mario; Buvat, Jaques; Corona, Giovanni; Guay, André; Torres, Luiz Otavio

    2013-03-01

    Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in

  16. Tinnitus and other auditory problems - occupational noise exposure below risk limits may cause inner ear dysfunction.

    Directory of Open Access Journals (Sweden)

    Ann-Cathrine Lindblad

    Full Text Available The aim of the investigation was to study if dysfunctions associated to the cochlea or its regulatory system can be found, and possibly explain hearing problems in subjects with normal or near-normal audiograms. The design was a prospective study of subjects recruited from the general population. The included subjects were persons with auditory problems who had normal, or near-normal, pure tone hearing thresholds, who could be included in one of three subgroups: teachers, Education; people working with music, Music; and people with moderate or negligible noise exposure, Other. A fourth group included people with poorer pure tone hearing thresholds and a history of severe occupational noise, Industry. Ntotal = 193. The following hearing tests were used: - pure tone audiometry with Békésy technique, - transient evoked otoacoustic emissions and distortion product otoacoustic emissions, without and with contralateral noise; - psychoacoustical modulation transfer function, - forward masking, - speech recognition in noise, - tinnitus matching. A questionnaire about occupations, noise exposure, stress/anxiety, muscular problems, medication, and heredity, was addressed to the participants. Forward masking results were significantly worse for Education and Industry than for the other groups, possibly associated to the inner hair cell area. Forward masking results were significantly correlated to louder matched tinnitus. For many subjects speech recognition in noise, left ear, did not increase in a normal way when the listening level was increased. Subjects hypersensitive to loud sound had significantly better speech recognition in noise at the lower test level than subjects not hypersensitive. Self-reported stress/anxiety was similar for all groups. In conclusion, hearing dysfunctions were found in subjects with tinnitus and other auditory problems, combined with normal or near-normal pure tone thresholds. The teachers, mostly regarded as a group

  17. Comparing the efficacy of combined Mindfulness Based Cognitive Therapy with Cognitive Behavioral Therapy and Traditional Cognitive Behavior Therapy in reducing dysfunctional attitudes of patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Abdollah omidi

    2014-02-01

    Results: Dysfunctional attitudes scores and depression symptoms significantly decreased in combined MBCT with CBT group, while in the TAU group, there was no significant difference between pre-test and post-test. Conclusion: MBCT combined with CBT has similar effects to classic CBT and it can lead to reducing dysfunctional attitudes and depression symptoms.

  18. Cognitive and neural correlates of depression-like behaviour in socially defeated mice: an animal model of depression with cognitive dysfunction.

    Science.gov (United States)

    Yu, Tao; Guo, Ming; Garza, Jacob; Rendon, Samantha; Sun, Xue-Li; Zhang, Wei; Lu, Xin-Yun

    2011-04-01

    Human depression is associated with cognitive deficits. It is critical to have valid animal models in order to investigate mechanisms and treatment strategies for these associated conditions. The goal of this study was to determine the association of cognitive dysfunction with depression-like behaviour in an animal model of depression and investigate the neural circuits underlying the behaviour. Mice that were exposed to social defeat for 14 d developed depression-like behaviour, i.e. anhedonia and social avoidance as indicated by reduced sucrose preference and decreased social interaction. The assessment of cognitive performance of defeated mice demonstrated impaired working memory in the T-maze continuous alternation task and enhanced fear memory in the contextual and cued fear-conditioning tests. In contrast, reference learning and memory in the Morris water maze test were intact in defeated mice. Neuronal activation following chronic social defeat was investigated by c-fosin-situ hybridization. Defeated mice exhibited preferential neural activity in the prefrontal cortex, cingulate cortex, hippocampal formation, septum, amygdala, and hypothalamic nuclei. Taken together, our results suggest that the chronic social defeat mouse model could serve as a valid animal model to study depression with cognitive impairments. The patterns of neuronal activation provide a neural basis for social defeat-induced changes in behaviour.

  19. Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons

    Science.gov (United States)

    Ito, Hiroyuki; Uchida, Tokujiro; Makita, Koshi

    2015-01-01

    Purpose Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated. Methods Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy. Results Twenty-four-hour exposure of iPSC-derived neurons to 500 μM ketamine resulted in a 40% increase in caspase 3/7 activity (P ketamine (100 μM) decreased the ATP level (22%, P ketamine concentration, which suggests that mitochondrial dysfunction preceded ROS generation and caspase activation. Conclusions We established an in vitro model for assessing the neurotoxicity of ketamine in iPSC-derived neurons. The present data indicate that the initial mitochondrial dysfunction and autophagy may be related to its inhibitory effect on the mitochondrial electron transport system, which underlies ketamine-induced neural toxicity. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons. PMID:26020236

  20. PiB fails to map amyloid deposits in cerebral cortex of aged dogs with canine cognitive dysfunction

    DEFF Research Database (Denmark)

    Fast, Rikke; Rodell, Anders; Gjedde, Albert

    2013-01-01

    to the understanding of AD. However, the sensitivity of the biomarker Pittsburgh Compound B (PiB) to the presence of Aβ in humans and in other mammalian species is in doubt. To test the sensitivity and assess the distribution of Aβ in dog brain, we mapped the brains of dogs with signs of CCD (n = 16) and a control......]PiB in the cerebellum, compared to the cerebral cortex. Retention in the cerebellum is at variance with evidence from brains of humans with AD. To confirm the lack of sensitivity, we stained two dog brains with the immunohistochemical marker 6E10, which is sensitive to the presence of both Aβ and Aβ precursor protein......Dogs with Canine Cognitive Dysfunction (CCD) accumulate amyloid beta (Aβ) in the brain. As the cognitive decline and neuropathology of these old dogs share features with Alzheimer's disease (AD), the relation between Aβ and cognitive decline in animal models of cognitive decline is of interest...

  1. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Yingchun Wang

    2015-01-01

    Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

  2. Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi; Hidaka, Makoto; Masaki, Haruhiko, E-mail: amasaki@mail.ecc.u-tokyo.ac.jp

    2014-08-15

    Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.

  3. Urinary alpha 1-microglobulin as an indicator protein of renal tubular dysfunction caused by environmental cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tohyama, C.; Kobayashi, E.; Saito, H.; Sugihara, N.; Nakano, A.; Mitane, Y.

    1986-06-01

    An epidemiologic investigation was carried out to clarify the significance of the urinary excretion of alpha 1-microglobulin (alpha 1-MG) in people aged 50 years and over living in a Cd-polluted area in Japan. Approximately 80% of the population participated in the health examination. The urinary and serum levels and the relative clearance of alpha 1-MG to creatinine clearance were compared with various parameters (age, urinary beta 2-microglobulin (beta 2-MG), total protein, Cd, Cu and Zn, serum beta 2-MG, creatinine and blood urea nitrogen and relative clearances of alpha 1-MG, beta 2-MG, inorganic phosphate and uric acid). It was found that the urinary excretion of alpha 1-MG is closely associated with the urinary Cd and Cu and with the indices of renal dysfunction listed above. These results suggest that the urinary alpha 1-MG level markedly reflects a degree of proximal tubular dysfunction and that it may be useful as one of the screening measures for proximal tubular dysfunction caused by environmental Cd exposure.

  4. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

    Science.gov (United States)

    Amenta, F; Tayebati, S K

    2008-01-01

    Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.

  5. Esophageal dysfunction as a cause of angina pectoris ("linked angina"): does it exist?

    NARCIS (Netherlands)

    Lam, H. G.; Dekker, W.; Kan, G.; van Berg Henegouwen, G. P.; Smout, A. J.

    1994-01-01

    PURPOSE: The differentiation between cardiac and esophageal causes of retrosternal chest pain is notoriously difficult. Theoretically, cardiac and esophageal causes may coexist. It has also been reported that gastroesophageal reflux and esophageal motor abnormalities may elicit myocardial ischemia

  6. Measuring illness insight in patients with alcohol-related cognitive dysfunction using the Q8 questionnaire: a validation study

    Directory of Open Access Journals (Sweden)

    Walvoort SJW

    2016-07-01

    Full Text Available Serge JW Walvoort,1–3 Paul T van der Heijden,3,4 Roy PC Kessels,1,2,5 Jos IM Egger1–3,6 1Centre of Excellence for Korsakoff and Alcohol-Related Cognitive Disorders, Vincent van Gogh Institute for Psychiatry, Venray, 2Donders Institute for Brain, Cognition and Behaviour, 3Behavioural Science Institute, Radboud University, Nijmegen, 4Reinier van Arkel Mental Health Institute, ‘s-Hertogenbosch, 5Department of Medical Psychology, Radboud University Medical Center, Nijmegen, 6Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, the Netherlands Aim: Impaired illness insight may hamper treatment outcome in patients with alcohol-related cognitive deficits. In this study, a short questionnaire for the assessment of illness insight (eg, the Q8 was investigated in patients with Korsakoff’s syndrome (KS and in alcohol use disorder (AUD patients with mild neurocognitive deficits. Methods: First, reliability coefficients were computed and internal structure was investigated. Then, comparisons were made between patients with KS and patients with AUD. Furthermore, correlations with the Dysexecutive Questionnaire (DEX were investigated. Finally, Q8 total scores were correlated with neuropsychological tests for processing speed, memory, and executive function. Results: Internal consistency of the Q8 was acceptable (ie, Cronbach’s α =0.73. The Q8 items represent one factor, and scores differ significantly between AUD and KS patients. The Q8 total score, related to the DEX discrepancy score and scores on neuropsychological tests as was hypothesized, indicates that a higher degree of illness insight is associated with a higher level of cognitive functioning. Conclusion: The Q8 is a short, valid, and easy-to-administer questionnaire to reliably assess illness insight in patients with moderate-to-severe alcohol-related cognitive dysfunction. Keywords: illness insight, anosognosia, alcohol use disorder, Korsakoff

  7. Causal mechanisms of subjective cognitive dysfunction in schizophrenic and depressed patients

    NARCIS (Netherlands)

    van den Bosch, RJ; Rombouts, RP

    We examined causal mechanisms of subjective cognitive (dis)abilities in schizophrenic and depressed patients, and in patient and normal control groups. This exploratory study included objective cognitive performance (Continuous Performance Task) as well as mood and mental effort ratings. Self-report

  8. Capillary dysfunction in Alzheimer’s disease correlates with cognitive decline

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Gyldensted, Louise; Nagenthiraja, Kartheeban

    Aim: We hypothesized that capillary dysfunction exists in Alzheimer’s disease (AD) and this can be determined by a relative increase in capillary transit time heterogeneity (CTH) in cortical gray matter compared to age-matched controls. Methods: We used dynamic susceptibility contrast (DSC...

  9. PTSD symptom severity relates to cognitive and psycho-social dysfunctioning - a study with Congolese refugees in Uganda.

    Science.gov (United States)

    Ainamani, Herbert E; Elbert, Thomas; Olema, David K; Hecker, Tobias

    2017-01-01

    Background : In the ongoing conflict in the Democratic Republic of the Congo (DRC), civilians have been heavily exposed to traumatic stressors. Traumatizing experiences cumulatively heighten the risk for trauma-related disorders, and with it affect cognitive and psycho-social functioning. Objectives : We aimed at investigating the association between trauma-related disorders and cognitive and psycho-social functioning and hypothesized that PTSD symptom severity would negatively correlate with executive functioning, working memory and psycho-social functioning in everyday life. Method : In total, 323 Congolese refugees (mean age: 31.3 years) who arrived in the Ugandan Nakivale refugee settlement after January 2012 were assessed regarding their exposure to traumatic events, PTSD symptom severity (posttraumatic symptom scale interview), executive functioning (Tower of London), working memory performance (Corsi block tapping task) and psycho-social dysfunctioning (Luo functioning scale). Results : Hierarchical regression analyses indicated a significant negative association between PTSD symptom severity and working memory (β = -0.32, p  psycho-social functioning in everyday life was positively related with PTSD symptom severity (β = 0.70, p  psycho-social dysfunctioning (β = 0.09, p  > 0.05). Conclusion : Trauma survivors not only suffer from the core PTSD symptoms but also from impaired cognitive functioning. PTSD symptom severity seems furthermore to be related to impaired psycho-social functioning. Our findings suggest that trauma-related mental health problems may heighten the risk for poverty and lack of prospect and further aggravate the consequences of war and conflict.

  10. PTSD symptom severity relates to cognitive and psycho-social dysfunctioning – a study with Congolese refugees in Uganda

    Science.gov (United States)

    Ainamani, Herbert E.; Elbert, Thomas; Olema, David K.; Hecker, Tobias

    2017-01-01

    ABSTRACT Background: In the ongoing conflict in the Democratic Republic of the Congo (DRC), civilians have been heavily exposed to traumatic stressors. Traumatizing experiences cumulatively heighten the risk for trauma-related disorders, and with it affect cognitive and psycho-social functioning. Objectives: We aimed at investigating the association between trauma-related disorders and cognitive and psycho-social functioning and hypothesized that PTSD symptom severity would negatively correlate with executive functioning, working memory and psycho-social functioning in everyday life. Method: In total, 323 Congolese refugees (mean age: 31.3 years) who arrived in the Ugandan Nakivale refugee settlement after January 2012 were assessed regarding their exposure to traumatic events, PTSD symptom severity (posttraumatic symptom scale interview), executive functioning (Tower of London), working memory performance (Corsi block tapping task) and psycho-social dysfunctioning (Luo functioning scale). Results: Hierarchical regression analyses indicated a significant negative association between PTSD symptom severity and working memory (β = –0.32, p psycho-social functioning in everyday life was positively related with PTSD symptom severity (β = 0.70, p psycho-social dysfunctioning (β = 0.09, p > 0.05). Conclusion: Trauma survivors not only suffer from the core PTSD symptoms but also from impaired cognitive functioning. PTSD symptom severity seems furthermore to be related to impaired psycho-social functioning. Our findings suggest that trauma-related mental health problems may heighten the risk for poverty and lack of prospect and further aggravate the consequences of war and conflict. PMID:28326164

  11. Cognitive dysfunction, affective states and vulnerability to nicotine addiction: a multifactorial perspective

    Directory of Open Access Journals (Sweden)

    Benoit Forget

    2016-09-01

    Full Text Available Although smoking prevalence has declined in recent years, certain subpopulations continue to smoke at disproportionately high rates and show resistance to cessation treatments. Individuals showing cognitive and affective impairments such as emotional distress and deficits in attention, memory and inhibitory control, particularly in the context of psychiatric conditions such as ADHD, schizophrenia and mood disorders, are at higher risk for tobacco addiction. Nicotine has been shown to improve cognitive and emotional processing in some conditions, including during tobacco abstinence. Self-medication of cognitive deficits or negative affect has been proposed to underlie high rates of tobacco smoking among people with psychiatric disorders. However, pre-existing cognitive and mood disorders may also influence the development and maintenance of nicotine dependence, by biasing nicotine-induced alterations in information processing and associative learning, decision making, and inhibitory control. Here we discuss the potential forms of contribution of cognitive and affective deficits to nicotine addiction-related processes, by reviewing major clinical and preclinical studies investigating either the pro-cognitive and therapeutic action of nicotine or the putative primary role of cognitive and emotional impairments in addiction-like features.

  12. Overweight causes left ventricular diastolic asynchrony and diastolic dysfunction: a study based on speckle tracking echocardiography in healthy subjects.

    Science.gov (United States)

    Nakabachi, Masahiro; Mikami, Taisei; Okada, Kazunori; Onozuka, Hisao; Kaga, Sanae; Inoue, Mamiko; Yokoyama, Shinobu; Nishida, Mutsumi; Shimizu, Chikara; Matsuno, Kazuhiko; Iwano, Hiroyuki; Yamada, Satoshi; Tsutsui, Hiroyuki

    2012-09-01

    Left ventricular (LV) diastolic dysfunction is often observed in healthy subjects and can be a cause of heart failure with preserved ejection fraction (EF). We aimed to investigate the role of LV diastolic asynchrony as a cause of diastolic dysfunction in healthy subjects. In 40 healthy subjects, two-dimensional speckle tracking imaging (2DSTI) was performed to measure the peak early diastolic longitudinal strain rates (Esr) of the apical, mid-ventricular, and basal segments of the septum and posterior wall. A mean value of the Esr of the 6 segments (mEsr) was calculated. The time from aortic valve closure to the Esr was measured for each segment, and the standard deviation (SDTEsr) was calculated. The peak global early diastolic strain rate (gEsr) was measured with a region of interest (ROI) on the whole LV myocardium. LV flow propagation velocity (FPV) was measured using conventional Doppler techniques. SDTEsr was not correlated with age, but was significantly correlated with body mass index (BMI) (r = 0.41, p < 0.01). Although no significant correlation was observed between mEsr and FPV, gEsr and SDTEsr significantly correlated with FPV (r = 0.41, p < 0.01; r = -0.54, p < 0.001). As a result of the multiple regression analysis, SDTEsr was the single determinant of FPV. Diastolic asynchrony, associated with overweight but not with aging, may contribute to diastolic dysfunction in healthy subjects.

  13. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events

    DEFF Research Database (Denmark)

    Selmer, Christian; Olesen, Jonas Bjerring; Hansen, Morten Lock

    2014-01-01

    hypothyroidism with TSH of 5-10 mIU/L [IRR 0.92 (95% CI 0.86-0.98)]. CONCLUSIONS: Heart failure is the leading cause of an increased cardiovascular mortality in both overt and subclinical hyperthyroidism. Subclinical hypothyroidism with TSH 5-10 mIU/L might be associated with a lower risk of all-cause mortality....

  14. Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway

    Directory of Open Access Journals (Sweden)

    Ramesh Vijay

    2012-05-01

    Full Text Available Abstract Background Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice. Methods The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice. In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody. Results Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity. Conclusions Taken together

  15. The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction

    OpenAIRE

    Thompson, Hannah E; Almaghyuli, Azizah; Noonan, Krist A.; Barak, Ohr; Lambon Ralph, Matthew; Jefferies, Elizabeth

    2018-01-01

    Semantic cognition, as described by the Controlled Semantic Cognition (CSC) framework (Rogers, Patterson, Jefferies, & Lambon Ralph, 2015), involves two key components: activation of coherent, generalizable concepts within a heteromodal ‘hub’ in combination with modality-specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time- and task- appropriate behaviour. Executive-semantic goal representations, largely supported by executive...

  16. The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction

    OpenAIRE

    Thompson, Hannah; Almaghyuli, Azizah; Noonan, Krist A.; barak, Ohr; Lambon Ralph, Matthew A.; Jefferies, Elizabeth

    2018-01-01

    Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., 2015, Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal ‘hub’ in combination with modality-specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time- and task-appropriate behaviour. Executive–semantic goal representations, largely supported by executive regions ...

  17. Effect of virtual reality on cognitive dysfunction in patients with brain tumor.

    Science.gov (United States)

    Yang, Seoyon; Chun, Min Ho; Son, Yu Ri

    2014-12-01

    To investigate whether virtual reality (VR) training will help the recovery of cognitive function in brain tumor patients. Thirty-eight brain tumor patients (19 men and 19 women) with cognitive impairment recruited for this study were assigned to either VR group (n=19, IREX system) or control group (n=19). Both VR training (30 minutes a day for 3 times a week) and computer-based cognitive rehabilitation program (30 minutes a day for 2 times) for 4 weeks were given to the VR group. The control group was given only the computer-based cognitive rehabilitation program (30 minutes a day for 5 days a week) for 4 weeks. Computerized neuropsychological tests (CNTs), Korean version of Mini-Mental Status Examination (K-MMSE), and Korean version of Modified Barthel Index (K-MBI) were used to evaluate cognitive function and functional status. The VR group showed improvements in the K-MMSE, visual and auditory continuous performance tests (CPTs), forward and backward digit span tests (DSTs), forward and backward visual span test (VSTs), visual and verbal learning tests, Trail Making Test type A (TMT-A), and K-MBI. The VR group showed significantly (p<0.05) better improvements than the control group in visual and auditory CPTs, backward DST and VST, and TMT-A after treatment. VR training can have beneficial effects on cognitive improvement when it is combined with computer-assisted cognitive rehabilitation. Further randomized controlled studies with large samples according to brain tumor type and location are needed to investigate how VR training improves cognitive impairment.

  18. New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function

    OpenAIRE

    Jeon, Won Je; Sumiyoshi, Tomiki; Kurachi, Masayoshi

    2015-01-01

    Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive ?-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of exc...

  19. Understanding and remediating social-cognitive dysfunctions in patients with serious mental illness using relational frame theory

    Directory of Open Access Journals (Sweden)

    Annemieke eHendriks

    2016-02-01

    Full Text Available Impairments in social cognition and perspective-taking play an important role in the psychopathology and social functioning of individuals with social anxiety, autism or schizophrenia-spectrum disorders, among other clinical presentations. Perspective-taking has mostly been studied using the concept of Theory of Mind (ToM, which describes the sequential development of these skills in young children, as well as clinical populations experiencing perspective-taking difficulties. Several studies mention positive results of Theory of Mind based training programs, however, the precise processes involved in the achievement of these improvements are difficult to determine. Relational Frame Theory (RFT is a modern behavioural account of complex cognitive functions, and is argued to provide a more precise approach to the assessment and training of perspective-taking, among other relational skills. Results of RFT-based studies of perspective-taking in developmental and clinical settings are discussed. The development of training methods targeting perspective-taking deficits from an RFT point of view appears to provide promising applications for the enhancement of current treatments of people with social-cognitive dysfunctions.

  20. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

    2014-01-01

    To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism. PMID:24672632

  1. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  2. Cerebral metabolic alterations and cognitive dysfunction in children with chronic kidney disease using Magnetic Resonance Spectroscopy and Wechsler intelligence scale.

    Science.gov (United States)

    Youssef, Doaa Mohammed; Mohamed, Ahmed Hosny; Kamel Attia, Wafaa Mahmoud; Mohammad, Faten Fawzy; El Fatah, Nelly Rafaat Abd; Elshal, Amal Saeed

    2017-06-16

    Many studies described Impaired intelligence, attention, memory and executive function in patients with chronic kidney disease (CKD) dialyzed and non-dialyzed, but there is still lacking the early and sensitive method of detection of these deficits. The purpose of this study is to investigate relation between the brain metabolic alteration [measured by magnetic resonance spectroscopy (MRS)] and cognitive dysfunction in CKD children (detected by psychometric analysis). One hundred and forty patients with CKD were included [ 40 patients with stage 5 CKD on dialysis, 30 patients with stage 4 to 5 CKD without dialysis, and 70 patients with stage 1 to 3 CKD]. All patients with previous neurological disorders were excluded. Conventional MRI, MRS and psychometric assessment by using Wechsler intelligence scale for children third edition was done in all subjects. We found a significant negative correlation between MRS abnormalities and Wechsler IQ Test scores. But there was a significantly positive correlation between the CKD stages and MRS abnormalities in patients with CKD and negative significant correlation between CKD stages and Wechsler IQ test scores in patients with CKD. There were correlations between "the electrolyte disturbance, blood hemoglobin and hypertension" and "the CKD staging, cognitive functions IQ scores and MRS parameter changes". We concluded that both MRS and psychometric tests are sensitive methods for detection of cognitive function affection in CKD children, particularly in dialyzed group and these findings appears before the clinical diagnosis. This article is protected by copyright. All rights reserved.

  3. Measuring illness insight in patients with alcohol-related cognitive dysfunction using the Q8 questionnaire: a validation study

    Science.gov (United States)

    Walvoort, Serge JW; van der Heijden, Paul T; Kessels, Roy PC; Egger, Jos IM

    2016-01-01

    Aim Impaired illness insight may hamper treatment outcome in patients with alcohol-related cognitive deficits. In this study, a short questionnaire for the assessment of illness insight (eg, the Q8) was investigated in patients with Korsakoff’s syndrome (KS) and in alcohol use disorder (AUD) patients with mild neurocognitive deficits. Methods First, reliability coefficients were computed and internal structure was investigated. Then, comparisons were made between patients with KS and patients with AUD. Furthermore, correlations with the Dysexecutive Questionnaire (DEX) were investigated. Finally, Q8 total scores were correlated with neuropsychological tests for processing speed, memory, and executive function. Results Internal consistency of the Q8 was acceptable (ie, Cronbach’s α =0.73). The Q8 items represent one factor, and scores differ significantly between AUD and KS patients. The Q8 total score, related to the DEX discrepancy score and scores on neuropsychological tests as was hypothesized, indicates that a higher degree of illness insight is associated with a higher level of cognitive functioning. Conclusion The Q8 is a short, valid, and easy-to-administer questionnaire to reliably assess illness insight in patients with moderate-to-severe alcohol-related cognitive dysfunction. PMID:27445476

  4. Understanding and Remediating Social-Cognitive Dysfunctions in Patients with Serious Mental Illness Using Relational Frame Theory.

    Science.gov (United States)

    Hendriks, Annemieke L; Barnes-Holmes, Yvonne; McEnteggart, Ciara; De Mey, Hubert R A; Janssen, Gwenny T L; Egger, Jos I M

    2016-01-01

    Impairments in social cognition and perspective-taking play an important role in the psychopathology and social functioning of individuals with social anxiety, autism, or schizophrenia-spectrum disorders, among other clinical presentations. Perspective-taking has mostly been studied using the concept of Theory of Mind (ToM), which describes the sequential development of these skills in young children, as well as clinical populations experiencing perspective-taking difficulties. Several studies mention positive results of ToM based training programs; however, the precise processes involved in the achievement of these improvements are difficult to determine. Relational Frame Theory (RFT) is a modern behavioral account of complex cognitive functions, and is argued to provide a more precise approach to the assessment and training of perspective-taking, among other relational skills. Results of RFT-based studies of perspective-taking in developmental and clinical settings are discussed. The development of training methods targeting perspective-taking deficits from an RFT point of view appears to provide promising applications for the enhancement of current treatments of people with social-cognitive dysfunctions.

  5. Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant

    KAUST Repository

    Hudik, Elodie

    2014-07-18

    The majority of research on cell cycle regulation is focused on the nuclear events that govern the replication and segregation of the genome between the two daughter cells. However, eukaryotic cells contain several compartmentalized organelles with specialized functions, and coordination among these organelles is required for proper cell cycle progression, as evidenced by the isolation of several mutants in which both organelle function and overall plant development were affected. To investigate how chloroplast dysfunction affects the cell cycle, we analyzed the crumpled leaf (crl) mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for a chloroplastic protein and displays particularly severe developmental defects. In the crl mutant, we reveal that cell cycle regulation is altered drastically and that meristematic cells prematurely enter differentiation, leading to reduced plant stature and early endoreduplication in the leaves. This response is due to the repression of several key cell cycle regulators as well as constitutive activation of stress-response genes, among them the cell cycle inhibitor SIAMESE-RELATED5. One unique feature of the crl mutant is that it produces aplastidic cells in several organs, including the root tip. By investigating the consequence of the absence of plastids on cell cycle progression, we showed that nuclear DNA replication occurs in aplastidic cells in the root tip, which opens future research prospects regarding the dialogue between plastids and the nucleus during cell cycle regulation in higher plants.

  6. Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Benjamin Wiench

    2012-01-01

    Full Text Available Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin, a natural naphthoquinone, was used in traditional Chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer activities of shikonin. We found that shikonin has strong cytotoxic effects on 15 cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide mRNA expression studies showed that shikonin induced genetic pathways regulating cell cycle, mitochondrial function, levels of reactive oxygen species, and cytoskeletal formation. Taking advantage of the inherent fluorescence of shikonin, we analyzed its uptake and distribution in live cells with high spatial and temporal resolution using flow cytometry and confocal microscopy. Shikonin was specifically accumulated in the mitochondria, and this accumulation was associated with a shikonin-dependent deregulation of cellular Ca2+ and ROS levels. This deregulation led to a breakdown of the mitochondrial membrane potential, dysfunction of microtubules, cell-cycle arrest, and ultimately induction of apoptosis. Seeing as both the metabolism and the structure of mitochondria show marked differences between cancer cells and normal cells, shikonin is a promising candidate for the next generation of chemotherapy.

  7. Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Makoto Akashi

    2017-06-01

    Full Text Available Hypercholesterolemia is a well-known risk factor for a wide range of diseases in developed countries. Here, we report that mice lacking functional LDLR (low density lipoprotein receptor, an animal model of human familial hypercholesterolemia, show circadian abnormalities. In free running behavioral experiments in constant darkness, these mice showed a prolonged active phase and distinctly bimodal rhythms. Even when the circadian rhythms were entrained by light and dark cycles, these mice showed a significant attenuation of behavioral onset intensity at the start of the dark period. Further, we hypothesized that the combination of hypercholesterolemia and circadian abnormalities may affect cardiovascular disease progression. To examine this possibility, we generated LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing a mutation into Period2, a core clock gene, and found that these mice showed a significant enlargement of artery plaque area with an increase in inflammatory cytokine IL-6 levels. These results suggest that circadian dysfunction may be associated with the development or progression of cardiovascular diseases.

  8. Multi-organic dysfunction syndrome caused by dengue 3 in children of Neiva Huila, Colombia

    International Nuclear Information System (INIS)

    Salgado, Doris; Vega, Martha R; Panqueva, Cesar A

    2006-01-01

    Dengue is the main arthropod -transmitted viral disease in the world with a growing number of cases in Neiva, Colombia. Clinical presentation of dengue hemorrhagic fever (DHF) is showing compromise of organs different from endothelium which could be associated to the circulating serotype and/or host immunological factors. Objective. To alert about the association of multiple organic dysfunction (MOD) and DHF. Results. MOD associated to DHF is described in three girls with an average of 16 months of age, two 7-month sold and 1 three year old. The evolution of fever at the beginning was 4 days; they had shock resistant to usual treatment with crystalloid and colloids with tachycardia,ventricular arrhythmia, increased CPK MB, AST and ALT,coagulopathy with prolonged PTT and PT but without severe thrombocytopenia, metabolic alteration with acidaemia and hypoglycemia in the three girls. Score for MOD was applied with an average of 23 and evidence of myocardial, hepatic and hematological major compromise. dengue 3 was showed by RT-PCR. Discussion. Similar reports are compared with these cases and probable pathophysiologic mechanisms are discussed. Conclusion. It has to be stressed that DHF might affect different organs, because of this definition of severity in dengue has to be reconsidered. An early thinking in different organs affected might help to introduce an opportune intervention or treatment.

  9. Microglial inhibitory mechanism of Coenzyme Q10 against Aβ (1-42 induced cognitive dysfunctions: possible behavioral, biochemical, cellular and histopathological alterations

    Directory of Open Access Journals (Sweden)

    Arti eSingh

    2015-11-01

    Full Text Available Rationale: Alzheimer’s disease (AD is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ (1-42 is a reliable model of AD that recapitulates many aspects of human AD. Objective: The present study has been designed to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10 and its modulation with minocycline (microglial inhibitor against Aβ (1-42 induced cognitive dysfunction in rats. Method: Intrahippocampal (i.h. Aβ (1-42 (1µg/µl; 4µl/site were administered followed by drug treatment with galantamine (2 mg/kg, CoQ10 (20 and 40 mg/kg, minocycline (50 and 100 mg/kg and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE level, proinflammatory markers (TNF-α, mitochondrial respiratory enzyme complexes (I-IV and histopathological examinations were assessed.Results: Aβ (1-42 administration significantly impaired cognitive performance in Morris water maze (MWM performance test, causes oxidative stress, raised AChE level, caused neuroinflammation, mitochondrial dysfunction and histopathological alterations as compared to sham treatment. Treatment with CoQ10 (20 and 40 mg/kg and minocycline (50 and 100 mg/kg alone for 21days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ, reduced AChE activity, oxidative damage (reduced LPO, nitrite level and restored SOD, catalase and GHS levels, TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV activities and histopathological alterations as compared to control (Aβ (1-42 treated animals group. Further, combination of minocycline (50 and 100 mg/kg with CoQ10 (20 and 40 mg/kg significantly modulate the protective effect of CoQ10 as compared to their effect alone. Conclusion: The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia inhibitory

  10. Cognitive dysfunction in bipolar disorder and schizophrenia: a systematic review of meta-analyses

    Directory of Open Access Journals (Sweden)

    Bortolato B

    2015-12-01

    Full Text Available Beatrice Bortolato,1 Kamilla W Miskowiak,2 Cristiano A Köhler,3 Eduard Vieta,4 André F Carvalho3 1Department of Mental Health, ULSS 10 “Veneto Orientale”, Venice, Italy; 2Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 3Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; 4Bipolar Disorders Program, Institute of Neuroscience, Hospital Clínic Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Catalonia, Spain Abstract: Cognitive impairment is a core feature of schizophrenia (SZ and bipolar disorder (BD. A neurocognitive profile characterized by widespread cognitive deficits across multiple domains in the context of substantial intellectual impairment, which appears to antedate illness onset, is a replicated finding in SZ. There is no specific neuropsychological signature that can facilitate the diagnostic differentiation of SZ and BD, notwithstanding, neuropsychological deficits appear more severe in SZ. The literature in this field has provided contradictory results due to methodological differences across studies. Meta-analytic techniques may offer an opportunity to synthesize findings and to control for potential sources of heterogeneity. Here, we performed a systematic review of meta-analyses of neuropsychological findings in SZ and BD. While there is no conclusive evidence for progressive cognitive deterioration in either SZ or BD, some findings point to more severe cognitive deficits in patients with early illness onset across both disorders. A compromised pattern of cognitive functioning in individuals at familiar and/or clinical risk to psychosis as well as in first-degree relatives of BD patients suggests that early neurodevelopmental factors may play a role in the emergence of cognitive deficits in both disorders. Premorbid intellectual impairment in SZ and at least in a

  11. Maternal exposure to airborne particulate matter causes postnatal immunological dysfunction in mice offspring

    International Nuclear Information System (INIS)

    Hong, Xinru; Liu, Chaobin; Chen, Xiaoqiu; Song, Yanfeng; Wang, Qin; Wang, Ping; Hu, Dian

    2013-01-01

    Evidence suggests that prenatal exposure to air pollution affects the ontogeny and development of the fetal immune system. The aim of this study was to investigate the effect of maternal exposure to airborne particulate matter (PM) on immune function in postnatal offspring. Pregnant female ICR mice were intralaryngopharyngeally administered with 30 μl of phosphate buffered solution (the control group) or resuspended PM of Standard Reference Material 1649a at 0.09 (low), 0.28 (medium), 1.85 (high) or 6.92 (overdose) μg/μl once every three days from day 0 to 18 of pregnancy (n = 8–10). Offspring were sacrificed on postnatal day 30. Interleukin-4 and interferon-γ levels in plasma and splenocytes, splenic lymphocyte proliferation, and expressions of GATA-3 and T-bet mRNA in the spleen were tested. The spleen and thymus were histopathologically examined. The offspring of the medium, high and overdose PM-exposed dams showed significantly suppressed splenocyte proliferation. Decreased interferon-γ and increased interleukin-4 levels in the blood and splenocytes, and lowered T-bet and elevated GATA-3 mRNA expressions were found in the spleen in the medium, high and overdose groups when compared with the control or low dose group (P < 0.05). Histopathology revealed prominent tissue damage in the spleen and thymus in the overdose group. These results suggest that exposure of pregnant mice to PM modulates the fetal immune system, resulting in postnatal immune dysfunction by exacerbation of Thl/Th2 deviation. This deviation is associated with altered T-bet and GATA-3 gene expressions

  12. Penile artery shunt syndrome: a novel cause of erectile dysfunction after penile revascularization surgery.

    Science.gov (United States)

    Pavlinec, Jonathan G; Hakky, Tariq S; Yang, Christopher; Massis, Kamal; Munarriz, Ricardo; Carrion, Rafael E

    2014-09-01

    Penile revascularization is a surgical treatment option for erectile dysfunction (ED) in healthy individuals due to a focal arterial occlusion in the absence of generalized vascular disease. Most described failures have been attributed to graft stenosis or disruption of the anastomosis. We report a novel phenomenon called Penile Artery Shunt Syndrome that contributed to persistent ED in a patient after penile microvascular arterial bypass surgery. A 26-year-old man presented for evaluation of long-standing ED, which was attributed to trauma sustained 12 years earlier. He had difficulty obtaining and maintaining erections despite oral pharmacotherapy. Clinical data related to the case were studied, analyzed, and reviewed with urologic and radiologic specialists at multiple centers that collaborated in the care of this patient. Penile duplex ultrasound peak systolic velocities and five-item International Index for Erectile Function questionnaire scores were the main outcome measures. Initial diagnostic workup of the patient confirmed severe insufficiency of the left cavernosal artery, with no evidence of venous leak. The patient underwent penile microvascular arterial bypass surgery with anastomosis of the left inferior epigastric artery to the left dorsal penile artery. The patient had persistence of severe ED despite patent anastomosis by penile duplex ultrasound. Subsequent arteriography revealed an arterial shunt due to an aberrant obturator artery arising from the donor inferior epigastric artery. The patient underwent embolization of the aberrant obturator artery, with resolution of the shunt and marked improvement in erectile function. The presence of an aberrant obturator artery arising from the inferior epigastric artery may predispose to persistent ED after revascularization due to the creation of a shunt phenomenon. Pelvic arteriography may be useful in identifying anomalous anatomic considerations prior to penile revascularization and to evaluate patients

  13. Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

    Science.gov (United States)

    Daulatzai, Mak Adam

    2016-10-01

    Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

  14. Cognitive dysfunction in urban elderly people: an exploratory study using neuropsychological and neuroimaging perspective

    Directory of Open Access Journals (Sweden)

    Sreerupa Ghose

    2017-06-01

    Full Text Available Background: Cognitive impairment is an integral part of old age as well as it is a part of many neurodegenerative disorders. Early identification of cognitive impairment is necessary in order to make treatment and rehabilitation possible. Materials and methods: Keeping in mind that early identification of cognitive impairment is necessary, a sample of 20 elderly patients with memory complaints who were referred for magnetic resonance imaging (MRI with symptoms of peripheral nervous system disorder by neurologists have been assessed using neuropsychological tests and MRI, and results have been analysed using IBM SPSS 21 and DICOM software. Results: Neuropsychological test findings suggest that age, sex, and education are related to performance of the participants on different tests of cognitive functions in different ways. Scores on the tests of delayed memory and verbal fluency emerged as positive predictors of activity level. On the basis of MRI, the elderly people were identified with periventricular hyper-intensity of white matter and global cortical atrophy. A comparison of the two groups (on the basis of MRI findings suggest that elderly people with global cortical atrophy were found to be significantly more impaired on visuospatial tasks in comparison to the group with periventricular hyper-intensity of white matter, among other tests of cognitive functions. Conclusion: In spite of the absence of manifestation of dementing illness at clinical level, the participants actually exhibited underlying pathological process which can be detected with neuropsychological testing in conjunction with neuroimaging.

  15. Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

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    Ryuji Sakakibara

    2011-01-01

    Full Text Available Bladder dysfunction (urinary urgency/frequency, bowel dysfunction (constipation, and sexual dysfunction (erectile dysfunction (also called “pelvic organ” dysfunctions are common nonmotor disorders in Parkinson's disease (PD. In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

  16. Bladder, bowel, and sexual dysfunction in Parkinson's disease.

    Science.gov (United States)

    Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

    2011-01-01

    Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

  17. Social cognition dysfunctions in patients with epilepsy: Evidence from patients with temporal lobe and idiopathic generalized epilepsies.

    Science.gov (United States)

    Realmuto, Sabrina; Zummo, Leila; Cerami, Chiara; Agrò, Luigi; Dodich, Alessandra; Canessa, Nicola; Zizzo, Andrea; Fierro, Brigida; Daniele, Ornella

    2015-06-01

    Despite an extensive literature on cognitive impairments in focal and generalized epilepsy, only a few number of studies specifically explored social cognition disorders in epilepsy syndromes. The aim of our study was to investigate social cognition abilities in patients with temporal lobe epilepsy (TLE) and in patients with idiopathic generalized epilepsy (IGE). Thirty-nine patients (21 patients with TLE and 18 patients with IGE) and 21 matched healthy controls (HCs) were recruited. All subjects underwent a basic neuropsychological battery plus two experimental tasks evaluating emotion recognition from facial expression (Ekman-60-Faces test, Ek-60F) and mental state attribution (Story-based Empathy Task, SET). In particular, the latter is a newly developed task that assesses the ability to infer others' intentions (i.e., intention attribution - IA) and emotions (i.e., emotion attribution - EA) compared with a control condition of physical causality (i.e., causal inferences - CI). Compared with HCs, patients with TLE showed significantly lower performances on both social cognition tasks. In particular, all SET subconditions as well as the recognition of negative emotions were significantly impaired in patients with TLE vs. HCs. On the contrary, patients with IGE showed impairments on anger recognition only without any deficit at the SET task. Emotion recognition deficits occur in patients with epilepsy, possibly because of a global disruption of a pathway involving frontal, temporal, and limbic regions. Impairments of mental state attribution specifically characterize the neuropsychological profile of patients with TLE in the context of the in-depth temporal dysfunction typical of such patients. Impairments of socioemotional processing have to be considered as part of the neuropsychological assessment in both TLE and IGE in view of a correct management and for future therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Dysfunctions of decision-making and cognitive control as transdiagnostic mechanisms of mental disorders: advances, gaps, and needs in current research.

    Science.gov (United States)

    Goschke, Thomas

    2014-01-01

    Disadvantageous decision-making and impaired volitional control over actions, thoughts, and emotions are characteristics of a wide range of mental disorders such as addiction, eating disorders, depression, and anxiety disorders and may reflect transdiagnostic core mechanisms and possibly vulnerability factors. Elucidating the underlying neurocognitive mechanisms is a precondition for moving from symptom-based to mechanism-based disorder classifications and ultimately mechanism-targeted interventions. However, despite substantial advances in basic research on decision-making and cognitive control, there are still profound gaps in our current understanding of dysfunctions of these processes in mental disorders. Central unresolved questions are: (i) to which degree such dysfunctions reflect transdiagnostic mechanisms or disorder-specific patterns of impairment; (ii) how phenotypical features of mental disorders relate to dysfunctional control parameter settings and aberrant interactions between large-scale brain systems involved in habit and reward-based learning, performance monitoring, emotion regulation, and cognitive control; (iii) whether cognitive control impairments are consequences or antecedent vulnerability factors of mental disorders; (iv) whether they reflect generalized competence impairments or context-specific performance failures; (v) whether not only impaired but also chronic over-control contributes to mental disorders. In the light of these gaps, needs for future research are: (i) an increased focus on basic cognitive-affective mechanisms underlying decision and control dysfunctions across disorders; (ii) longitudinal-prospective studies systematically incorporating theory-driven behavioural tasks and neuroimaging protocols to assess decision-making and control dysfunctions and aberrant interactions between underlying large-scale brain systems; (iii) use of latent-variable models of cognitive control rather than single tasks; (iv) increased focus on

  19. Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study.

    Science.gov (United States)

    Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

    2016-05-01

    Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~30dB(A); urban noise: building site noise, 68-78dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68-78dB(A)], 7-14days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

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    Jennifer E Bruin

    Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.

  1. Cognitive Dysfunction Is Worse among Pediatric Patients with Bipolar Disorder Type I than Type II

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    Schenkel, Lindsay S.; West, Amy E.; Jacobs, Rachel; Sweeney, John A.; Pavuluri, Mani N.

    2012-01-01

    Background: Impaired profiles of neurocognitive function have been consistently demonstrated among pediatric patients with bipolar disorder (BD), and may aid in the identification of endophenotypes across subtypes of the disorder. This study aims to determine phenotypic cognitive profiles of patients with BD Type I and II. Methods: Subjects (N =…

  2. Selective Attention, Working Memory, and Executive Function as Potential Independent Sources of Cognitive Dysfunction in Schizophrenia.

    Science.gov (United States)

    Gold, James M; Robinson, Benjamin; Leonard, Carly J; Hahn, Britta; Chen, Shuo; McMahon, Robert P; Luck, Steven J

    2017-11-11

    People with schizophrenia demonstrate impairments in selective attention, working memory, and executive function. Given the overlap in these constructs, it is unclear if these represent distinct impairments or different manifestations of one higher-order impairment. To examine this question, we administered tasks from the basic cognitive neuroscience literature to measure visual selective attention, working memory capacity, and executive function in 126 people with schizophrenia and 122 healthy volunteers. Patients demonstrated deficits on all tasks with the exception of selective attention guided by strong bottom-up inputs. Although the measures of top-down control of selective attention, working memory, and executive function were all intercorrelated, several sources of evidence indicate that working memory and executive function are separate sources of variance. Specifically, both working memory and executive function independently contributed to the discrimination of group status and independently accounted for variance in overall general cognitive ability as assessed by the MATRICS battery. These two cognitive functions appear to be separable features of the cognitive impairments observed in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Do patients with OCD and pathological gambling have similar dysfunctional cognitions

    NARCIS (Netherlands)

    Anholt, G.E.; Emmelkamp, P.M.G.; Cath, D.C.; van Oppen, P.; Nelissen, H.; Smit, J.H.

    2004-01-01

    The obsessive-compulsive spectrum disorder (OCSD) theory postulates that a wide range of disorders is closely related to OCD. Current cognitive models ascertain that certain beliefs leading to misinterpretation of the significance of intrusions are important in the etiology and maintenance of OCD.

  4. Dysfunctional breathing and reaching one’s physiological limit as causes of exercise-induced dyspnoea

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    Julie Depiazzi

    2016-06-01

    This review provides an overview of the spectrum of conditions that can present as exercise-­induced breathlessness experienced by young subjects participating in sport and aims to promote understanding of the need for accurate assessment of an individual’s symptoms. We will highlight the high incidence of nonasthmatic causes, which simply require reassurance or simple interventions from respiratory physiotherapists or speech pathologists.

  5. Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection.

    Science.gov (United States)

    Kumar, Ajay; Deep, Amar; Gupta, Rakesh K; Atam, Virendra; Mohindra, Samir

    2017-09-01

    This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient ( n  = 40), and healthy controls ( n  = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t -test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

  6. Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction.

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    Tokunaga, Shinji; Araki, Toshiyuki

    2012-03-01

    Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wld(S) Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wld(S) mice are protected from, we exposed primary cultured neurons derived from wld(S) mice to various components of hypoxic stress. We found that wld(S) mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wld(S) mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that Wld(S) protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. Copyright © 2011 Wiley Periodicals, Inc.

  7. MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves’ Disease

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    Yicheng Qi

    2017-11-01

    Full Text Available ContextAberrant CD4+ T cell function plays a critical role in the process of Graves’ disease (GD. MicroRNAs (miRNAs are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear.ObjectiveTo investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients.MethodsWe compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD patients with those from healthy controls. The most significantly dysregulated miRNAs were selected and their correlations with clinical parameters were analyzed. The effect of miR-4443 on CD4+ T cells cytokines production and proliferation was assessed. The potential gene target was identified and validated.ResultsGD patients had unique pattern of miRNA expression profile in CD4+ T cells comparing to healthy subjects. miR-10a, miR-125b, and miR-4443 were the three most significantly dysregulated miRNAs. The elevated miR-4443 levels were strongly correlated with clinical parameters in an independent dataset of UGD patients (N = 40, while miR-4443 was normally expressed in GD patients with euthyroidism and negative TRAb level. We found that miR-4443 directly inhibited TNFR-associated factor (TRAF 4 expression to increase CD4+ T cells cytokines secretion as well as proliferation through the NF-κB pathway. Furthermore, the TRAF4 levels in GD patients were inversely correlated with miR-4443, and knocking down TRAF4 had a similar effect with miR-4443 overexpression.ConclusionThe increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.

  8. Magnitude of cognitive dysfunction in adults with type 2 diabetes: a meta-analysis of six cognitive domains and the most frequently reported neuropsychological tests within domains.

    Science.gov (United States)

    Palta, Priya; Schneider, Andrea L C; Biessels, Geert Jan; Touradji, Pegah; Hill-Briggs, Felicia

    2014-03-01

    The objectives were to conduct a meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards to determine effect sizes (Cohen's d) for cognitive dysfunction in adults with type 2 diabetes, relative to nondiabetic controls, and to obtain effect sizes for the most commonly reported neuropsychological tests within domains. Twenty-four studies, totaling 26,137 patients (n = 3351 with diabetes), met study inclusion criteria. Small to moderate effect sizes were obtained for five of six domains: motor function (3 studies, n = 2374; d = -0.36), executive function (12 studies, n = 1784; d = -0.33), processing speed (16 studies, n = 3076; d = -0.33), verbal memory (15 studies, n = 4,608; d = -0.28), and visual memory (6 studies, n = 1754; d = -0.26). Effect size was smallest for attention/concentration (14 studies, n = 23,143; d = -0.19). The following tests demonstrated the most notable performance decrements in diabetes samples: Grooved Pegboard (dominant hand) (d = -0.60), Rey Auditory Verbal Learning Test (immediate) (d = -0.40), Trails B (d = -0.39), Rey-Osterreith Complex Figure (delayed) (d = -0.38), Trails A (d = -0.34), and Stroop Part I (d = -0.28). This study provides effect sizes to power future epidemiological and clinical diabetes research studies examining cognitive function and to help inform the selection of neuropsychological tests.

  9. Classic conditioning and dysfunctional cognitions in patients with panic disorder and agoraphobia treated with an implantable cardioverter/defibrillator.

    Science.gov (United States)

    Godemann, F; Ahrens, B; Behrens, S; Berthold, R; Gandor, C; Lampe, F; Linden, M

    2001-01-01

    A model for the development of anxiety disorders (panic disorder with or without agoraphobia) is needed. Patients with an implantable cardioverter/defibrillator (ICD) are exposed to repeated electric shocks. If the theory of anxiety development by aversive classic conditioning processes is valid, these repeated shocks should lead to an increased risk of anxiety disorders. To study this hypothesis, we retrospectively studied 72 patients after implantation of an automatic ICD. Patients were assessed with the semistructured Diagnostic Interview of Psychiatric Disease 1 to 6 years after implantation of an automatic ICD. Panic disorder and/or agoraphobia was diagnosed in patients who fulfilled all DSM-III-R criteria for those conditions. Anxiety disorder developed in 15.9% of patients after ICD implantation. This was significantly related to the frequency of repeated defibrillation (shocks) to stop malignant ventricular arrhythmias. Dysfunctional cognitions are an additional vulnerability factor. The data support both the conditioning hypothesis and the cognitive model of anxiety development. These findings suggest that ICD patients are an appropriate risk population for a prospective study of the development of anxiety disorders.

  10. Effectiveness of a Cognitive Behavioral Therapy for Dysfunctional Eating among Patients Admitted for Bariatric Surgery: A Randomized Controlled Trial

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    Hege Gade

    2014-01-01

    Full Text Available Objective. To examine whether cognitive behavioral therapy (CBT alleviates dysfunctional eating (DE patterns and symptoms of anxiety and depression in morbidly obese patients planned for bariatric surgery. Design and Methods. A total of 98 (68 females patients with a mean (SD age of 43 (10 years and BMI 43.5 (4.9 kg/m2 were randomly assigned to a CBT-group or a control group receiving usual care (i.e., nutritional support and education. The CBT-group received ten weekly intervention sessions. DE, anxiety, and depression were assessed by the TFEQ R-21 and HADS, respectively. Results. Compared with controls, the CBT-patients showed significantly less DE, affective symptoms, and a larger weight loss at follow-up. The effect sizes were large (DE-cognitive restraint, g=-.92, P≤.001; DE-uncontrolled eating, g=-.90, P≤.001, moderate (HADS-depression, g=-.73, P≤.001; DE-emotional eating, g=-.67, P≤.001; HADS-anxiety, g=-.62, P=.003, and low (BMI, g=-.24, P=.004. Conclusion. This study supports the use of CBT in helping patients preparing for bariatric surgery to reduce DE and to improve mental health. This clinical trial is registered with NCT01403558.

  11. Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury.

    Science.gov (United States)

    Newell, Elizabeth A; Todd, Brittany P; Mahoney, Jolonda; Pieper, Andrew A; Ferguson, Polly J; Bassuk, Alexander G

    2018-01-01

    Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion-mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling.

  12. Cognitive dysfunction in the dystrophin-deficient mouse model of Duchenne muscular dystrophy: A reappraisal from sensory to executive processes.

    Science.gov (United States)

    Chaussenot, Rémi; Edeline, Jean-Marc; Le Bec, Benoit; El Massioui, Nicole; Laroche, Serge; Vaillend, Cyrille

    2015-10-01

    Duchenne muscular dystrophy (DMD) is associated with language disabilities and deficits in learning and memory, leading to intellectual disability in a patient subpopulation. Recent studies suggest the presence of broader deficits affecting information processing, short-term memory and executive functions. While the absence of the full-length dystrophin (Dp427) is a common feature in all patients, variable mutation profiles may additionally alter distinct dystrophin-gene products encoded by separate promoters. However, the nature of the cognitive dysfunctions specifically associated with the loss of distinct brain dystrophins is unclear. Here we show that the loss of the full-length brain dystrophin in mdx mice does not modify the perception and sensorimotor gating of auditory inputs, as assessed using auditory brainstem recordings and prepulse inhibition of startle reflex. In contrast, both acquisition and long-term retention of cued and trace fear memories were impaired in mdx mice, suggesting alteration in a functional circuit including the amygdala. Spatial learning in the water maze revealed reduced path efficiency, suggesting qualitative alteration in mdx mice learning strategy. However, spatial working memory performance and cognitive flexibility challenged in various behavioral paradigms in water and radial-arm mazes were unimpaired. The full-length brain dystrophin therefore appears to play a role during acquisition of associative learning as well as in general processes involved in memory consolidation, but no overt involvement in working memory and/or executive functions could be demonstrated in spatial learning tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Hippocampal Dysfunction Provoked by Mercury Chloride Exposure: Evaluation of Cognitive Impairment, Oxidative Stress, Tissue Injury and Nature of Cell Death

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    Walessa Alana Bragança Aragão

    2018-01-01

    Full Text Available Mercury (Hg is a highly toxic metal, which can be found in its inorganic form in the environment. This form presents lower liposolubility and lower absorption in the body. In order to elucidate the possible toxicity of inorganic Hg in the hippocampus, we investigated the potential of low doses of mercury chloride (HgCl2 to promote hippocampal dysfunction by employing a chronic exposure model. For this, 56 rats were exposed to HgCl2 (0.375 mg/kg/day via the oral route for 45 days. After the exposure period, the animals were submitted to the cognitive test of fear memory. The hippocampus was collected for the measurement of total Hg levels, analysis of oxidative stress, and evaluation of cytotoxicity, apoptosis, and tissue injury. It was observed that chronic exposure to inorganic Hg promotes an increase in mercury levels in this region and damage to short- and long-term memory. Furthermore, we found that this exposure model provoked oxidative stress, which led to cytotoxicity and cell death by apoptosis, affecting astrocytes and neurons in the hippocampus. Our study demonstrated that inorganic Hg, even with its low liposolubility, is able to produce deleterious effects in the central nervous system, resulting in cognitive impairment and hippocampal damage when administered for a long time at low doses in rats.

  14. Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia.

    Science.gov (United States)

    Roberts, Rosebud O; Christianson, Teresa J H; Kremers, Walter K; Mielke, Michelle M; Machulda, Mary M; Vassilaki, Maria; Alhurani, Rabe E; Geda, Yonas E; Knopman, David S; Petersen, Ronald C

    2016-01-01

    To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia. Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI [aMCI] and nonamnestic MCI [naMCI]), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures. Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4% were men, the mean duration of education was 14.3 years, and 25.4% were APOE ε4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles

  15. Chronopathological aspects of sleep disorders and cognitive dysfunctions in children with visual impairments

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    I. A. Kelmanson

    2015-01-01

    Full Text Available The most important and noticeable rhythmical phenomenon observed in the human body is a sleep-wake rhythm and related physical and mental changes. The so-called circadian rhythms that vary over a period of approximately 24 hours are most important. The suprachi-asmatic nucleus of the hypothalamus is a primary circadian pacemaker in mammals; and light pulses out of all stimuli obtained by this structure have been mostly studied. The light pulses unrelated to visual perception serve as the most important synchronizers of circadian rhythms. Children with visual impairments lack adequate photic stimulation and hence circadian rhythm disorders develop and cognitive impairments worsen with a high probability. The most important types of sleep disorders in children with visual impairments are considered; their negative impact on a child's cognitive functions is discussed; possible correction approaches are laid down.

  16. Relationship between glutamate dysfunction and symptoms and cognitive function in psychosis

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    Kate eMerritt

    2013-11-01

    Full Text Available The glutamate hypothesis of schizophrenia, proposed over two decades ago, originated following the observation that administration of drugs that block NMDA glutamate receptors, such as ketamine, could induce schizophrenia–like symptoms. Since then, this hypothesis has been extended to describe how glutamate abnormalities may disturb brain function and underpin psychotic symptoms and cognitive impairments. The glutamatergic system is now a major focus for the development of new compounds in schizophrenia. Relationships between regional brain glutamate function and symptom severity can be investigated using proton magnetic resonance spectroscopy (1H-MRS to estimate levels of glutamatergic metabolites in vivo. Here we briefly review the 1H-MRS studies that have explored relationships between glutamatergic metabolites, symptoms and cognitive function in clinical samples. While some of these studies suggest that more severe symptoms may be associated with elevated glutamatergic function in the anterior cingulate, studies in larger patient samples selected on the basis of symptom severity are required.

  17. A cognitive neuroscience perspective on psychopathy: Evidence for paralimbic system dysfunction

    OpenAIRE

    Kiehl, Kent A.

    2006-01-01

    Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes as...

  18. The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction.

    Science.gov (United States)

    Thompson, Hannah E; Almaghyuli, Azizah; Noonan, Krist A; Barak, Ohr; Lambon Ralph, Matthew A; Jefferies, Elizabeth

    2018-01-03

    Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., , Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal 'hub' in combination with modality-specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time- and task-appropriate behaviour. Executive-semantic goal representations, largely supported by executive regions such as frontal and parietal cortex, are thought to allow the generation of non-dominant aspects of knowledge when these are appropriate for the task or context. Semantic aphasia (SA) patients have executive-semantic deficits, and these are correlated with general executive impairment. If the CSC proposal is correct, patients with executive impairment should not only exhibit impaired semantic cognition, but should also show characteristics that align with those observed in SA. This possibility remains largely untested, as patients selected on the basis that they show executive impairment (i.e., with 'dysexecutive syndrome') have not been extensively tested on tasks tapping semantic control and have not been previously compared with SA cases. We explored conceptual processing in 12 patients showing symptoms consistent with dysexecutive syndrome (DYS) and 24 SA patients, using a range of multimodal semantic assessments which manipulated control demands. Patients with executive impairments, despite not being selected to show semantic impairments, nevertheless showed parallel patterns to SA cases. They showed strong effects of distractor strength, cues and miscues, and probe-target distance, plus minimal effects of word frequency on comprehension (unlike semantic dementia patients with degradation of conceptual knowledge). This supports a component process account of semantic cognition in which retrieval is shaped by control processes, and confirms that deficits in SA patients reflect

  19. Tangzhining exhibits a protective effect against cognitive dysfunction in diabetic rats

    OpenAIRE

    Song, Xiaomei; Wang, Wei; Kang, Yaguo; Zhang, Xin; Jiang, Yi; Yue, Zhenggang; Tang, Zhishu

    2015-01-01

    Previous studies have suggested that diabetes significantly impairs the cognitive function. Tangzhining (TZN), as a kind of Traditional Chinese Medicine (TCM), has been widely used to treat diabetes in China. However, the effect of TZN on treatment of diabetes-induced learning and memory deficits has not been well documented. The present study was to investigate the effect of TZN on diabetes-induced learning and memory deficits and delineate the underlying molecular mechanism. Diabetic rats w...

  20. Relationship between Glutamate Dysfunction and Symptoms and Cognitive Function in Psychosis

    OpenAIRE

    Merritt, Kate; McGuire, Philip; Egerton, Alice

    2013-01-01

    The glutamate hypothesis of schizophrenia, proposed over two decades ago, originated following the observation that administration of drugs that block NMDA glutamate receptors, such as ketamine, could induce schizophrenia-like symptoms. Since then, this hypothesis has been extended to describe how glutamate abnormalities may disturb brain function and underpin psychotic symptoms and cognitive impairments. The glutamatergic system is now a major focus for the development of new compounds in sc...

  1. Glucose impairment and ghrelin gene variants are associated to cognitive dysfunction.

    Science.gov (United States)

    Mora, M; Mansego, M L; Serra-Prat, M; Palomera, E; Boquet, X; Chaves, J F; Puig-Domingo, M

    2014-04-01

    Cognitive state and brain volume have been related to body mass index, abdominal fat, waist-hip ratio, components of metabolic syndrome (MS) and ghrelin. Genetic variations within the ghrelin gene have been recently associated to MS. The aim of our study was to investigate cognitive state by Mini-Mental State Examination (MMSE) in relation to MS components (ATP-III criteria) and ghrelin gene polymorphisms in dwelling individuals aged ≥70. 280 subjects (137 men/143 women, age 77.03 ± 5.92) from the Mataró Ageing Study were included. Individuals were phenotypically characterized by anthropometric variables, lipids, glucose, blood pressure and MMSE. SNPs -501AC (rs26802), -994CT (rs26312), -604GA (rs27647), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene were studied. Genotypes were determined by polymerase chain reaction and SNapshot minisequencing. 22.1 % had MMSE Ghrelin SNPs were associated to MMSE: M72L C/A genotype showed lower score than C/C (p = 0.032, after adjusting for confounders 0.049); L90G A/T genotype showed lower score than A/A (p = 0.054, after adjusting 0.005). MMSE Ghrelin gene variant influence cognitive function in old dwelling individuals participating in the Mataró Ageing Study.

  2. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

    Science.gov (United States)

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-05-14

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

  3. Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

    Science.gov (United States)

    Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

    2012-03-01

    Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

  4. Erectile Dysfunction

    Science.gov (United States)

    ... or other heart problems take medications that contain nitrates to help the blood flow better to the ... erectile dysfunction can affect the way that the nitrates work—and cause blood pressure to drop to ...

  5. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  6. Improvement in subclinical cognitive dysfunction with thyroxine therapy in hypothyroidism: A study from tertiary care center

    Directory of Open Access Journals (Sweden)

    Sridevi Paladugu

    2015-01-01

    Full Text Available Aim: To evaluate the effect of hypothyroidism (both overt and subclinical on cognitive function using latencies of P300 auditory evoked potentials (AEPs. P300 latency suggests that shorter latency times are related to better cognitive performance. P300 latencies were also done after thyroxine replacement to see the effect of treatment on cognitive function. Materials and Methods: Biochemically proven new onset cases with hypothyroidism (overt and subclinical were enrolled into the study, AEPs of these two groups when compared with matched controls. After detailed history and physical examination, P300 potentials were recorded at two points Cz and Pz (Cz: On the midline of the head at the vertex, Pz: On the midline of the head between the vertex and occipital protuberance using a Nicolet Viking Select neuro diagnostic system version 10.0. The study was done in electrophysiology lab in Osmania Medical College. Results: A patient characteristics of both cases and controls were comparable. The cases consisted of two groups, overt hypothyroid cases 24, mean thyroid stimulating hormone (TSH values in them was 94, subclinical cases 21 in whom mean TSH value was 12.3. Mean P300 latencies of all cases at Cz was 342.42 ± 29.5 ms, and at Pz was 345.4 ± 30 ms. Mean P300 latencies of controls at Cz was 296.4 ± 34 ms and at Pz was 297.9 ± 33 ms (difference in P < 0.001. Mean P300 values in overt cases were 362.6 ± 32.9 ms at Cz, and at Pz it was 362.5 ± 33.9 ms. Mean P300 values in subclinical cases were 319.3 ± 30.9 ms at Cz, and at Pz it was 316.4 ± 27.9 ms. P300 values in overt cases were highly significant as compared to controls, and P300 values in the subclinical cases versus controls were also significant (P < 0.001. Conclusion: P300 latency prolongation in both clinical and subclinical hypothyroid cases shows that cognitive function is affected adversely in hypothyroidism including the subclinical hypothyroid cases. Larger studies evaluating

  7. Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined 'Timed Up and Go' Test (iTUG).

    Science.gov (United States)

    Geiger, Maxime; Bonnyaud, Céline; Fery, Yves-André; Bussel, Bernard; Roche, Nicolas

    2017-01-01

    Motor imagery (MI) capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known. To assess temporal congruence between the Timed Up and Go test (TUG) and the imagined TUG (iTUG) tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence. TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA), the Frontal Assessment Battery at Bedside (FAB) and the Bells Test. The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02). Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013), likely suggesting that impairment of attention was a contributing factor. These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction.

  8. A pilot study to determine the feasibility of enhancing cognitive abilities in children with sensory processing dysfunction.

    Directory of Open Access Journals (Sweden)

    Joaquin A Anguera

    Full Text Available Children with Sensory Processing Dysfunction (SPD experience incoming information in atypical, distracting ways. Qualitative challenges with attention have been reported in these children, but such difficulties have not been quantified using either behavioral or functional neuroimaging methods. Furthermore, the efficacy of evidence-based cognitive control interventions aimed at enhancing attention in this group has not been tested. Here we present work aimed at characterizing and enhancing attentional abilities for children with SPD. A sample of 38 SPD and 25 typically developing children were tested on behavioral, neural, and parental measures of attention before and after a 4-week iPad-based at-home cognitive remediation program. At baseline, 54% of children with SPD met or exceeded criteria on a parent report measure for inattention/hyperactivity. Significant deficits involving sustained attention, selective attention and goal management were observed only in the subset of SPD children with parent-reported inattention. This subset of children also showed reduced midline frontal theta activity, an electroencephalographic measure of attention. Following the cognitive intervention, only the SPD children with inattention/hyperactivity showed both improvements in midline frontal theta activity and on a parental report of inattention. Notably, 33% of these individuals no longer met the clinical cut-off for inattention, with the parent-reported improvements persisting for 9 months. These findings support the benefit of a targeted attention intervention for a subset of children with SPD, while simultaneously highlighting the importance of having a multifaceted assessment for individuals with neurodevelopmental conditions to optimally personalize treatment.

  9. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome.

    Science.gov (United States)

    Deng, Zhong; Glousker, Galina; Molczan, Aliah; Fox, Alan J; Lamm, Noa; Dheekollu, Jayaraju; Weizman, Orr-El; Schertzer, Michael; Wang, Zhuo; Vladimirova, Olga; Schug, Jonathan; Aker, Memet; Londoño-Vallejo, Arturo; Kaestner, Klaus H; Lieberman, Paul M; Tzfati, Yehuda

    2013-09-03

    Telomeres repress the DNA damage response at the natural chromosome ends to prevent cell-cycle arrest and maintain genome stability. Telomeres are elongated by telomerase in a tightly regulated manner to ensure a sufficient number of cell divisions throughout life, yet prevent unlimited cell division and cancer development. Hoyeraal-Hreidarsson syndrome (HHS) is characterized by accelerated telomere shortening and a broad range of pathologies, including bone marrow failure, immunodeficiency, and developmental defects. HHS-causing mutations have previously been found in telomerase and the shelterin component telomeric repeat binding factor 1 (TRF1)-interacting nuclear factor 2 (TIN2). We identified by whole-genome exome sequencing compound heterozygous mutations in four siblings affected with HHS, in the gene encoding the regulator of telomere elongation helicase 1 (RTEL1). Rtel1 was identified in mouse by its genetic association with telomere length. However, its mechanism of action and whether it regulates telomere length in human remained unknown. Lymphoblastoid cell lines obtained from a patient and from the healthy parents carrying heterozygous RTEL1 mutations displayed telomere shortening, fragility and fusion, and growth defects in culture. Ectopic expression of WT RTEL1 suppressed the telomere shortening and growth defect, confirming the causal role of the RTEL1 mutations in HHS and demonstrating the essential function of human RTEL1 in telomere protection and elongation. Finally, we show that human RTEL1 interacts with the shelterin protein TRF1, providing a potential recruitment mechanism of RTEL1 to telomeres.

  10. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal–Hreidarsson syndrome

    Science.gov (United States)

    Deng, Zhong; Glousker, Galina; Molczan, Aliah; Fox, Alan J.; Lamm, Noa; Dheekollu, Jayaraju; Weizman, Orr-El; Schertzer, Michael; Wang, Zhuo; Vladimirova, Olga; Schug, Jonathan; Aker, Memet; Londoño-Vallejo, Arturo; Kaestner, Klaus H.; Lieberman, Paul M.; Tzfati, Yehuda

    2013-01-01

    Telomeres repress the DNA damage response at the natural chromosome ends to prevent cell-cycle arrest and maintain genome stability. Telomeres are elongated by telomerase in a tightly regulated manner to ensure a sufficient number of cell divisions throughout life, yet prevent unlimited cell division and cancer development. Hoyeraal–Hreidarsson syndrome (HHS) is characterized by accelerated telomere shortening and a broad range of pathologies, including bone marrow failure, immunodeficiency, and developmental defects. HHS-causing mutations have previously been found in telomerase and the shelterin component telomeric repeat binding factor 1 (TRF1)-interacting nuclear factor 2 (TIN2). We identified by whole-genome exome sequencing compound heterozygous mutations in four siblings affected with HHS, in the gene encoding the regulator of telomere elongation helicase 1 (RTEL1). Rtel1 was identified in mouse by its genetic association with telomere length. However, its mechanism of action and whether it regulates telomere length in human remained unknown. Lymphoblastoid cell lines obtained from a patient and from the healthy parents carrying heterozygous RTEL1 mutations displayed telomere shortening, fragility and fusion, and growth defects in culture. Ectopic expression of WT RTEL1 suppressed the telomere shortening and growth defect, confirming the causal role of the RTEL1 mutations in HHS and demonstrating the essential function of human RTEL1 in telomere protection and elongation. Finally, we show that human RTEL1 interacts with the shelterin protein TRF1, providing a potential recruitment mechanism of RTEL1 to telomeres. PMID:23959892

  11. Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer's dementia.

    Science.gov (United States)

    Park, Jong-Hwan; Park, Hyuntae; Sohn, Sang Wuk; Kim, Sungjae; Park, Kyung Won

    2017-10-01

    To determine the factors that influence diagnosis and differentiation of patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) by comparing memory test results at baseline with those at 1-2-year follow up. We consecutively recruited 23 healthy participants, 44 MCI patients and 27 patients with very mild AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association criteria for probable Alzheimer's disease and Petersen's clinical diagnostic criteria. We carried out detailed neuropsychological tests, including the Story Recall Test (SRT) and the Seoul Verbal Learning Test, for all participants. We defined study participants as the "progression group" as follows: (i) participants who showed conversion to dementia from the MCI state; and (ii) those with dementia who showed more than a three-point decrement in their Mini-Mental State Examination scores with accompanying functional decline from baseline status, which were ascertained by physician's clinical judgment. The SRT delayed recall scores were significantly lower in the patients with mild AD than in those with MCI and after progression. Lower (relative risk 1.1, 95% confidence interval 0.1-1.6) and higher SRT delayed recall scores (relative risk 2.1, confidence interval 1.0-2.8), and two-test combined immediate and delayed recall scores (relative risk 2.0, confidence interval 0.9-2.3; and relative risk 2.8, confidence interval 1.1-4.2, respectively) were independent predictors of progression in a stepwise multiple adjusted Cox proportional hazards model, with age, sex, depression and educational level forced into the model. The present study suggests that the SRT delayed recall score independently predicts progression to dementia in patients with MCI. Geriatr Gerontol Int 2017; 17: 1603-1609. © 2016 Japan Geriatrics Society.

  12. Thalamic metabolic alterations with cognitive dysfunction in idiopathic trigeminal neuralgia: a multivoxel spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuan; Bao, Faxiu; Ma, Shaohui; Guo, Chenguang; Jin, Chenwang; Zhang, Ming [First Affiliated Hospital of Xi' an Jiaotong University, Department of Medical Imaging, Xi' an, Shaanxi (China); Li, Dan [First Affiliated Hospital of Xi' an Jiaotong University, Department of Respiratory and Critical Care Medicine, Xi' an, Shaanxi (China)

    2014-08-15

    Although abnormalities in metabolite compositions in the thalamus are well described in patients with idiopathic trigeminal neuralgia (ITN), differences in distinct thalamic subregions have not been measured with proton magnetic resonance spectroscopy ({sup 1}H-MRS), and whether there are correlations between thalamic metabolites and cognitive function still remain unknown. Multivoxel MRS was recorded to investigate the metabolic alterations in the thalamic subregions of patients with ITN. The regions of interest were localized in the anterior thalamus (A-Th), intralaminar portion of the thalamus (IL-Th), posterior lateral thalamus (PL-Th), posterior medial thalamus (PM-Th), and medial and lateral pulvinar of the thalamus (PuM-Th and PuL-Th). The N-acetylaspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) ratios were measured in the ITN and control groups. Scores of the visual analogue scale (VAS) and the Montreal Cognitive Assessment (MoCA) were analyzed to correlate with the neuroradiological findings. The NAA/Cr ratio in the affected side of PM-Th and PL-Th in ITN patients was statistically lower than that in the corresponding regions of the thalamus in controls. The NAA/Cr ratio in the affected PM-Th was negatively associated with VAS and disease duration. Furthermore, decreases of NAA/Cr and Cho/Cr were detected in the affected side of IL-Th, and lower Cho/Cr was positively correlated with MoCA values in the ITN group. Our result of low level of NAA/Cr in the affected PM-Th probably serves as a marker of the pain-rating index, and decreased Cho/Cr in IL-Th may be an indicator of cognitive disorder in patients with ITN. (orig.)

  13. Lesion load may predict long-term cognitive dysfunction in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Francesco Patti

    Full Text Available Magnetic Resonance Imaging (MRI techniques provided evidences into the understanding of cognitive impairment (CIm in Multiple Sclerosis (MS.To investigate the role of white matter (WM and gray matter (GM in predicting long-term CIm in a cohort of MS patients.303 out of 597 patients participating in a previous multicenter clinical-MRI study were enrolled (49.4% were lost at follow-up. The following MRI parameters, expressed as fraction (f of intracranial volume, were evaluated: cerebrospinal fluid (CSF-f, WM-f, GM-f and abnormal WM (AWM-f, a measure of lesion load. Nine years later, cognitive status was assessed in 241 patients using the Symbol Digit Modalities Test (SDMT, the Semantically Related Word List Test (SRWL, the Modified Card Sorting Test (MCST, and the Paced Auditory Serial Addition Test (PASAT. In particular, being SRWL a memory test, both immediate recall and delayed recall were evaluated. MCST scoring was calculated based on the number of categories, number of perseverative and non-perseverative errors.AWM-f was predictive of an impaired performance 9 years ahead in SDMT (OR 1.49, CI 1.12-1.97 p = 0.006, PASAT (OR 1.43, CI 1.14-1.80 p = 0.002, SRWL-immediate recall (OR 1.72 CI 1.35-2.20 p<0.001, SRWL-delayed recall (OR 1.61 CI 1.28-2.03 p<0.001, MCST-category (OR 1.52, CI 1.2-1.9 p<0.001, MCST-perseverative error(OR 1.51 CI 1.2-1.9 p = 0.001, MCST-non perseverative error (OR 1.26 CI 1.02-1.55 p = 0.032.In our large MS cohort, focal WM damage appeared to be the most relevant predictor of the long-term cognitive outcome.

  14. Infection related renal impairment: a major cause of acute allograft dysfunction.

    Science.gov (United States)

    Nampoory, Mangalathillam R N; Johny, Kaivilayil V; Costandy, Jamal N; Nair, Madhavan P; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, Mustafa

    2003-06-01

    We prospectively analyzed the impact of post-transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40+14 years). During the follow-up period, 52 patients expired and 64 lost on followup. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100+90.2) than that of acute rejection (166+127.1), but was more than that in cyclosporine toxicity (50+42.2). Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=orEcoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR.

  15. Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B.; Ahmed, Juhie; Cha, Danielle S.

    2017-01-01

    . There was a significant increase in lipase (pvalues were above the upper limit of normality. Limitations Small sample size, open-label design, lack of a placebo group. Conclusions Liraglutide was safe and well tolerated by a sample of non-diabetic individuals with mood disorders and had beneficial...... score (age and education corrected) (Cohen's d=0.64, p=0.009) and in a composite Z-score comprising multiple cognitive tests (i.e. Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop test) (Cohen's d=0.77, p

  16. Dysfunctional freezing responses to approaching stimuli in persons with a looming cognitive style for physical threats

    Directory of Open Access Journals (Sweden)

    John H. Riskind

    2016-04-01

    Full Text Available Immobilizing freezing responses are associated with anxiety and may be etiologically related to several anxiety disorders. Although recent studies have sought to investigate the underlying mechanisms in freezing responses that are so problematic in many forms of anxiety, cognitive factors related to anxiety have not been investigated. This study was designed to investigate the potential moderating role of a well-documented cognitive vulnerability to anxiety, the Looming Cognitive Style (i.e., LCS; Riskind et al., 2000, which assesses the extent to which individuals tend to routinely interpret ambiguous threats (e.g., physical or social threats in a biased manner as approaching. We assessed participants’ Reaction Times (RTs when they made judgments about images of animals that differed in threat valence (threat or neutral and motion direction (approach or recede. As expected, LCS for concerns about the approach of physical dangers appeared to moderate freeze reactions. Individuals who were high on this LCS factor tended to generally exhibit a freeze-response (slower RTs and this was independent of the threat valence or motion direction of the animals. These general freezing reactions were in stark contrast to those of individuals who were low on the LCS factor for concerns about the approach of physical dangers. These participants tended to exhibit more selective and functional freezing responses that occurred only to threatening animals with approach motion; they did not exhibit freezing to neutral stimuli or any stimuli with receding motion. These findings did not appear to be explicable by a general slowing of RTs for the participants with high LCS. Moreover, the LCS factor for concerns about social threats (such as rejection or embarrassment was not related to differences in freezing; there was also no additional relationship of freezing to behavioral inhibition scores on the Behavioral Inhibition System and the Behavioral Activation System

  17. Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients.

    Science.gov (United States)

    Haring, L; Müürsepp, A; Mõttus, R; Ilves, P; Koch, K; Uppin, K; Tarnovskaja, J; Maron, E; Zharkovsky, A; Vasar, E; Vasar, V

    2016-07-01

    In studies using magnetic resonance imaging (MRI), some have reported specific brain structure-function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS). Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS. Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS. Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS.

  18. Radiation-induced cognitive dysfunction in 4-month old male wistar rat

    International Nuclear Information System (INIS)

    Lamproglou, I.; Bok, B.; Vranckx, R.; Delattre, J.Y.; Boisserie, G.; Mazeron, J.J.; Baillet, F.

    1997-01-01

    Behavioral dysfunction of memory process arising 4 months after whole brain irradiation (30 Gy/10 fractions/12 days) has been demonstrated in 16-27 month old rats, as compared with non irradiated rats. This study was therefore aimed at delivering the same irradiation in young rats and comparing results with those previously obtained in old rats. Thirty-three 4-month old rats were included into the study. Eighteen received whole brain irradiation (30 Gy/10 fractions/12 days), and 18 were given sham irradiation. Sequential behavior studies were done before irradiation and during the 7 months following irradiation. Significant decrease in memory function was observed in irradiated rats 1 month (p<0.001), 3 months (p<0.013), and 6 months (p=0.007) post-irradiation. This was accompanied by learning deficit 1 month (p=0.01), 4.5 months (p=0.003), and 7 months (p=0.009) post-irradiation. Response to radiation therapy observed in young rats differed from that observed in old rats. Young rats showed earlier decrease in memory function than old rats, but this deficit also arose earlier in young rats than in old rats. In two cases this deficit was permanent. (authors)

  19. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.

    Science.gov (United States)

    Ahmad, Ashfaq; Ali, Tahir; Park, Hyun Young; Badshah, Haroon; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-04-01

    Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ 1-42 mouse model of AD. Single intracerebroventricular injections of Aβ 1-42 (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after Aβ 1-42 injection significantly decreased the Aβ 1-42 -induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ 1-42 -induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test. Fisetin significantly activated p-PI3K, p-Akt (Ser 473), and p-GSK3β (Ser 9) expression in Aβ 1-42 -treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by Aβ 1-42 injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in Aβ 1-42 -treated mice. Our results suggest that fisetin has a potent neuroprotective effect against Aβ 1-42 -induced neurotoxicity. These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as AD.

  20. Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression

    Directory of Open Access Journals (Sweden)

    Lawyer Glenn

    2006-08-01

    Full Text Available Abstract Background Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. Methods Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. Results Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was

  1. Variable lung protective mechanical ventilation decreases incidence of postoperative delirium and cognitive dysfunction during open abdominal surgery.

    Science.gov (United States)

    Wang, Ruichun; Chen, Junping; Wu, Guorong

    2015-01-01

    Postoperative cognitive dysfunction (POCD) is a subtle impairment of cognitive abilities and can manifest on different neuropsychological features in the early postoperative period. It has been proved that the use of mechanical ventilation (MV) increased the development of delirium and POCD. However, the impact of variable and conventional lung protective mechanical ventilation on the incidence of POCD still remains unknown, which was the aim of this study. 162 patients scheduled to undergo elective gastrointestinal tumor resection via laparotomy in Ningbo No. 2 hospital with expected duration >2 h from June, 2013 to June, 2015 were enrolled in this study. Patients included were divided into two groups according to the scheme of lung protective MV, variable ventilation group (VV group, n=79) and conventional ventilation group (CV group, n=83) by randomization performed by random block randomization. The plasma levels of inflammatory cytokines, characteristics of the surgical procedure, incidence of delirium and POCD were collected and compared. Postoperative delirium was detected in 36 of 162 patients (22.2%) and 12 patients of these (16.5%) belonged to the VV group while 24 patients (28.9%) were in the CV group (P=0.036). POCD on the seventh postoperative day in CV group (26/83, 31.3%) was increased in comparison with the VV group (14/79, 17.7%) with significant statistical difference (P=0.045). The levels of inflammatory cytokines were all significantly higher in CV group than those in VV group on the 1st postoperative day (Pprotective MV decreased the incidence of postoperative delirium and POCD by reducing the systemic proinflammatory response.

  2. The interplay of BDNF-TrkB with NMDA receptor in propofol-induced cognition dysfunction : Mechanism for the effects of propofol on cognitive function.

    Science.gov (United States)

    Zhou, Junfei; Wang, Fang; Zhang, Jun; Li, Jianfeng; Ma, Li; Dong, Tieli; Zhuang, Zhigang

    2018-04-05

    The aim of the present study was to verify whether propofol impaired learning and memory through the interplay of N-methyl-D-aspartate (NMDA) receptor with brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway. 120 Sprague-Dawley (SD) rats were randomly assigned into eight groups. Experimental drugs including saline, intralipid, propofol, N-methyl-D-aspartate (NMDA), 7,8-dihydroxyflavone (7,8-DHF), K252a and MK-801. Spatial learning and memory of rats were tested by the Morris water maze (MWM) test. The mRNA and protein expression were determined by immunohistochemistry, RT-PCR and western blot. Finally, hippocampus cells proliferation and apoptosis were examined by PCNA immunohistochemistry and TUNEL respectively. The memory and learning was diminished in the propofol exposure group, however, the impaired memory and learning of rats were improved with the addition of NMDA and 7,8-DHF, while the improvement of memory and learning of rats were reversed with the addition of K252a and MK-801. In addition, the mRNA and protein expression levels and hippocampus cells proliferation were the same trend with the results of the MWM test, while apoptosis in hippocampus was reversed. The propofol can impair memory and learning of rats and induce cognition dysfunction through the interplay of NMDA receptor and BDNF-TrkB-CREB signaling pathway.

  3. Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-κB/MAPK pathway.

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    Ding, Yongbo; Shi, Cunxian; Chen, Linjing; Ma, Piliang; Li, Kezhong; Jin, Jin; Zhang, Qingfeng; Li, Aizhi

    2017-12-01

    The present study investigated the effects of andrographolide on postoperative cognitive dysfunction (POCD) in aged rats to gain insight of the underlying mechanism, which may provide theoretical basis for the clinical application of andrographolide to prevent POCD in older patients. Thirty aged male rats were randomly assigned to 3 groups: Control, model and andrographolide groups. The Morris water maze test was used to examine the spatial memory and learning ability of the rats postoperatively. The histological alterations of neuronal cells in the hippocampus were visualized by H&E staining. The serum levels of neuron-specific enolase (NSE), human soluble protein-100β (S-100β) and the inflammation factors of interluekin (IL)-1β, IL-6 and TNF-α involved in the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway were detected by ELISA. The NF-κB/MAPK signaling pathway-associated proteins in rat serum were detected by western blotting. Following andrographolide treatment, the rats significantly gained learning ability after surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery. Andrographolide decreased NSE, S-100β, and the inflammation factors, IL-6, IL-1β and TNF-α in serum. Andrographolide reduced NF-κB/MAPK pathway-associated protein expression. Andrographolide ameliorated POCD in aged rats following surgery. The underlying mechanism may be associated with the downregulation the inflammatory factors and NF-κB/MAPK-associated protein expression.

  4. The role of self-awareness and cognitive dysfunction in Parkinson's disease with and without impulse-control disorder.

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    Mack, Joel; Okai, David; Brown, Richard G; Askey-Jones, Sally; Chaudhuri, K Ray; Martin, Anne; Samuel, Michael; David, Anthony S

    2013-01-01

    The aim of this study was to investigate the clinical, neuropsychological, and self-awareness correlates of impulse-control disorder (ICD) in a group of 17 Parkinson's disease (PD) subjects with an active ICD and a comparison group of 17 PD subjects without ICD. Self-awareness was assessed with the Beck Cognitive Insight Scale and patient-caregiver discrepancy scores from ratings on the Dysexecutive Questionnaire and the Everyday Memory Questionnaire-Revised. Self-awareness was comparable or increased in those with ICD, versus those without, and measures of neuropsychological functioning did not differ between the two groups. Those with ICD had more motor complications of PD therapy and were more likely to be on an antidepressant than those without ICD, whereas dopaminergic medication profiles were comparable between the two groups. In this group, PD patients with current ICDs were aware of their impulsivity. Although executive dysfunction may contribute to ICD behavior, it is not a necessary component. The awareness of the inability to resist these motivated behaviors may be a source of increased depression.

  5. Ginsenoside Re Ameliorates Brain Insulin Resistance and Cognitive Dysfunction in High Fat Diet-Induced C57BL/6 Mice.

    Science.gov (United States)

    Kim, Jong Min; Park, Chang Hyeon; Park, Seon Kyeong; Seung, Tae Wan; Kang, Jin Yong; Ha, Jeong Su; Lee, Du Sang; Lee, Uk; Kim, Dae-Ok; Heo, Ho Jin

    2017-04-05

    The ameliorating effects of ginsenoside Re (G Re) on high fat diet (HFD)-induced insulin resistance in C57BL/6 mice were investigated to assess its physiological function. In the results of behavioral tests, G Re improved cognitive dysfunction in diabetic mice using Y-maze, passive avoidance, and Morris water maze tests. G Re also significantly recovered hyperglycemia and fasting blood glucose level. In the results of serum analysis, G Re decreased triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDLC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) and increased the ratio of high-density lipoprotein cholesterol (HDLC). G Re regulated acetylcholine (ACh), acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and oxidized glutathione (GSH)/total GSH by regulating the c-Jun N-terminal protein kinase (JNK) pathway. These findings suggest that G Re could be used to improve HFD-induced insulin resistance condition by ameliorating hyperglycemia via protecting the cholinergic and antioxidant systems in the mouse brains.

  6. Association Between ABO Blood Type and Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Unilateral Total Hip Arthroplasty Surgery in China.

    Science.gov (United States)

    Li, Jie; Zhou, Jun; Wan, Yunqiang; Liu, Li; Ou, Cehua

    2017-05-28

    BACKGROUND Postoperative cognitive dysfunction (POCD) is a postoperative complication after surgery and anesthesia. Whether ABO blood types are associated with POCD in elderly patients undergoing unilateral total hip arthroplasty surgery in China is unclear. MATERIAL AND METHODS Firstly, 142 elderly patients were divided into a POCD group and a non-POCD group according to the Mini Mental State Examination (MMSE) scores and ABO blood types were analyzed. Secondly, according to ABO blood type, the selected 226 patients were divided into 4 groups: type A group, type B group, type AB group, and type O group. Then, all patients completed the MMSE before and after surgery. Finally, the occurrence of POCD was recorded and related data were analyzed. RESULTS Firstly, there was a significant difference in both groups in terms of distribution of ABO blood types, and elderly patients who developed POCD were more likely to have type A blood and less likely to have type O blood. Secondly, compared with elderly patients with type A blood, those with type O had higher MMSE scores on the first day and the seventh day after surgery. Finally, the risk of developing POCD was significantly higher in patients with type A blood and on the first day and the seventh day after surgery the risk of developing POCD was significantly lower in patients with type O blood. CONCLUSIONS Elderly patients with type A blood have higher risk of developing early POCD and those with type O blood have less risk of developing early POCD.

  7. Cognitive dysfunctions in middle-aged type 2 diabetic patients and neuroimaging correlations: a cross-sectional study.

    Science.gov (United States)

    García-Casares, Natalia; Jorge, Ricardo E; García-Arnés, Juan A; Acion, Laura; Berthier, Marcelo L; Gonzalez-Alegre, Pedro; Nabrozidis, Alejandro; Gutiérrez, Antonio; Ariza, María José; Rioja, Jose; González-Santos, Pedro

    2014-01-01

    The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations. We compared 25 subjects with T2DM aged 45-65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET. T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001). T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

  8. Accumulation of Exogenous Amyloid-Beta Peptide in Hippocampal Mitochondria Causes Their Dysfunction: A Protective Role for Melatonin

    Directory of Open Access Journals (Sweden)

    Sergio Rosales-Corral

    2012-01-01

    Full Text Available Amyloid-beta (Aβ pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS. Monomers and oligomers of Aβ have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer’s disease (AD brain. We hypothesize that the internalization of extracellular Aβ aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Aβ into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Aβ into the cell. Thereafter, Aβ appears in mitochondria where it is linked to alterations in the ionic gradient across the inner mitochondrial membrane. This effect is accompanied by disruption of subcellular structure, oxidative stress, and a significant reduction in both the respiratory control ratio and in the hydrolytic activity of ATPase. Orally administrated melatonin reduced oxidative stress, improved the mitochondrial respiratory control ratio, and ameliorated the energy imbalance.

  9. Cardiopulmonary dysfunction in the Osteogenesis imperfecta mouse model Aga2 and human patients are caused by bone-independent mechanisms.

    Science.gov (United States)

    Thiele, Frank; Cohrs, Christian M; Flor, Armando; Lisse, Thomas S; Przemeck, Gerhard K H; Horsch, Marion; Schrewe, Anja; Gailus-Durner, Valerie; Ivandic, Boris; Katus, Hugo A; Wurst, Wolfgang; Reisenberg, Catherine; Chaney, Hollis; Fuchs, Helmut; Hans, Wolfgang; Beckers, Johannes; Marini, Joan C; Hrabé de Angelis, Martin

    2012-08-15

    Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with skeletal dysplasia of varying severity, predominantly caused by mutations in the collagen I genes (COL1A1/COL1A2). Extraskeletal findings such as cardiac and pulmonary complications are generally considered to be significant secondary features. Aga2, a murine model for human OI, was systemically analyzed in the German Mouse Clinic by means of in vivo and in vitro examinations of the cardiopulmonary system, to identify novel mechanisms accounting for perinatal lethality. Pulmonary and, especially, cardiac fibroblast of perinatal lethal Aga2/+ animals display a strong down-regulation of Col1a1 transcripts in vivo and in vitro, resulting in a loss of extracellular matrix integrity. In addition, dysregulated gene expression of Nppa, different types of collagen and Agt in heart and lung tissue support a bone-independent vicious cycle of heart dysfunction, including hypertrophy, loss of myocardial matrix integrity, pulmonary hypertension, pneumonia and hypoxia leading to death in Aga2. These murine findings are corroborated by a pediatric OI cohort study, displaying significant progressive decline in pulmonary function and restrictive pulmonary disease independent of scoliosis. Most participants show mild cardiac valvular regurgitation, independent of pulmonary and skeletal findings. Data obtained from human OI patients and the mouse model Aga2 provide novel evidence for primary effects of type I collagen mutations on the heart and lung. The findings will have potential benefits of anticipatory clinical exams and early intervention in OI patients.

  10. MRI T2 relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy

    OpenAIRE

    Kunigiri, Girish; Jayakumar, P. N.; Janakiramaiah, N.; Gangadhar, B. N.

    2007-01-01

    Background: Although electroconvulsive therapy (ECT) causes no structural brain damage, recent studies reported altered brain perfusion acutely following ECT. This is in keeping with brain edema which was noted in animal experiments following electroconvulsive shock. Aim: This study examined alteration in magnetic resonance imaging (MRI) T2 relaxation time, a measure of brain edema, and its relation to therapeutic efficacy, orientation and memory impairment with ECT. Materials and Methods: Fi...

  11. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

    Science.gov (United States)

    Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

    2018-06-01

    Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

  12. Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble α-synuclein in neurons.

    Science.gov (United States)

    Schapansky, Jason; Khasnavis, Saurabh; DeAndrade, Mark P; Nardozzi, Jonathan D; Falkson, Samuel R; Boyd, Justin D; Sanderson, John B; Bartels, Tim; Melrose, Heather L; LaVoie, Matthew J

    2018-03-01

    Missense mutations in the multi-domain kinase LRRK2 cause late onset familial Parkinson's disease. They most commonly with classic proteinopathy in the form of Lewy bodies and Lewy neurites comprised of insoluble α-synuclein, but in rare cases can also manifest tauopathy. The normal function of LRRK2 has remained elusive, as have the cellular consequences of its mutation. Data from LRRK2 null model organisms and LRRK2-inhibitor treated animals support a physiological role for LRRK2 in regulating lysosome function. Since idiopathic and LRRK2-linked PD are associated with the intraneuronal accumulation of protein aggregates, a series of critical questions emerge. First, how do pathogenic mutations that increase LRRK2 kinase activity affect lysosome biology in neurons? Second, are mutation-induced changes in lysosome function sufficient to alter the metabolism of α-synuclein? Lastly, are changes caused by pathogenic mutation sensitive to reversal with LRRK2 kinase inhibitors? Here, we report that mutation of LRRK2 induces modest but significant changes in lysosomal morphology and acidification, and decreased basal autophagic flux when compared to WT neurons. These changes were associated with an accumulation of detergent-insoluble α-synuclein and increased neuronal release of α-synuclein and were reversed by pharmacologic inhibition of LRRK2 kinase activity. These data demonstrate a critical and disease-relevant influence of native neuronal LRRK2 kinase activity on lysosome function and α-synuclein homeostasis. Furthermore, they also suggest that lysosome dysfunction, altered neuronal α-synuclein metabolism, and the insidious accumulation of aggregated protein over decades may contribute to pathogenesis in this late-onset form of familial PD. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Does incongruence of lexicosemantic and prosodic information cause discernible cognitive conflict?

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    Mitchell, Rachel L C

    2006-12-01

    We are often required to interpret discordant emotional signals. Whereas equivalent cognitive paradigms cause noticeable conflict via their behavioral and psychophysiological effects, the same may not necessarily be true for discordant emotions. Skin conductance responses (SCRs) and heart rates (HRs) were measured during a classic Stroop task and one in which the emotions conveyed by lexicosemantic content and prosody were congruent or incongruent. The participants' task was to identify the emotion conveyed by lexicosemantic content or prosody. No relationship was observed between HR and congruence. SCR was higher during incongruent than during congruent conditions of the experimental task (as well as in the classic Stroop task), but no difference in SCR was observed in a comparison between congruence effects during lexicosemantic emotion identification and those during prosodic emotion identification. It is concluded that incongruence between lexicosemantic and prosodic emotion does cause notable cognitive conflict. Functional neuroanatomic implications are discussed.

  14. Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment.

    Science.gov (United States)

    Spellmann, Ilja; Riedel, Michael; Städtler, Julia; Zill, Peter; Obermeier, Michael; Cerovecki, Anja; Dehning, Sandra; Schennach, Rebecca; Epple, Maria; Opgen-Rhein, Markus; Müller, Norbert; Bondy, Brigitta; Möller, Hans-Jürgen; Musil, Richard

    2017-07-01

    NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics. Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. 167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed. Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

  15. Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

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    Yanagiha, Kumi; Ishii, Kazuhiro; Tamaoka, Akira

    2017-02-01

    Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

  16. Olive Oil Supplements Ameliorate Endothelial Dysfunction Caused by Concentrated Ambient Particulate Matter Exposure in Healthy Human Volunteers

    Science.gov (United States)

    Context: Exposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for clinical cardiovascular events and progression of atherosclerosis. Dietary supplements such as olive oil and fish oil have beneficial effects on endothelial function, and ther...

  17. Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined 'Timed Up and Go' Test (iTUG.

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    Maxime Geiger

    Full Text Available Motor imagery (MI capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known.To assess temporal congruence between the Timed Up and Go test (TUG and the imagined TUG (iTUG tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence.TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA, the Frontal Assessment Battery at Bedside (FAB and the Bells Test.The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02. Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013, likely suggesting that impairment of attention was a contributing factor.These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction.

  18. Neuropsychological Testing and Machine Learning Distinguish Alzheimer’s Disease from Other Causes for Cognitive Impairment

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    Helmut Hildebrandt

    2017-04-01

    Full Text Available With promising results in recent treatment trials for Alzheimer’s disease (AD, it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET or inaccurate Magnetic Resonance Imaging (MRI. This study investigates the potential of neuropsychological testing (NPT to specifically identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI or dementia for various causes. Patients were divided into an early stage and a late stage group according to their Mini Mental State Examination (MMSE score and labeled as AD or non-AD patients based on a post-mortem validated threshold of the ratio between total tau and beta amyloid in the cerebrospinal fluid (CSF; Total tau/Aβ(1–42 ratio, TB ratio. All patients completed the established Consortium to Establish a Registry for Alzheimer’s Disease—Neuropsychological Assessment Battery (CERAD-NAB test battery and two additional newly-developed neuropsychological tests (recollection and verbal comprehension that aimed at carving out specific Alzheimer-typical deficits. Based on these test results, an underlying AD (pathologically increased TB ratio was predicted with a machine learning algorithm. To this end, the algorithm was trained in each case on all patients except the one to predict (leave-one-out validation. In the total group, 82% of the patients could be correctly identified as AD or non-AD. In the early group with small general cognitive impairment, classification accuracy was increased to 89%. NPT thus seems to be capable of discriminating between AD patients and patients with cognitive impairment due to other neurodegenerative or vascular causes with a high accuracy, and may be used for screening in clinical routine and drug studies, especially in the early course of this disease.

  19. Aortic Blood Flow Reversal Determines Renal Function: Potential Explanation for Renal Dysfunction Caused by Aortic Stiffening in Hypertension.

    Science.gov (United States)

    Hashimoto, Junichiro; Ito, Sadayoshi

    2015-07-01

    Aortic stiffness determines the glomerular filtration rate (GFR) and predicts the progressive decline of the GFR. However, the underlying pathophysiological mechanism remains obscure. Recent evidence has shown a close link between aortic stiffness and the bidirectional (systolic forward and early diastolic reverse) flow characteristics. We hypothesized that the aortic stiffening-induced renal dysfunction is attributable to altered central flow dynamics. In 222 patients with hypertension, Doppler velocity waveforms were recorded at the proximal descending aorta to calculate the reverse/forward flow ratio. Tonometric waveforms were recorded to measure the carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities, to estimate the aortic pressure from the radial waveforms, and to compute the aortic characteristic impedance. In addition, renal hemodynamics was evaluated by duplex ultrasound. The estimated GFR was inversely correlated with the aortic pulse wave velocity, reverse/forward flow ratio, pulse pressure, and characteristic impedance, whereas it was not correlated with the peripheral pulse wave velocity or mean arterial pressure. The association between aortic pulse wave velocity and estimated GFR was independent of age, diabetes mellitus, hypercholesterolemia, and antihypertensive medication. However, further adjustment for the aortic reverse/forward flow ratio and pulse pressure substantially weakened this association, and instead, the reverse/forward flow ratio emerged as the strongest determinant of estimated GFR (P=0.001). A higher aortic reverse/forward flow ratio was also associated with lower intrarenal forward flow velocities. These results suggest that an increase in aortic flow reversal (ie, retrograde flow from the descending thoracic aorta toward the aortic arch), caused by aortic stiffening and impedance mismatch, reduces antegrade flow into the kidney and thereby deteriorates renal function. © 2015 American Heart Association

  20. Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Anjali Kumari

    Full Text Available Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl ethylenediamine (TPEN and Zinc Sulfate (ZnSO4. Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death

  1. Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.

    Science.gov (United States)

    Kina-Tanada, Mika; Sakanashi, Mayuko; Tanimoto, Akihide; Kaname, Tadashi; Matsuzaki, Toshihiro; Noguchi, Katsuhiko; Uchida, Taro; Nakasone, Junko; Kozuka, Chisayo; Ishida, Masayoshi; Kubota, Haruaki; Taira, Yuji; Totsuka, Yuichi; Kina, Shin-Ichiro; Sunakawa, Hajime; Omura, Junichi; Satoh, Kimio; Shimokawa, Hiroaki; Yanagihara, Nobuyuki; Maeda, Shiro; Ohya, Yusuke; Matsushita, Masayuki; Masuzaki, Hiroaki; Arasaki, Akira; Tsutsui, Masato

    2017-06-01

    Nitric oxide (NO) is synthesised not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice. To this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of L-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water. Three months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. These results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.

  2. Is Long Term Duration of Diabetes is a Factor to Cause Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus?

    Directory of Open Access Journals (Sweden)

    Siva Prasad Palem

    2017-12-01

    Full Text Available Introduction: Endothelial Dysfunction (ED is an earliest pathological process of atherosclerosis. Endothelium regulates vascular tone, platelet activity, leukocyte adhesion and thrombosis. Impaired function of endothelium initiates the development of atherosclerosis. Nitric oxide is one of the most effective endogenous vasodilator and also a marker for ED. Aim: To assess whether long term duration of diabetes is a factor to cause ED and its complications in patients with Type 2 diabetes mellitus. Hence, the study has been designed to assess the ED in patients with long term duration of Type 2 diabetes for early prediction of vascular complications. Materials and Methods: The study was conducted on 47 Type 2 diabetic subjects. Among these 27 subjects with 5 years duration of diabetes (Group-II. Glucose, HbA1c, BMI and lipid profile were estimated by well established methods in auto-analyzer, MDA by Thiobarbituric Acid Reactive Substances (TBARS, total antioxidant capacity as Ferric Reducing Ability of Plasma (FRAP and NO was estimated by kinetic cadmium reduction method using spectrophotometer. Statistical analysis was performed by “Kruskal-Wallis” test. Result: Significantly low level of NO was identified in Type 2 diabetic patients with >5 years duration of disease compared to 5 years duration of diabetes and no significant difference in the level of FRAP among the study groups. It has also shown significantly high level of age in >5 years duration of Type 2 diabetes than <5 years. But, no significant differences in the levels of HbA1c, lipid profile were identified between two study groups. Conclusion: Age and oxidative stress (lipid peroxidation has been recognized as risk factors for ED and future complications in patients with more than 5 years duration of Type 2 diabetes.

  3. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

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    Jin-Xiu Zhang

    Full Text Available β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR, feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+,K(+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD, catalase (CAT, glutathione-S-transferase (GST, glutathione peroxidase (GPx and glutathione reductase (GR activities and glutathione (GSH content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8, tumor necrosis factor-α (TNF-α, and transforming growth factor-β (TGF-β genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  4. Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some anesthetic drugs in the hippocampal area of rats.

    Science.gov (United States)

    Alirezaei, Masoud; Rezaei, Maryam; Hajighahramani, Shahin; Sookhtehzari, Ali; Kiani, Katayoun

    2017-01-01

    The present study was designed to evaluate the antioxidant effects of oleuropein against oxidative stress in the hippocampal area of rats. We used seven experimental groups as follows: Control, Propofol, Propofol-Ketamine (Pro.-Ket.), Xylazine-Ketamine (Xyl.-Ket.), and three oleuropein-pretreated groups (Ole.-Pro., Ole.-Pro.-Ket. and Ole.-Xyl.-Ket.). The oleuropein-pretreated groups received oleuropein (15 mg/kg body weight as orally) for 10 consecutive days. Propofol 100 mg/kg, xylazine 3 mg/kg, and ketamine 75 mg/kg once as ip was used on the 11th day of treatment. Spatial memory impairment and antioxidant status of hippocampus were measured via Morris water maze, lipid peroxidation marker, and antioxidant enzyme activities. Spatial memory impairment and lipid peroxidation significantly increased in Xyl.-Ket.-treated rats in comparison to the control, propofol, Ole.-Pro. and Ole.-Pro.-Ket. groups. Oleuropein pretreatment significantly reversed spatial memory impairment and lipid peroxidation in the Ole.-Xyl.-Ket. group as compared to the Xyl.-Ket.-treated rats. There was no significant difference between the control and the propofol group in lipid peroxidation and spatial memory status. Superoxide dismutase and catalase activities both significantly decreased in Xyl.-Ket.-treated rats when compared to the control, propofol, Ole.-Pro., Ole.-Pro.-Ket., and Ole.-Xyl.-Ket. groups. In contrast, glutathione peroxidase activity in Xyl.-Ket.-treated rats significantly increased as compared to the control, propofol, Pro.-Ket., Ole.-Pro., and Ole.-Pro.-Ket. groups. We concluded that xylazine in combination with ketamine is an oxidative anesthetic drug and oleuropein pretreatment attenuates cognitive dysfunction and oxidative stress induced by anesthesia in the hippocampal area of rats. We also confirmed the antioxidant properties of propofol as a promising antioxidant anesthetic agent.

  5. Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure.

    Science.gov (United States)

    Yokota, Junichi; Ogawa, Yoshiko; Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro

    2016-01-01

    Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia.

  6. Pre-existing weakness is critical for the occurrence of postoperative cognitive dysfunction in mice of the same age.

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    Yujie Tang

    Full Text Available Occurrence of postoperative cognitive dysfunction (POCD is age-dependent and heterogenous. Factors deciding the occurrence of POCD in patients of the same age undergone same surgeries remain unclear. Here we investigated the effects of pre-existing weakness on the occurrence of POCD in mice of the same age. Pre-existing weakness of mice was induced by intraperitoneal injection of lipopolysaccharide (8mg/kg and was evaluated by physical frailty index (by open field test, neuroinflammation level (by Iba1 immunostaining and inflammatory factors TNF-α and IL-1β, and neuronal activity (by p-CREB immunostaining. POCD was induced by partial hepatolobectomy and was evaluated by puzzle box test and Morris water maze test. The brains were collected to detect the levels of neuroinflammation, synaptophysin and NMDA receptor subunits NR2A, NR2B and NR1 (by western blot, and oxidative stress (by Dihydroethidium. Compared to the normal adult mice of the same age, LPS pretreated mice had increased physical frailty index, higher levels of neuroinflammation, and lower neuronal activity. Partial hepatolobectomy induced obvious impairments in executive function, learning and memory in LPS pretreated mice after surgery, but not in normal mice of the same age. Partial hepatolobectomy also induced heightened neuroinflammation, obvious loss of NMDA receptor subunits, strong oxidative stress in LPS pretreated mice on the 1st and 3rd postoperative day. However, the POCD-associated pathological changes didn't occur in normal mice of the same age after surgery. These results suggest that pre-existing weakness is critical for the occurrence of POCD in mice of the same age.

  7. The Impact of High Versus Low Sedation Dosing Strategy on Cognitive Dysfunction in Survivors of Intensive Care Units: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Porhomayon Jahan

    2015-06-01

    Full Text Available Background: The practice of low vs. high sedation dosing strategy may impact the cognitive and mental health function in the intensive care unit (ICU. We aim to demonstrate that high sedation strategy will result in change of mental health function in ICU patients. Methods: We performed a systemic search and meta-analysis of medical databases in MEDLINE(from 1966 to March 2013 and EMBASE (from 1980 to March 2013, as well as the Cochrane Library using the MESH terms "Intensive Care Unit," and "Mental Health, for assessing the impact of sedation on posttraumatic stress disorder (PTSD or anxiety/depression and deliriumin the mix ICU setting including cardiac surgery patients. A total of 1216 patients were includedin the final analysis.Results: We included 11 studies in the final analysis and concluded that high dose sedationstrategy resulted in higher incidence of cognitive dysfunction with P value of 0.009. Theresult for subgroup of delirium showed P = 0.11 and PTSD/depression or anxiety of P = 0.001,Heterogeneity I2 was 64%. Overall analysis was statistically significant with a P value of 0.002.Conclusion: High sedation dosing strategy will negatively affect cognitive function in criticallyill patients. Large randomized trials are needed to address cognitive dysfunction in subgroup of patients with delirium.

  8. Dietary choline during periadolescence attenuates cognitive damage caused by neonatal maternal separation in male rats.

    Science.gov (United States)

    Moreno Gudiño, Hayarelis; Carías Picón, Diamela; de Brugada Sauras, Isabel

    2017-07-01

    Choline (Ch) is an essential nutrient that acts as a cognitive facilitator when administered during perinatal periods, and it has been recognised as a 'pharmacological' agent that can ease cognitive dysfunctions provoked by exposure to damaging stimuli during early developmental stages. The aim of the present work is to determine whether providing a diet rich in Ch would reduce the severity of the memory deficit provoked by a neonatal stress episode in male adult rats. The effect of Ch on memory was measured using memory tasks such as object and place recognition. Ontogenetic manipulations were conducted during two sensitive developmental periods. During the first post-natal (PN) 14 days, only the male rat pups were selected and half of them were separated from the mother, group maternal separation (MS). Subsequently, during periadolescence (PN 21-60), the rats were exposed to a deficient (DEF = 0 g/kg Ch chloride), sufficient (CON = 1.1 g/kg Ch chloride), or supplemented (SUP = 5 g/kg Ch chloride) diets for this nutrient. The results indicated that for group MS, only rats fed with the SUP diet were able to recognise the familiar object and place that had been experienced 24 hours before, unlike groups DEF and CON. In addition, whereas rats in the non-separated group (No-MS) recognised the object independently of the diet, only rats that received a DEF diet failed to recognise the place, showing that a Ch deficit affects spatial memory tasks. These results show that Ch supplementation during periadolescence can attenuate the memory deficit provoked by extended neonatal stress.

  9. Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

    Science.gov (United States)

    He, Zhi; Liao, Yun; Zheng, Min; Zeng, Fan-Dian; Guo, Lian-Jun

    2008-06-01

    Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.

  10. CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

    Science.gov (United States)

    Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall'Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

    2015-03-26

    Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

  11. CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

    Science.gov (United States)

    Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

    2015-01-01

    Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

  12. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse

    DEFF Research Database (Denmark)

    Schäfer, Carolyn; Guldager, Helle Skov; Jørgensen, H L

    2011-01-01

    and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency...

  13. Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

    Science.gov (United States)

    Cobb, Dustin A.; Bhadra, Rajarshi

    2016-01-01

    CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

  14. Early treatment for IgG4-related disease may prevent cognitive impairment caused by cerebral vasculitis: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Toshihiko Usami

    2018-03-01

    Full Text Available IgG4-related disease (IgG4-RD is a recently recognized disease entity. A 74-year-old male presented with transient headache. He was diagnosed IgG4-RD by pancreatic biopsy at the age of 72. Magnetic Resonance Imaging (MRI showed disseminated cerebral microbleeds and microinfarctions in time and space. It suggested cerebral vasculitis, however any causative factor were not confirmed. IgG4-RD rarely causes cerebral vasculitis. This might be a first case of an asymptomatic cerebral vasculitis due to IgG4-RD. Patient was started on oral prednisolone, and no neurological or neuropsychological symptom was clinically observed. The MRI findings improved after treatment, and revealed no indication of newly lesions at 6-months follow-up. Early treatment for IgG4-RD may be recommended to prevent irreversible cognitive dysfunction. Keywords: IgG4-related disease, Treatment, Cerebral vasculitis

  15. Insulin Protects against Brain Oxidative Stress with an Apparent Effect on Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats.

    Science.gov (United States)

    Ramalingayya, Grandhi Venkata; Sonawane, Vishwajeet; Cheruku, Sri Pragnya; Kishore, Anoop; Nayak, Pawan G; Kumar, Nitesh; Shenoy, Rekha S; Nandakumar, Krishnadas

    2017-01-01

    The present study was aimed at assessing the protective effect of insulin against doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive function for episodic memory was assessed by a novel object recognition task (NORT) in male Wistar rats. Oxidative stress markers-SOD, catalase, glutathione, and lipid peroxidation-in the hippocampus and frontal cortex were assessed using colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50 days) reduced recognition and discriminative indices in NORT with increased oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg, i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin with an increase in the antioxidant defense systems (SOD, catalase, and GSH). Rats treated with combined insulin and DOX spent comparatively more time with the novel object when compared to the non-novel objects; however, the observed difference was not statistically significant. An apparent improvement (p insulin reduces brain oxidative stress and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.

  16. Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria

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    Francesca Nardecchia

    2018-03-01

    Full Text Available We studied group-I metabotropic glutamate (mGlu receptors in Pahenu2 (ENU2 mice, which mimic the genetics and neurobiology of human phenylketonuria (PKU, a metabolic disorder characterized, if untreated, by autism, and intellectual disability (ID. Male ENU2 mice showed increased mGlu5 receptor protein levels in the hippocampus and corpus striatum (but not in the prefrontal cortex whereas the transcript of the mGlu5 receptor was unchanged. No changes in mGlu1 receptor mRNA and protein levels were found in any of the three brain regions of ENU2 mice. We extended the analysis to Homer proteins, which act as scaffolds by linking mGlu1 and mGlu5 receptors to effector proteins. Expression of the long isoforms of Homer was significantly reduced in the hippocampus of ENU2 mice, whereas levels of the short Homer isoform (Homer 1a were unchanged. mGlu5 receptors were less associated to immunoprecipitated Homer in the hippocampus of ENU2 mice. The lack of mGlu5 receptor-mediated long-term depression (LTD in wild-type mice (of BTBR strain precluded the analysis of hippocampal synaptic plasticity in ENU2 mice. We therefore performed a behavioral analysis to examine whether pharmacological blockade of mGlu5 receptors could correct behavioral abnormalities in ENU2 mice. Using the same apparatus we sequentially assessed locomotor activity, object exploration, and spatial object recognition (spatial novelty test after displacing some of the objects from their original position in the arena. Systemic treatment with the mGlu5 receptor antagonist, MPEP (20 mg/kg, i.p., had a striking effect in the spatial novelty test by substantially increasing the time spent in exploring the displaced objects in ENU2 mice (but not in wild-type mice. These suggest a role for mGlu5 receptors in the pathophysiology of ID in PKU and suggest that, also in adult untreated animals, cognitive dysfunction may be improved by targeting these receptors with an appropriate therapy.

  17. Urtica dioica leaves modulates hippocampal smoothened-glioma associated oncogene-1 pathway and cognitive dysfunction in chronically stressed mice.

    Science.gov (United States)

    Patel, Sita Sharan; Mahindroo, Neeraj; Udayabanu, Malairaman

    2016-10-01

    The present study was aimed to evaluate the effect of Urtica dioica (UD) extract against chronic unpredictable stress (CUS)-induced associative memory dysfunction and attempted to explore the possible mechanism. Male Swiss albino mice (25-30g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350mg/kg, p.o.) (CUS+HYP), group IV received Hypericum perforatum extract (350mg/kg, p.o.) (CTRL+HYP); group V was subjected to CUS and received UD extract (50mg/kg, p.o.) (CUS+UD), group VI received UD extract (50mg/kg, p.o.) (CTRL+UD). CUS significantly induced body weight loss (p<0.05) and associative memory impairment in step down task (p<0.05) as compared to control mice. CUS significantly downregulated Smo (p<0.05), Gli1 (p<0.01), cyclin D1 (p<0.05), BDNF (p<0.01), TrKB (p<0.01) and MAPK1 (p<0.01) mRNA expression in hippocampus as compared to control mice. CUS significantly increased the levels of TBARS (p<0.01) and nitric oxide (p<0.001), and decreased catalase (p<0.001) and total thiol (p<0.01) in plasma resulting in oxidative stress and inflammation. Chronic UD administration significantly reverted CUS mediated body weight loss (p<0.05) and cognitive impairment (p<0.05). UD administration significantly decreased the levels of TBARS (p<0.01) and nitric oxide (p<0.05), and increased the levels of catalase (p<0.01) and total thiol (p<0.05) in plasma. Chronic UD administration significantly upregulated hippocampal Smo (p<0.05), Gli1 (p<0.001), cyclin D1 (p<0.05), BDNF (p<0.05), TrKB (p<0.05) and MAPK1 (p<0.05) in stressed mice. Further, UD extract did not reverse cyclopamine induced downregulation of Gli1 and Ptch1 mRNA in hippocampal slices. UD modulated Smo-Gli1 pathway in the hippocampus as well as exerted anti-inflammatory and antioxidant effects. UD extract might prove

  18. Cognitive processes and attitudes in bipolar disorder: a study into personality, dysfunctional attitudes and attention bias in patients with bipolar disorder and their relatives.

    Science.gov (United States)

    Jabben, Nienke; Arts, Baer; Jongen, Ellen M M; Smulders, Fren T Y; van Os, Jim; Krabbendam, Lydia

    2012-12-20

    Research in cognitive processes and attitudes in bipolar disorder is scarce and has provided mixed findings, possibly due to differences in current mood state. It is unclear whether alterations in cognitive processes and attitudes are only related to the depressive mood states of bipolar patients or also represent a vulnerability marker for the development of future (depressive) episodes. This was investigated in the current study. Both implicit (attentional bias for emotional words) and explicit (dysfunctional attitudes and personality characteristics) measures of cognitive processes and attitudes were assessed in 77 bipolar patients with varying levels of depressive symptoms (depressed=17, euthymic n=60), their healthy first-degree relatives (n=39) and a healthy control group (n=61). Analyses of variance were used to investigate differences between groups. Mildly depressed patients with bipolar disorder demonstrated an attentional bias away from positive emotional words and showed increased dysfunctional attitudes and higher levels of neuroticism. Euthymic patients were largely comparable to healthy controls and only differed from controls in higher levels of neuroticism. Relatives were similar to controls on all measures, although they significantly differed from bipolar patients in displaying less neuroticism and more extraversion. No firm conclusions regarding causality can be drawn from the associations that were found between cognitive processes and attitudes and the evolution of mood symptoms in bipolar disorder. Alterations in cognitive processes and attitudes in bipolar patients appear to be mostly related to the expression of mood symptomatology rather than to the vulnerability for bipolar disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Diagnosis and treatment of cognitive deficits caused by radiation in patients with brain tumours

    International Nuclear Information System (INIS)

    Ishiuchi, Shogo

    2011-01-01

    This paper discusses about the diagnosis and evaluation of brain higher functions, feature of their impairment induced by radiotherapy for brain tumor, and association of the impairment and neurogenesis in hippocampus (H). Radiation is one of important causes of cognitive impairment in patients with brain tumor: exempli gratia (e.g.) single irradiation of 2 Gy increases its risk. The impairment is usually diagnosed and evaluated with neuropsychological tests like mini-mental state examination (MMSE), authors' Ryudai version of the brief neuropsychological test battery, etc. The neurotoxicity of radiation is classified in acute effect caused by destruction of the blood brain barrier (BBB) appearing within 2 weeks after irradiation, early-late one of demyelination as a result of BBB rupture within 1-6 months after radiotherapy and late-late effect accompanying serious symptoms like necrosis of irradiated region at later than a few months to several years. Lowered neurogenic function in H and invasion of microglia cells are observed in autopsy specimen of the irradiated brain, and single X-irradiation at 5 or 10 Gy is known to result in the arrest of neurogenesis in the mouse H dentate gyrus. Lowered cognition by irradiation of H in clinical cases is particularly reported in children. Inflammatory biomarkers like cytokines are detected in the serum of irradiated patients as well as of animals. Although fMRI alone is not satisfactory to diagnose and evaluate the radiation-induced impairment, the imaging reveals the association of anatomically different regions in cognition through neural network. It has been recently shown that the impairment can be partially protected by planning the irradiation field so as to avoid H, by medication with donepezil, memantine, erythropoietin and indomethacin, and by hyperbaric oxygen therapy. (T.T.)

  20. The "Test Your Memory" test performs better than the MMSE in a population without known cognitive dysfunction

    NARCIS (Netherlands)

    Koekkoek, P.S.; Rutten, G.E.H.M.; Van den Berg, E.; van Sonsbeek, S.; Gorter, K.J.; Kappelle, L.J.; Biessels, G.J.

    2013-01-01

    1. Introduction Brief cognitive tests are increasingly implemented in both clinical and research settings. They are not only used for early recognition of cognitive deficits and dementia [1], but also for measuring differences in cognitive functioning between groups, for assessment of treatment

  1. Memory deficits in long-term survivors of childhood brain tumors may primarily reflect general cognitive dysfunctions

    DEFF Research Database (Denmark)

    Reimers, Tonny Solveig; Mortensen, Erik Lykke; Schmiegelow, Kjeld

    2007-01-01

    To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction.......To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction....

  2. Poly(adenosine 5'-diphosphate) ribose polymerase activation as a cause of metabolic dysfunction in critical illness.

    Science.gov (United States)

    Liaudet, Lucas

    2002-03-01

    Poly(adenosine 5'-diphosphate) ribose polymerase is a nuclear enzyme activated in response to genotoxic stress induced by a variety of DNA damaging agents. Several oxygen and nitrogen-centered free radicals, notably peroxynitrite, are strong inducers of DNA damage and poly(adenosine 5'-diphosphate) ribose polymerase activation in vitro and in vivo. Activation of this nuclear enzyme depletes the intracellular stores of its substrate nicotinamide adenine dinucleotide, slowing the rate of glycolysis, mitochondrial electron transport and adenosine triphosphate formation. This process triggers a severe energetic crisis within the cell, leading to acute cell dysfunction and cell necrosis. Poly(adenosine 5'-diphosphate) ribose polymerase also plays an important role in the regulation of inflammatory cascades, through a functional association with various transcription factors and transcription co-activators. Recent works identified this enzyme as a critical mediator of cellular metabolic dysfunction, inflammatory injury, and organ damage in conditions associated with overwhelming oxidative stress, including systemic inflammation, circulatory shock, and ischemia-reperfusion. Accordingly, pharmacological inhibitors of poly(adenosine 5'-diphosphate) ribose polymerase protect against cell death and tissue injury in such conditions, and may therefore represent novel therapeutic tools to limit multiple organ damage and dysfunction in critically ill patients.

  3. Hyperglycaemia in pregnant rats causes sex-related vascular dysfunction in adult offspring: role of cyclooxygenase-2.

    Science.gov (United States)

    de Sá, Francine Gomes; de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; da Silva, Odair Alves; Moreira, Hicla Stefany; Leal, Geórgia Andrade; da Rocha, Marcelo Aurélio; Duarte, Gloria Pinto; Xavier, Fabiano Elias

    2017-08-01

    What is the central question of this study? Hyperglycaemia during pregnancy induces vascular dysfunction and hypertension in male offspring. Given that female offspring from other fetal programming models are protected from the effects of fetal insult, the present study investigated whether there are sex differences in blood pressure and vascular function in hyperglycaemia-programmed offspring. What is the main finding and its importance? We demonstrated that hyperglycaemia in pregnant rats induced vascular dysfunction and hypertension only in male offspring. We found sex differences in oxidative stress and cyclooxygenase-2-derived prostanoid production that might underlie the vascular dysfunction. These differences, particularly in resistance arteries, may in part explain the absence of hypertension in female offspring born to hyperglycaemic dams. Exposure to maternal hyperglycaemia induces hypertension and vascular dysfunction in adult male offspring. Given that female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analysed possible differences relative to sex in blood pressure and vascular function in hyperglycaemia-programmed offspring. Hyperglycaemia was induced on day 7 of gestation (streptozotocin, 50 mg kg -1 ). Blood pressure, acetylcholine and phenylephrine or noradrenaline responses were analysed in the aorta and mesenteric resistance arteries of 3-, 6- and 12-month-old male and female offspring. Thromboxane A 2 release was analysed with commercial kits and superoxide anion (O 2 - ) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had higher blood pressure than control animals (O-CR). Contraction in response to phenylephrine increased and relaxation in response to acetylcholine decreased only in the aorta from 12-month-old male O-DR and not in age-matched O-CR. Contractile and vasodilator responses were preserved in both the

  4. Does Duloxetine Improve Cognitive Function Independently of Its Antidepressant Effect in Patients with Major Depressive Disorder and Subjective Reports of Cognitive Dysfunction?

    Directory of Open Access Journals (Sweden)

    Tracy L. Greer

    2014-01-01

    Full Text Available Introduction. Cognitive deficits are commonly reported by patients with major depressive disorder (MDD. Duloxetine, a dual serotonin/noradrenaline reuptake inhibitor, may improve cognitive deficits in MDD. It is unclear if cognitive improvements occur independently of antidepressant effects with standard antidepressant medications. Methods. Thirty participants with MDD who endorsed cognitive deficits at screening received 12-week duloxetine treatment. Twenty-one participants completed treatment and baseline and posttreatment cognitive testing. The Cambridge Neuropsychological Test Automated Battery was used to assess the following cognitive domains: attention, visual memory, executive function/set shifting and working memory, executive function/spatial planning, decision making and response control, and verbal learning and memory. Results. Completers showed significant cognitive improvements across several domains on tasks assessing psychomotor function and mental processing speed, with additional improvements in visual and verbal learning and memory, and affective decision making and response control. Overall significance tests for executive function tasks were also significant, although individual tasks were not, perhaps due to the small sample size. Most notably, cognitive improvements were observed independently of symptom reduction on all domains except verbal learning and memory. Conclusions. Patients reporting baseline cognitive deficits achieved cognitive improvements with duloxetine treatment, most of which were independent of symptomatic improvement. This trial is registered with NCT00933439.

  5. Lateral column lengthening for acquired adult flatfoot deformity caused by posterior tibial tendon dysfunction stage II: a retrospective comparison of calcaneus osteotomy with calcaneocuboid distraction arthrodesis.

    Science.gov (United States)

    Haeseker, Guus A; Mureau, Marc A; Faber, Frank W M

    2010-01-01

    In this study, clinical and radiological results after lateral column lengthening by calcaneocuboid distraction arthrodesis and calcaneus osteotomy were compared. Thirty-three patients (35 feet) treated with lateral column lengthening by distraction arthrodesis (14 patients, 16 feet; group I) or by calcaneus osteotomy (19 patients, 19 feet; group II) for adult-acquired flatfoot deformity caused by stage II posterior tibial tendon dysfunction were compared retrospectively. Mean follow-up was 42.4 months (range, 6-78 months) for group I and 15.8 months (range, 6-32 months) for group II (P lengthening by means of calcaneus osteotomy rather than distraction arthrodesis of the calcaneocuboid joint, for correction of stage II posterior tibial tendon dysfunction. Copyright 2010 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

    Science.gov (United States)

    Schäfer, C N; Guldager, H; Jørgensen, H L

    2011-01-01

    A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline

    Directory of Open Access Journals (Sweden)

    Awadh Kishor Pandit

    2013-01-01

    Full Text Available Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE, epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI, cerebrospinal-fluid analysis (CSF, and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor′s information were noted. Results: There were 15 (males = 10 patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years. The most common onset was subacute (64% and four (29% patients presented as SE. Predominant clinical presentations were seizures (100% almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40% it was normal, six (40% showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%, voltage-gated potassium channel antibody in five (36%, two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67% cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis.

  8. Garcinia kola seeds may prevent cognitive and motor dysfunctions in a type 1 diabetes mellitus rat model partly by mitigating neuroinflammation.

    Science.gov (United States)

    Seke Etet, Paul F; Farahna, Mohammed; Satti, Gwiria M H; Bushara, Yahia M; El-Tahir, Ahmed; Hamza, Muaawia A; Osman, Sayed Y; Dibia, Ambrose C; Vecchio, Lorella

    2017-04-15

    Background We reported recently that extracts of seeds of Garcinia kola, a plant with established hypoglycemic properties, prevented the loss of inflammation-sensible neuronal populations like Purkinje cells in a rat model of type 1 diabetes mellitus (T1DM). Here, we assessed G. kola extract ability to prevent the early cognitive and motor dysfunctions observed in this model. Methods Rats made diabetic by single injection of streptozotocin were treated daily with either vehicle solution (diabetic control group), insulin, or G. kola extract from the first to the 6th week post-injection. Then, cognitive and motor functions were assessed using holeboard and vertical pole behavioral tests, and animals were sacrificed. Brains were dissected out, cut, and processed for Nissl staining and immunohistochemistry. Results Hyperglycemia (209.26 %), body weight loss (-12.37 %), and T1DM-like cognitive and motor dysfunctions revealed behavioral tests in diabetic control animals were not observed in insulin and extract-treated animals. Similar, expressions of inflammation markers tumor necrosis factor (TNF), iba1 (CD68), and Glial fibrillary acidic protein (GFAP), as well as decreases of neuronal density in regions involved in cognitive and motor functions (-49.56 % motor cortex, -33.24 % medial septal nucleus, -41.8 % /-37.34 % cerebellar Purkinje /granular cell layers) were observed in diabetic controls but not in animals treated with insulin or G. kola. Conclusions Our results indicate that T1DM-like functional alterations are mediated, at least partly, by neuroinflammation and neuronal loss in this model. The prevention of the development of such alterations by early treatment with G. kola confirms the neuroprotective properties of the plant and warrant further mechanistic studies, considering the potential for human disease.

  9. Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2018-07-01

    Full Text Available Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region. Mechanistically, we demonstrated the disruptions of mitochondrial homeostasis and redox balance typically characterized by the disordered mitochondrial dynamics, mitophagy and glutathione redox couple, which is closely associated with the inhibitions of PINK1 and NRF2 signaling pathway as the key regulators of molecular responses in the context of neurotoxicity and neurodegenerative disorders. Most importantly, we found that administration with melatonin as a mitochondria-targeted antioxidant promoted the PINK1 accumulation on the mitochondrial membrane, and augmented the NRF2 accumulation and translocation. Moreover, melatonin pronouncedly enhanced the molecular interplay between NRF2 and PINK1. Furthermore, in the mouse hippocampal neuronal cells, overexpression of NRF2/PINK1 strikingly protected the hippocampal neurons from carbon ion-elicited toxic insults. Thus, these data suggest that alleviation of the sustained mitochondrial dysfunction and oxidative stress through co-modulation of NRF2 and PINK1 may be in charge of restoration of the cognitive

  10. Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of reversible cognitive impairment

    Directory of Open Access Journals (Sweden)

    Robert Dobbin Chow

    2012-04-01

    Full Text Available We herewith describe a patient with acute confusion, expressive aphasia and generalized seizures. A through workup excluded most causes of encephalopathy. He was, however, found to have TSH = 18.6 MIU/ml, T3reverse = 0.44nmol/L, T4 = 0.8ng/dl and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the patient was diagnosed with Hashimoto's encephalopathy and his mental status showed dramatic improvement (MMS 30/30 with high dose prednisone. Hashimoto's encephalopathy is rare disorder of presumed autoimmune origin characterized by cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti-Thyroid-Peroxidase AB, and a positive response to steroids.

  11. Signal pathway of hippocampal apoptosis and cognitive impairment of mice caused by cerium chloride.

    Science.gov (United States)

    Cheng, Zhe; Li, Na; Cheng, Jie; Hu, Renping; Gao, Guodong; Cui, Yaling; Gong, Xiaolan; Wang, Ling; Hong, Fashui

    2012-12-01

    Experimental studies have demonstrated that lanthanides could impair cognitive functions of children and animals, but very little is known about the hippocampal apoptosis and its molecular mechanism. The study investigated the signal pathway of hippocampal apoptosis induced by intragastric administration of CeCl(3) for 60 consecutive days. It showed that cerium had been significantly accumulated in the mouse hippocampus, and CeCl(3) caused hippocampal apoptosis and impairment of spatial recognition memory of mice. CeCl(3) effectively activated caspase-3 and -9, inhibited Bcl-2, and increased the levels of Bax and cytochrome c, promoted accumulation of reactive oxygen species in the mouse hippocampus. It implied that CeCl(3)-induced apoptosis in the mouse hippocampus could be triggered via mitochondrion-mediated pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers. 2011 Wiley Periodicals, Inc

  12. Long-term smoking causes more advanced coronary endothelial dysfunction in middle-aged smokers compared to young smokers

    International Nuclear Information System (INIS)

    Naya, Masanao; Goto, Daisuke; Tsutsui, Hiroyuki; Morita, Koichi; Manabe, Osamu; Hirata, Kenji; Tamaki, Nagara; Yoshinaga, Keiichiro; Katoh, Chietsugu

    2011-01-01

    Smoking cessation has been shown to normalize the coronary endothelial dysfunction in healthy young smokers. However, its effect has not been explored in middle-aged smokers with a longer history of smoking. Therefore, we compared the effects of smoking cessation on coronary vasomotor response between both young and middle-aged smokers and identified the predictor for its improvement. This study investigated 14 young healthy smokers (age 25.2 ± 2.3 years), 13 middle-aged smokers (age 42.0 ± 6.5 years) and 10 non-smokers. Myocardial blood flow (MBF) was measured by using 15 O-water positron emission tomography (PET). At baseline, the ratio of MBF during the cold pressor test (CPT) to that at rest (MBF CPT/rest ), the index of coronary endothelial function, was significantly decreased in both young and middle-aged smokers compared to non-smokers (1.24 ± 0.20 and 1.10 ± 0.39 vs 1.53 ± 0.18, p CPT/rest at 1 month after smoking cessation significantly increased in young smokers, but not in middle-aged smokers. By multivariate analysis, baseline serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) was an independent predictor for the changes in MBF CPT/rest after smoking cessation (β = -0.45, p < 0.05). Coronary endothelial dysfunction was reversible by short-term smoking cessation in young smokers, but not in middle-aged smokers, which was associated with serum MDA-LDL levels. Long-term smoking exposure could lead to more advanced coronary endothelial dysfunction and atherosclerosis possibly via oxidative stress. (orig.)

  13. Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice.

    Science.gov (United States)

    Gulati, Puja; Muthuraman, Arunachalam; Kaur, Parneet

    2015-04-01

    The present study was designed to investigate the role of flunarizine (a non-selective calcium channel blocker) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice. Bilateral carotid artery occlusion of 12min followed by reperfusion for 24h was given to induce cerebral injury in male Swiss mice. The assessment of learning & memory was performed by Morris water maze test; motor in-coordination was evaluated by rota rod, lateral push and inclined beam walking tests; cerebral infarct size was quantified by triphenyltetrazolium chloride staining. In addition, reduced glutathione (GSH), total calcium and acetylcholinesterase (AChE) activity were also estimated in aged brain tissue. Donepezil treated group served as a positive control in this study. Ischemia reperfusion (I/R) injury produced significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Further, I/R injury also produced significant increase in levels of total calcium, AChE activity and decrease in GSH levels. Pretreatment of flunarizine significantly attenuated I/R induced infarct size, behavioral and biochemical changes. Hence, it may be concluded that, a non-selective calcium channel blocker can be useful in I/R associated cognitive dysfunction due to its anti-oxidant, anti-infarct and modulatory actions of neurotransmitters & calcium channels. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. [Correlations of plasma concentrations of β-amyloid peptide and S-100β with postoperative cognitive dysfunction in patients undergoing oral and maxillofacial cancer surgery].

    Science.gov (United States)

    Liang, Bing; Sun, Yuan-Qing; Jiang, Jue; Xu, Hui

    2016-12-01

    To evaluate the changes of perioperative plasma concentrations of Aβ 1-40 and S-100β to determine the relationship with postoperative cognitive dysfunction in elderly patients undergoing oral and maxillofacial cancer surgeries. One hundred and fifteen patients aged at least 60 years undergoing oral and maxillofacial tumor resection were investigated between May 2014 to December 2014.Neuropsychological tests for detecting postoperative cognitive dysfunction(POCD) were performed one day before surgery and 7 days postoperatively. According to the results of neuropsychological tests on day 7, patients were divided into POCD group and non-POCD group.Plasma values of Aβ 1-40 and S-100β were determined with enzyme linked immunosorbent assay (ELISA) before anesthesia induction, 24 h and 7 days after surgery. The data were analyzed using SPSS 19.0 software package. According to the definition, POCD was present in 37 of 115 (32.3%) patients 1 week after surgery. Compared with pre-anesthesia, S-100β levels in POCD group were significantly increased (Psurgery (Poral and maxillofacial surgeries with general anesthesia. The increasing levels of Aβ 1-40 , S-100β may be associated with the occurence of POCD. Patients with long-lasting operation and high concentrations of Aβ 1-40 and S-100β after surgeries were at a higher risk of POCD. The clinical values of Aβ 1-40 and S-100 as predictive measurements of POCD after oral and maxillofacial cancer surgery appear to be reasonable.

  15. Effect of Integrated Cognitive Therapy on Hippocampal Functional Connectivity Patterns in Stroke Patients with Cognitive Dysfunction: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Shanli Yang

    2014-01-01

    Full Text Available Objective. This study aimed to identify abnormal hippocampal functional connectivity (FC following ischemic stroke using resting-state fMRI. We also explored whether abnormal hippocampal FC could be modulated by integrated cognitive therapy and tested whether these alterations were associated with cognitive performance. Methods. 18 right-handed cognitively impaired ischemic stroke patients and 18 healty control (HC subjects were included in this study. Stroke subjects were scanned at baseline and after integrated cognitive therapy, while HCs were only scanned at baseline, to identify regions that show significant correlations with the seed region. Behavioral and cognitive assessments were obtained before each scan. Results. During the resting state, we found abnormal hippocampal FC associated with temporal regions, insular cortex, cerebellum, and prefrontal cortex in stroke patients compared to HCs. After integrated cognitive therapy, however, the stroke group showed increased hippocampal FC mainly located in the prefrontal gyrus and the default mode network (DMN. Altered hippocampal FC was associated with cognitive improvement. Conclusion. Resting-state fMRI may provide novel insight into the study of functional networks in the brain after stroke. Furthermore, altered hippocampal FC may be a compensatory mechanism for cognitive recovery after ischemic stroke.

  16. Autonomic dysfunction in mild cognitive impairment: evidence from power spectral analysis of heart rate variability in a cross-sectional case-control study.

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    Paola Nicolini

    Full Text Available Mild cognitive impairment (MCI is set to become a major health problem with the exponential ageing of the world's population. The association between MCI and autonomic dysfunction, supported by indirect evidence and rich with clinical implications in terms of progression to dementia and increased risk of mortality and falls, has never been specifically demonstrated.To conduct a comprehensive assessment of autonomic function in subjects with MCI by means of power spectral analysis (PSA of heart rate variability (HRV at rest and during provocative manoeuvres.This cross-sectional study involved 80 older outpatients (aged ≥ 65 consecutively referred to a geriatric unit and diagnosed with MCI or normal cognition (controls based on neuropsychological testing. PSA was performed on 5-minute electrocardiographic recordings under three conditions--supine rest with free breathing (baseline, supine rest with paced breathing at 12 breaths/minute (parasympathetic stimulation, and active standing (orthosympathetic stimulation--with particular focus on the changes from baseline to stimulation of indices of sympathovagal balance: normalized low frequency (LFn and high frequency (HFn powers and the LF/HF ratio. Blood pressure (BP was measured at baseline and during standing. Given its exploratory nature in a clinical population the study included subjects on medications with a potential to affect HRV.There were no significant differences in HRV indices between the two groups at baseline. MCI subjects exhibited smaller physiological changes in all three HRV indices during active standing, consistently with a dysfunction of the orthosympathetic system. Systolic BP after 10 minutes of standing was lower in MCI subjects, suggesting dysautonomia-related orthostatic BP dysregulation.Our study is novel in providing evidence of autonomic dysfunction in MCI. This is associated with orthostatic BP dysregulation and the ongoing follow-up of the study population will

  17. Perioperative management in order to minimise postoperative delirium and postoperative cognitive dysfunction: Results from a Swedish web-based survey

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    Pether K. Jildenstål

    2014-09-01

    Conclusion: Swedish anaesthesia personnel are concerned about the risk of postoperative cognitive side-effects but are more concerned about cardiovascular/pulmonary risks, pain, PONV and the rare event of awareness. Most respondents were not convinced about the use of depth-of-anaesthesia monitors. There is a need to improve knowledge around risk factors, prevention and management of postoperative cognitive side effects.

  18. There Is No Association Between the Circadian Clock Gene HPER3 and Cognitive Dysfunction After Noncardiac Surgery

    DEFF Research Database (Denmark)

    Voigt Hansen, Melissa; Simon Rasmussen, Lars; Jespersgaard, Cathrine

    2012-01-01

    The specific clock-gene PERIOD3 is important with regard to circadian rhythmicity, sleep homeostasis, and cognitive function. The allele PER3(5/5) has been associated with worse cognitive performance in response to sleep deprivation. We hypothesized that patients with the PER3(5/5) genotype would...

  19. Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction.

    Directory of Open Access Journals (Sweden)

    Hiroe Tabara

    Full Text Available Gefitinib (Iressa is an inhibitor of the epidermal growth factor receptor (EGFR that has shown promising activity in the treatment of patients with non-small cell lung cancer (NSCLC. However, adverse side effects of gefitinib treatment, such as respiratory dysfunction, have limited the therapeutic benefit of this targeting strategy. The present results show that this adverse effect can be attributed to the inhibition of the novel gefitinib target GAK (Cyclin G-associated kinase, which is as potently inhibited by the drug as the tyrosine kinase activity of EGFR. Knockout mice expressing the kinase-dead form of GAK (GAK-kd died within 30 min after birth primarily due to respiratory dysfunction. Immunohistochemical analysis revealed that surfactant protein A (SP-A was abundant within alveolar spaces in GAK-kd(+/+ mice but not in GAK-kd(-/- pups. E-cadherin and phosphorylated EGFR signals were also abnormal, suggesting the presence of flat alveolar cells with thin junctions. These results suggest that inhibition of GAK by gefitinib may cause pulmonary alveolar dysfunction, and the present study may help prevent side effects associated with gefitinib therapy in NSCLC patients.

  20. Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment and dysfunction in central nervous system: the potential roles played by microglia

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    Yang Q

    2013-08-01

    Full Text Available Qingchan Yang,1,* Yan Wang,2,* Jing Feng,2 Jie Cao,2 Baoyuan Chen2 1Graduate School of Tianjin Medical University, 2Respiratory Department, Tianjin Medical University General Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Abstract: Obstructive sleep apnea (OSA is a common condition characterized by repetitive episodes of complete (apnea or partial (hypopnea obstruction of the upper airway during sleep, resulting in oxygen desaturation and arousal from sleep. Intermittent hypoxia (IH resulting from OSA may cause structural neuron damage and dysfunction in the central nervous system (CNS. Clinically, it manifests as neurocognitive and behavioral deficits with oxidative stress and inflammatory impairment as its pathophysiological basis, which are mediated by microglia at the cellular level. Microglia are dominant proinflammatory cells in the CNS. They induce CNS oxidative stress and inflammation, mainly through mitochondria, reduced nicotinamide adenine dinucleotide phosphate oxidase, and the release of excitatory toxic neurotransmitters. The balance between neurotoxic versus protective and anti- versus proinflammatory microglial factors might determine the final roles of microglia after IH exposure from OSA. Microglia inflammatory impairments will continue and cascade persistently upon activation, ultimately resulting in clinically significant neuron damage and dysfunction in the CNS. In this review article, we summarize the mechanisms of structural neuron damage in the CNS and its concomitant dysfunction due to IH from OSA, and the potential roles played by microglia in this process. Keywords: intermittent hypoxia, obstructive sleep apnea, microglia, inflammation, apoptosis

  1. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    Science.gov (United States)

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The Broader Cognitive Phenotype of Autism in Parents: How Specific Is the Tendency for Local Processing and Executive Dysfunction?

    Science.gov (United States)

    Bolte, Sven; Poustka, Fritz

    2006-01-01

    Background: The objective of this study was to investigate the tendency for local processing style ("weak central coherence") and executive dysfunction in parents of subjects with an autism spectrum disorder (ASD) compared with parents of individuals with early onset schizophrenia (EOS) and mental retardation (MR). Method: Sixty-two…

  3. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition

    Science.gov (United States)

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17–88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  4. Examining Age-Related Shared Variance Between Face Cognition, Vision, and Self-Reported Physical Health: A Test of the Common Cause Hypothesis for Social Cognition

    Directory of Open Access Journals (Sweden)

    Sally eOlderbak

    2015-08-01

    Full Text Available The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing, and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain. We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities, specifically face perception and face memory. Based on a sample of 443 adults (17 to 88 years old, we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident.

  5. Long-term smoking causes more advanced coronary endothelial dysfunction in middle-aged smokers compared to young smokers

    Energy Technology Data Exchange (ETDEWEB)

    Naya, Masanao; Goto, Daisuke; Tsutsui, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Cardiovascular Medicine, Sapporo (Japan); Morita, Koichi; Manabe, Osamu; Hirata, Kenji; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Yoshinaga, Keiichiro [Hokkaido University Graduate School of Medicine, Department of Molecular Imaging, Sapporo (Japan); Katoh, Chietsugu [Hokkaido University Graduate School of Medicine, Department of Health Science, Sapporo (Japan)

    2011-03-15

    Smoking cessation has been shown to normalize the coronary endothelial dysfunction in healthy young smokers. However, its effect has not been explored in middle-aged smokers with a longer history of smoking. Therefore, we compared the effects of smoking cessation on coronary vasomotor response between both young and middle-aged smokers and identified the predictor for its improvement. This study investigated 14 young healthy smokers (age 25.2 {+-} 2.3 years), 13 middle-aged smokers (age 42.0 {+-} 6.5 years) and 10 non-smokers. Myocardial blood flow (MBF) was measured by using {sup 15}O-water positron emission tomography (PET). At baseline, the ratio of MBF during the cold pressor test (CPT) to that at rest (MBF{sub CPT/rest}), the index of coronary endothelial function, was significantly decreased in both young and middle-aged smokers compared to non-smokers (1.24 {+-} 0.20 and 1.10 {+-} 0.39 vs 1.53 {+-} 0.18, p < 0.05 and p < 0.001, respectively). The ratio of MBF during adenosine triphosphate infusion to that at rest was significantly decreased in middle-aged smokers compared to young smokers and non-smokers (3.34 {+-} 1.52 vs 4.43 {+-} 0.92 and 4.69 {+-} 1.25, p < 0.05, respectively). MBF{sub CPT/rest} at 1 month after smoking cessation significantly increased in young smokers, but not in middle-aged smokers. By multivariate analysis, baseline serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) was an independent predictor for the changes in MBF{sub CPT/rest} after smoking cessation ({beta} = -0.45, p < 0.05). Coronary endothelial dysfunction was reversible by short-term smoking cessation in young smokers, but not in middle-aged smokers, which was associated with serum MDA-LDL levels. Long-term smoking exposure could lead to more advanced coronary endothelial dysfunction and atherosclerosis possibly via oxidative stress. (orig.)

  6. [Social dysfunction in schizotypy].

    Science.gov (United States)

    de Wachter, O; De La Asuncion, J; Sabbe, B; Morrens, M

    2016-01-01

    Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. To describe schizotypy and its influence on social functioning. We reviewed the literature systematically using the online databases PubMed and PsycINFO. The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia.

  7. Radiation-induced neurobehavioral dysfunctions

    International Nuclear Information System (INIS)

    Manda, Kailash

    2013-01-01

    There is a lacuna between sparsely reported immediate effects and the well documented delayed effects on cognitive functions seen after ionizing radiation exposure. We reported the radiation-dose dependent incongruity in the early cognitive changes and its correlation with the structural aberration as reported by imaging study. The delayed effect of radiation was investigated to understand the role of hippocampal neurogenesis in the functional recovery of cognition. C57BL/6 mice were exposed to different doses of γ-radiation and 24 hrs after exposure, t