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Sample records for cognitive dysfunction caused

  1. Rehabilitation for a Patient with Hemiplegia, Ataxia, and Cognitive Dysfunction Caused by Pontine Hemorrhage

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsunoda

    2015-10-01

    Full Text Available Patients with pontine hemorrhage usually experience severe disturbances of consciousness, pupillary abnormalities, quadriparesis, and respiratory failure. However, little is known regarding cognitive dysfunction in patients with pontine hemorrhage. We report the case of a rehabilitation patient presenting with hemiplegia, ataxia, and cognitive dysfunction caused by a pontine hemorrhage. A 55-year-old, right-handed male suffered sudden onset of vertigo, dysarthria, and hemiplegia on the right side. He was diagnosed with brain stem hemorrhage, and conservative treatment was administered. The vertigo improved, but dysarthria, ataxia, hemiplegia, and gait disorder persisted. He was disoriented with respect to time and place and showed a poor attention span, impaired executive function, and reduced volition. A computed tomography revealed hematomas across the pons on both sides, but no lesions were obvious in the cerebellum and cerebrum. Single-photon emission tomography showed decreased perfusion in the brain stem, bilateral basal ganglia, and frontal and parietal lobes in the left hemisphere. The patient received exercise therapy and cognitive rehabilitation, and home modifications were performed to allow him to continue living at home under the supervision of his family. His symptoms improved, along with enhanced regional cerebral blood flow to the frontal and temporal lobes. These findings suggest that the pontine hemorrhage caused diaschisis resulting in secondary reduction of activity in the cerebral hemisphere and the occurrence of cortical symptoms. Therefore, rehabilitation is necessary, along with active instructions for the family members of patients with severe neurological deficits.

  2. Rehabilitation for a Patient with Hemiplegia, Ataxia, and Cognitive Dysfunction Caused by Pontine Hemorrhage.

    Science.gov (United States)

    Tsunoda, Tetsuya; Maeshima, Shinichiro; Watanabe, Makoto; Nagai, Ayako; Ueno, Yoshiya; Ozeki, Yasunori; Okamoto, Sayaka; Mizuno, Shiho; Sonoda, Shigeru

    2015-01-01

    Patients with pontine hemorrhage usually experience severe disturbances of consciousness, pupillary abnormalities, quadriparesis, and respiratory failure. However, little is known regarding cognitive dysfunction in patients with pontine hemorrhage. We report the case of a rehabilitation patient presenting with hemiplegia, ataxia, and cognitive dysfunction caused by a pontine hemorrhage. A 55-year-old, right-handed male suffered sudden onset of vertigo, dysarthria, and hemiplegia on the right side. He was diagnosed with brain stem hemorrhage, and conservative treatment was administered. The vertigo improved, but dysarthria, ataxia, hemiplegia, and gait disorder persisted. He was disoriented with respect to time and place and showed a poor attention span, impaired executive function, and reduced volition. A computed tomography revealed hematomas across the pons on both sides, but no lesions were obvious in the cerebellum and cerebrum. Single-photon emission tomography showed decreased perfusion in the brain stem, bilateral basal ganglia, and frontal and parietal lobes in the left hemisphere. The patient received exercise therapy and cognitive rehabilitation, and home modifications were performed to allow him to continue living at home under the supervision of his family. His symptoms improved, along with enhanced regional cerebral blood flow to the frontal and temporal lobes. These findings suggest that the pontine hemorrhage caused diaschisis resulting in secondary reduction of activity in the cerebral hemisphere and the occurrence of cortical symptoms. Therefore, rehabilitation is necessary, along with active instructions for the family members of patients with severe neurological deficits.

  3. Intermittent hypoxia caused cognitive dysfunction relate to miRNAs dysregulation in hippocampus.

    Science.gov (United States)

    Gao, Huabin; Han, Zhaoli; Huang, Shan; Bai, Ruojing; Ge, Xintong; Chen, Fanglian; Lei, Ping

    2017-09-29

    Intermittent hypoxia (IH) is a characteristic pathophysiological change of obstructive sleep apnea (OSA), a commonly diagnosed chronic sleep disorder. With the process of OSA, patients will suffer from the nervous system damage and appear to multiple cognitive dysfunction. The mechanism that how IH causes cognitive impairment is still unknown. Both control and experimental rats were placed in conditions absence and presence of intermittent hypoxia (IH) for 8h a day for a week, two weeks and four weeks, and then followed by behavioral assessments with Morris Water Maze (MWM) test. The results showed that the escape latency of the tested animals to IH significantly increased the escape latency on the last four training days in comparison to the control group. Consistent with this, the expressions of apoptosis/anti-apoptosis proteins were both changed in the hippocampus. Then we utilized the miRNA microarray assay to investigate the level of miRNA expression in rat hippocampus which suffered from intermittent hypoxia. It is noteworthy that the expressions of miR-26b and miR-207 were consistently dysregulated in all the experimental groups post IH. And we utilized qRT-PCR methods to verify the microarray results. Our results showed that microarray based analysis of microRNA expression in rat hippocampus after IH has shown that some microRNAs such as miR-26b and miR-207 could be involved in the OSA-induced cognitive impairments. Copyright © 2017. Published by Elsevier B.V.

  4. Stem cell transplantation strategies for the restoration of cognitive dysfunction caused by cranial radiotherapy.

    Science.gov (United States)

    Acharya, Munjal M; Roa, Dante E; Bosch, Omar; Lan, Mary L; Limoli, Charles L

    2011-10-18

    Radiotherapy often provides the only clinical recourse for those afflicted with primary or metastatic brain tumors. While beneficial, cranial irradiation can induce a progressive and debilitating decline in cognition that may, in part, be caused by the depletion of neural stem cells. Given the increased survival of patients diagnosed with brain cancer, quality of life in terms of cognitive health has become an increasing concern, especially in the absence of any satisfactory long-term treatments. To address this serious health concern we have used stem cell replacement as a strategy to combat radiation-induced cognitive decline. Our model utilizes athymic nude rats subjected to cranial irradiation. The ionizing radiation is delivered as either whole brain or as a highly focused beam to the hippocampus via linear accelerator (LINAC) based stereotaxic radiosurgery. Two days following irradiation, human neural stem cells (hNSCs) were stereotaxically transplanted into the hippocampus. Rats were then assessed for changes in cognition, grafted cell survival and for the expression of differentiation-specific markers 1 and 4-months after irradiation. Our cognitive testing paradigms have demonstrated that animals engrafted with hNSCs exhibit significant improvements in cognitive function. Unbiased stereology reveals significant survival (10-40%) of the engrafted cells at 1 and 4-months after transplantation, dependent on the amount and type of cells grafted. Engrafted cells migrate extensively, differentiate along glial and neuronal lineages, and express a range of immature and mature phenotypic markers. Our data demonstrate direct cognitive benefits derived from engrafted human stem cells, suggesting that this procedure may one day afford a promising strategy for the long-term functional restoration of cognition in individuals subjected to cranial radiotherapy. To promote the dissemination of the critical procedures necessary to replicate and extend our studies, we have

  5. 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...

  6. 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...... 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....

  7. Motor-Coordinative and Cognitive Dysfunction Caused by Mutant TDP-43 Could Be Reversed by Inhibiting Its Mitochondrial Localization.

    Science.gov (United States)

    Wang, Wenzhang; Arakawa, Hiroyuki; Wang, Luwen; Okolo, Ogoegbunam; Siedlak, Sandra L; Jiang, Yinfei; Gao, Ju; Xie, Fei; Petersen, Robert B; Wang, Xinglong

    2017-01-04

    Dominant missense mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS), and the cytoplasmic accumulation of TDP-43 represents a pathological hallmark in ALS and frontotemporal lobar degeneration (FTD). Behavioral investigation of the transgenic mouse model expressing the disease-causing human TDP-43 M337V mutant (TDP-43(M337V) mice) is encumbered by premature death in homozygous transgenic mice and a reported lack of phenotype assessed by tail elevation and footprint in hemizygous transgenic mice. Here, using a battery of motor-coordinative and cognitive tests, we report robust motor-coordinative and cognitive deficits in hemizygous TDP-43(M337V) mice by 8 months of age. After 12 months of age, cortical neurons are significantly affected by the mild expression of mutant TDP-43, characterized by cytoplasmic TDP-43 mislocalization, mitochondrial dysfunction, and neuronal loss. Compared with age-matched non-transgenic mice, TDP-43(M337V) mice demonstrate a similar expression of total TDP-43 but higher levels of TDP-43 in mitochondria. Interestingly, a TDP-43 mitochondrial localization inhibitory peptide abolishes cytoplasmic TDP-43 accumulation, restores mitochondrial function, prevents neuronal loss, and alleviates motor-coordinative and cognitive deficits in adult hemizygous TDP-43(M337V) mice. Thus, this study suggests hemizygous TDP-43(M337V) mice as a useful animal model to study TDP-43 toxicity and further consolidates mitochondrial TDP-43 as a novel therapeutic target for TDP-43-linked neurodegenerative diseases. Published by Elsevier Inc.

  8. Cognitive dysfunction in spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Helio Afonso Ghizoni Teive

    Full Text Available Abstract Spinocerebellar ataxias (SCAs comprise a heterogeneous group of complex neurodegenerative diseases, characterized by the presence of progressive cerebellar ataxia, associated or otherwise with ophthalmoplegia, pyramidal signs, extrapyramidal features, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia. Objective: To verify the presence of cognitive dysfunction among the main types of SCA described in the literature. Methods: the review was conducted using the search system of the PUBMED and OMIM databases. Results: Cognitive dysfunction occurs in a considerable proportion of SCA, particularly in SCA 3, which is the most frequent form of SCA worldwide. Dementia has been described in several other types of SCA such as SCA 2, SCA 17 and DRPLA. Mental retardation is a specific clinical feature of SCA 13. Conclusions: The role of the cerebellum in cognitive functions has been observed in different types of SCAs which can manifest varying degrees of cognitive dysfunction, dementia and mental retardation.

  9. Toxicant Exposure and Bioaccumulation: A Common and Potentially Reversible Cause of Cognitive Dysfunction and Dementia

    Directory of Open Access Journals (Sweden)

    Stephen J. Genuis

    2015-01-01

    Full Text Available Juxtaposed alongside the ongoing rise in the incidence and prevalence of dementia, is the surge of recent research confirming widespread exposure and bioaccumulation of chemical toxicants. Evidence from sources such as the Centers for Disease Control reveals that most people have accrued varying degrees of assorted toxic pollutants including heavy metals, flame retardants, and pesticide residues within their bodies. It has been well established that many of these toxicants have neurodegenerative as well as neurodevelopmental impact as a result of various pathophysiologic mechanisms including neuronal mitochondrial toxicity and disruption of neurotransmitter regulation. Elimination of stockpiled toxicants from the body may diminish adverse toxicant impact on human biology and allow restoration of normal physiological function. Incorporating a review of medical literature on toxicant exposure and dementia with a case history of a lead-exposed individual diagnosed with dementia, this paper will discuss a much overlooked and potentially widespread cause of declining brain function and dementia.

  10. COGNITIVE DYSFUNCTIONS IN DIABETIC POLYNEUROPATHY

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    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.

  11. Cognitive dysfunction in senior pets.

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    Crowell-Davis, Sharon L

    2008-02-01

    Aging pets can experience declines in memory, learning, perception, and awareness. These pets may be disoriented, forget previously learned behaviors, develop new fears and anxiety, or change their interactions with people. When these changes are due to cognitive dysfunction, behavioral and environmental adjustments along with medical therapy can slow the progression and keep pets active longer.

  12. Cognitive Dysfunction in Fibromyalgia

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    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. [Cognitive dysfunction in fibromyalgia].

    Science.gov (United States)

    Gelonch, Olga; Garolera, Maite; Rosselló, Lluís; Pifarré, Josep

    2013-06-01

    Introduccion. Las personas diagnosticadas de fibromialgia refieren de manera muy frecuente quejas sobre su pobre funcionamiento cognitivo. En los ultimos anos ha aumentado el interes para investigar cuales son las alteraciones cognitivas presentes en esta enfermedad. Objetivo. Realizar una revision de las investigaciones publicadas sobre fibromialgia y funciones cognitivas. Desarrollo. Se realizo una busqueda bibliografica con un intervalo temporal desde 1995 hasta 2012. Los terminos de busqueda incluyeron las palabras clave 'fibromyalgia' y 'cognition', 'attention', 'memory', 'language', 'perception', 'executive functions' y 'disexecutive syndrome'. Se seleccionaron 64 registros tras aplicar criterios de inclusion. Conclusiones. Los estudios que han analizado las funciones cognitivas en las personas diagnosticadas de fibromialgia han sido escasos y mayoritariamente con muestras pequenas. Se han identificado deficits principalmente en la memoria de trabajo y en las capacidades atencionales mas complejas, donde el factor distraccion tiene una relevancia importante. Tambien se ha identificado deterioro en la memoria a largo plazo y en las funciones ejecutivas. Existe consenso entre los diversos estudios en que el grado de dolor tiene una relacion directa con el nivel de disfuncion cognitiva, mientras que no existe total consenso para explicar la influencia de la depresion y ansiedad sobre el funcionamiento cognitivo en estos pacientes.

  14. 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......, sleep deprivation, unfamiliar surroundings, and medication errors. Enhanced recovery programmes (fast-track regimens) may allow earlier discharge which is probably beneficial for the elderly. Frailty is becoming an increasingly important concept that needs to be clinically considered in elderly patients...

  15. Nutraceuticals, aging, and cognitive dysfunction.

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    Head, Elizabeth; Zicker, Steven C

    2004-01-01

    Decline in cognitive function that accompanies aging in dogs might have a biological basis, and many of the disorders associated with aging in canines might be preventable through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants might be one class of nutraceutical that benefits aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which can lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes might lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs; however, determining which compounds, combinations, dosage ranges, when to initiate intervention, and long-term effects constitute critical gaps in knowledge about this subject.

  16. Multiple system atrophy and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Sen-yang LANG

    2016-06-01

    Full Text Available As the survival of patients with multiple system atrophy (MSA is prolonged, patients may present cognitive dysfunction or even dementia in addition to autonomic dysfunction, damage of extrapyramidal system and cerebellar ataxia. This article made a brief summary on the research progress of MSA combined with cognitive dysfunction reported at home and abroad. DOI: 10.3969/j.issn.1672-6731.2016.06.003

  17. Modeling Cognitive Dysfunction in Neurofibromatosis-1

    OpenAIRE

    Diggs-Andrews, Kelly A.; David H Gutmann

    2013-01-01

    Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, Neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and mechanistically dissect the molecular and cellular bases underlying cognitive dysfunction. In this review, we ...

  18. Modeling cognitive dysfunction in neurofibromatosis-1.

    Science.gov (United States)

    Diggs-Andrews, Kelly A; Gutmann, David H

    2013-04-01

    Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and dissect mechanistically the molecular and cellular bases underlying cognitive dysfunction. In this review, we discuss Nf1 fly and mouse systems that mimic many of the cognitive abnormalities seen in children with NF1. Further, we describe discoveries from these models that have uncovered defects in the regulation of Ras activity, cAMP generation, and dopamine homeostasis as key mechanisms important for cognitive dysfunction in children with NF1.

  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. Neck pain causes respiratory dysfunction.

    Science.gov (United States)

    Kapreli, Eleni; Vourazanis, Evangelos; Strimpakos, Nikolaos

    2008-01-01

    This paper describes a presumptive mechanism for the development of changes in respiratory function due to chronic neck pain. The patient with neck pain presents a number of factors that could constitute a predisposition of leading to a respiratory dysfunction: (a) the decreased strength of deep neck flexors and extensors, (b) the hyperactivity and increased fatigability of superficial neck flexors, (c) the limitation of range of motion, (d) the decrease in proprioception and disturbances in neuromuscular control, (e) the existence of pain and (f) the psychosocial influence of dysfunction. The possible connection of neck pain and respiratory function could have a great impact on various clinical aspects notably patient assessment, rehabilitation and pharmacological prescription.

  1. Dissociation: Cognitive capacity or dysfunction?

    NARCIS (Netherlands)

    de Ruiter, M.B.; Bernet, M.; Phaf, R.H.

    2006-01-01

    Dissociative experiences are mostly studied as a risk factor for dissociative pathology. Nonpathological dissociation is quite common in the general population, however, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through the experience of

  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. Inherited Causes of Exocrine Pancreatic Dysfunction

    Directory of Open Access Journals (Sweden)

    Peter R Durie

    1997-01-01

    Full Text Available The exocrine pancreas is functionally immature at birth. Protease function is probably adequate, but lipase activity approximates 5% to 10% of adult values in the newborn and remains low in infancy. Pancreatic amylase secretion is essentially absent at birth and remains low through the first years of life. Functional disturbances of the exocrine pancreas are less frequent in childhood than in adult life. Causes of pancreatic dysfunction in childhood can be divided in two general categories: hereditary conditions, which directly affect the pancreas; and acquired disorders, in which loss of pancreatic function is a secondary phenomenon. Most inherited causes of pancreatic dysfunction are due to a generalized disorder. Cystic fibrosis is, by far, the most common inherited cause of disturbed pancreatic function among Caucasian children. All other inherited causes of exocrine pancreatic dysfunction (eg, Johanson-Blizzard syndrome are uncommon or rare.

  4. 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......). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative...... cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1-2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6-2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive...

  5. 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.

  6. Acute cognitive dysfunction after hip fracture

    DEFF Research Database (Denmark)

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

    2006-01-01

    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......, but also the number of peri-operative transfusions. The development of APOCD was also associated with impaired post-operative rehabilitation and an increased length of stay. APOCD was associated with the development of a major medical complication in 35% of all patients. In 65% of patients developing APOCD...

  7. 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…

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    OBJECTIVE: Hyperthyroidism has been suggested to adversely affect cognitive function. However, this association could also be caused by genetic and environmental factors affecting both the development of hyperthyroidism and cognitive functioning. By investigating twin pairs discordant...... for hyperthyroidism, this potential confounding can be minimized. The aim of the study was to examine if hyperthyroidism is associated with long-term cognitive dysfunction. DESIGN: Twin case-control study. PATIENTS: Twin pairs discordant for hyperthyroidism were identified by record-linkage between The Danish...... 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...

  9. Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice.

    Science.gov (United States)

    Qian, Xiao-Lan; Zhang, Wei; Liu, Ming-Zheng; Zhou, Yu-Bing; Zhang, Jing-Min; Han, Li; Peng, You-Mei; Jiang, Jin-hua; Wang, Qing-Duan

    2015-01-05

    Postoperative cognitive dysfunction (POCD) is a frequent complication following major surgery in the elderly. However, the exact pathogenic mechanisms are still unknown. Dexmedetomidine, a selective alpha 2 adrenal receptor agonist, was revealed anesthesia and brain protective role. The present study aimed to examine whether dexmedetomdine protects against POCD induced by major surgical trauma under general anesthesia in aged mice. In the present study, cognitive function was assessed by Y-maze. Proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), apoptosis-related factor caspase-3 and Bax were detected by real-time PCR, Western blot or immunohistochemistry. The results showed that anesthesia alone caused weak cognitive dysfunction on the first day after general anesthesia. Cognitive function in mice with splenectomy under general anesthesia was significantly exacerbated at the first and third days after surgery, and was significantly improved by dexmedetomidine administration. Splenectomy increased the expression of IL-1β, TNF-α, Bax and caspase-3 in hippocampus. These changes were significantly inversed by dexmedetomidine. These results suggest that hippocampal inflammatory response and neuronal apoptosis may contribute to POCD, and selective alpha 2 adrenal receptor excitation play a protective role.

  10. Iatrogenic causes of salivary gland dysfunction

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-02-01

    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. 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.

  12. Hashimoto's Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion.

    Science.gov (United States)

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-12-01

    Hashimoto's encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto's encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto's encephalopathy is very rare. We report a 65-year-old man who developed acute onset of cognitive decline and convulsion due to Hashimoto's encephalopathy.

  13. [Overview and assessment of cognitive function in interpreting postoperative cognitive dysfunction].

    Science.gov (United States)

    Miura, Rina; Hattori, Hideyuki

    2014-11-01

    The most important point for evaluation of the post-operative cognitive dysfunction is that we understand "cognitive function". First we described the definition of the "cognitive function" and second, outlined each function (dysfunction) and introduced the main assessment methods from the view point of neuropsychology. Cognitive function (dysfunction) described in this paper includes consciousness (confusional state, disturbance of consciousness), generalized attention (disorder of generalized attention), memory (amnesia), orientation (disorientation), executive function (dysexecutive syndrome), social cognition (social cognitive impairment), language (aphasia), cognition (agnosia), behavior (apraxia), directed attention (unilateral spatial neglect), and construction (constructional disorder).

  14. Heading in Soccer: Integral Skill or Grounds for Cognitive Dysfunction?

    Science.gov (United States)

    Kirkendall, Donald T.; Garrett, William E., Jr.

    2001-01-01

    Discusses how purposeful heading of soccer balls and head injuries affect soccer players' cognitive dysfunction. Cognitive deficits may occur for many reasons. Heading cannot be blamed when details of the actual event and impact are unknown. Concussions are the most common head injury in soccer and a factor in cognitive deficits and are probably…

  15. 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

    OBJECTIVES: To establish how long cognitive dysfunction lasts after concussion, and the extent to which it may be a predisposing risk factor for concussion, by examining the prevalence of cognitive dysfunction among young men who have sustained concussion. DESIGN: Observational study. SETTING......: 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...... screening test, dichotomised as dysfunctional or non-dysfunctional (20.4% of the general population of Danish men appearing before the draft board had a dysfunctional score). RESULTS: 700 of the 1220 men had been tested after sustaining concussion; 520 had been tested before concussion. Four (50...

  16. Cognitive dysfunction in depression - pathophysiology and novel targets

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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......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...

  17. Diagnostic Accuracy of a New Instrument for Detecting Cognitive Dysfunction in an Emergent Psychiatric Population: The Brief Cognitive Screen

    National Research Council Canada - National Science Library

    Cercy, Steven P; Simakhodskaya, Zoya; Elliott, Aaron

    2010-01-01

    .... The authors developed a new cognitive screening instrument, the Brief Cognitive Screen (BCS), with the aim of improving diagnostic accuracy for cognitive dysfunction in the psychiatric emergency department...

  18. 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

  19. 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

    2016-10-10

    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.

  20. Prior infection exacerbates postoperative cognitive dysfunction in aged rats

    NARCIS (Netherlands)

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

    2015-01-01

    Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro) inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed

  1. 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.

    2014-01-01

    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.

  2. Cognitive dysfunction in major depression and Alzheimer's disease is associated with hippocampus–prefrontal cortex dysconnectivity

    Directory of Open Access Journals (Sweden)

    Sampath D

    2017-06-01

    Full Text Available Dayalan Sampath,1 Monica Sathyanesan,1,2 Samuel S Newton1,2 1Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, 2Sioux Falls VA Healthcare System, Sioux Falls, SD, USA Abstract: Cognitive dysfunction is prevalent in psychiatric disorders. Deficits are observed in multiple domains, including working memory, executive function, attention, and information processing. Disability caused by cognitive dysfunction is frequently as debilitating as the prominent emotional disturbances. Interactions between the hippocampus and the prefrontal cortex are increasingly appreciated as an important link between cognition and emotion. Recent developments in optogenetics, imaging, and connectomics can enable the investigation of this circuit in a manner that is relevant to disease pathophysiology. The goal of this review is to shed light on the contributions of this circuit to cognitive dysfunction in neuropsychiatric disorders, focusing on Alzheimer’s disease and depression. Keywords: hippocampus, prefrontal cortex, cognition, depression, Alzheimer’s disease

  3. 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...

  4. 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...

  5. Cognitive dysfunction and its determinants in patients with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Vinod Varghese

    2016-01-01

    Full Text Available Introduction: Neurocysticercosis (NCC is the most common parasitic infection of man. In addition to a headache, seizures, and focal deficits, this is associated with significant cognitive dysfunction. Many studies revealed that the number and location of lesions are not always responsible for cognitive dysfunction. Cholinesterase and pseudocholinesterase are found in the walls of the cysticercus which could contribute to cholinergic depletion and thus cognitive dysfunction. Patients and Methods: A total of 43 patients who presented with NCC were evaluated for cognitive deficits, as well as cholinesterase levels in cerebrospinal fluid (CSF with control CSF from patients undergoing spinal anesthesia. Blood levels of interleukin-10 and tumor necrosis factor alpha were also estimated and correlated with cognitive deficits. Results: There is a mild increase in the acetylcholinesterase in CSF of patients compared to controls, but it did not correlate with cognitive deficits. There is an increase in interleukins to a significant level which correlates with vesicular stage of the organism and cognitive impairment. The number of lesions also correlated with cognitive impairment even though the location did not. The domains of cognitive deficits seen are sustained attention, category fluency, verbal working memory, planning, set shifting, verbal learning, visual memory, and construction. Discussion and Conclusion: NCC is associated with multi-domain cognitive impairment correlates with vescicular stage, proinflammatory cytokines and number of lesions but not location, vesicular stage, and proinflammatory cytokines.

  6. Cognitive Dysfunction and its Determinants in Patients with Neurocysticercosis

    Science.gov (United States)

    Varghese, Vinod; Chandra, Sadanandavalli Retnaswami; Christopher, Rita; Rajeswaran, Jamuna; Prasad, Chandrajit; Subasree, R.; Issac, Thomas Gregor

    2016-01-01

    Introduction: Neurocysticercosis (NCC) is the most common parasitic infection of man. In addition to a headache, seizures, and focal deficits, this is associated with significant cognitive dysfunction. Many studies revealed that the number and location of lesions are not always responsible for cognitive dysfunction. Cholinesterase and pseudocholinesterase are found in the walls of the cysticercus which could contribute to cholinergic depletion and thus cognitive dysfunction. Patients and Methods: A total of 43 patients who presented with NCC were evaluated for cognitive deficits, as well as cholinesterase levels in cerebrospinal fluid (CSF) with control CSF from patients undergoing spinal anesthesia. Blood levels of interleukin-10 and tumor necrosis factor alpha were also estimated and correlated with cognitive deficits. Results: There is a mild increase in the acetylcholinesterase in CSF of patients compared to controls, but it did not correlate with cognitive deficits. There is an increase in interleukins to a significant level which correlates with vesicular stage of the organism and cognitive impairment. The number of lesions also correlated with cognitive impairment even though the location did not. The domains of cognitive deficits seen are sustained attention, category fluency, verbal working memory, planning, set shifting, verbal learning, visual memory, and construction. Discussion and Conclusion: NCC is associated with multi-domain cognitive impairment correlates with vescicular stage, proinflammatory cytokines and number of lesions but not location, vesicular stage, and proinflammatory cytokines. PMID:27114627

  7. 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...

  8. ROLANDIC EPILEPSY OF CHILDHOOD: CORRECTION OF COGNITIVE DYSFUNCTIONS

    Directory of Open Access Journals (Sweden)

    S.V. Balkanskaya

    2008-01-01

    Full Text Available The paper is dedicated to the problem of cognitive dysfunctions in pediatric patients with rolandic epilepsy (benign partial epilepsy of childhood. Russian nootropic drug pantoham (hopantenic acid was used for correction of cognitive deficit. Quantitative data obtained via psihomat testing computer system were utilised for verification of principle cognitive functions before and after treatment with hopantenic acid in school age patients undergoing basic antiepileptic therapy. Positive effect of the drug on studied cognitive functions' indices was demonstrated.Key words: children, epilepsy, cognitive functions, hopantenic acid.

  9. Features of cognitive dysfunction in patients with depressive disorder and cerebrovascular pathology

    Directory of Open Access Journals (Sweden)

    Olga Prokhorova

    2017-09-01

    Full Text Available Background. In recent years, there has been an increase in the number of elderly people, and at the same time the accumulation of mental and somatic diseases inherent in these age categories. Depression, dementia and cardiovascular disease continue to occupy leading positions. Executive dysfunction syndrome in patients with organic depressive disorder with cerebrovascular pathology is one of the pathognomonic features of violation of higher brain functions in subcortical ischemic depression, which is important for the prognosis of the disease, provision of timely medical care, development of preventive measures and improvement of patients' quality of life. Materials and methods. Using TMT and Strup tests, 138 patients with depressive disorder were screened for the purpose of detecting cognitive dysfunction. Results. More pronounced cognitive dysfunction in the form of violation of the executive function, cognitive control, volume and distribution of attention was observed in patients with organic depressive disorder and signs of subcortical ischemia of the GM. Differences in the structure of violations of cognition are caused by zones of morphological defeat of the GM and the rupture of cortico-strial paths. Conclusions. Thus, in patients with subcortical ischemic depression, there is a syndrome of executive dysfunction, which is the leading cause of subcortical ischemic dementia. Ability to develop and implement a comprehensive program for the recovery of cognitive dysfunction will improve the quality of life of patients.

  10. Cognitive dysfunction in bipolar disorder and schizophrenia

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...... 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...

  11. Relationships among maladaptive cognitive content, dysfunctional cognitive processes, and borderline personality features.

    Science.gov (United States)

    Geiger, Paul J; Peters, Jessica R; Sauer-Zavala, Shannon E; Baer, Ruth A

    2013-08-01

    Previous research has demonstrated that maladaptive cognitive content, including dysfunctional attitudes and negative automatic thoughts, is associated with emotional distress. Similarly, dysfunctional cognitive processes, including thought suppression and rumination, have been shown to intensify psychological difficulties. Although maladaptive cognitive content and dysfunctional processes have been linked to borderline personality disorder (BPD), most research has been conducted with Axis I disorders. This study examined the incremental validity of dysfunctional cognitive content and processes in predicting BPD symptom severity, controlling for trait negative affect, in a sample of undergraduate students (N = 85), including many with high levels of BPD features. Although nearly all variables were significantly correlated with BPD features, final regression models suggest that rumination and thought suppression are stronger independent predictors of BPD features than automatic thoughts, dysfunctional attitudes, and trait negative affect. These results suggest the importance of targeting thought suppression and rumination in BPD.

  12. Does cognitive dysfunction conform to a distinctive pattern in obstructive sleep apnea syndrome?

    Science.gov (United States)

    Antonelli Incalzi, Raffaele; Marra, Camillo; Salvigni, Bruna Lorena; Petrone, Albino; Gemma, Antonella; Selvaggio, David; Mormile, Flaminio

    2004-03-01

    Obstructive sleep apnea (OSA) is a recognized cause of cognitive dysfunction. By using a cross-sectional comparative study, we aimed to verify whether neuropsychological performance of untreated OSA patients conforms to a distinctive pattern. Forty-nine newly diagnosed, untreated OSA patients, 27 with multi-infarctual dementia (MID), 31 with mild to moderate dementia of Alzheimer type (DAT) and 63 with severe chronic obstructive pulmonary disease (COPD), all free from major comorbid dementing conditions were chosen for the study. The groups were matched for age and education. We found a bimodal distribution of cognitive performance in OSA group, which was therefore divided into two clusters having better (OSAb, n = 35) and worse (OSAw, n = 14) performance on a battery of 10 cognitive indexes. Cognitive performances of OSAb, OSAw, MID, DAT and COPD were compared by discriminant analysis. OSAb performed better than OSAw in all but one test. Deductive thinking and verbal attainment were more severely impaired in OSAw than in COPD patients. Constructive ability, deductive thinking and both verbal attainment and immediate memory were comparably impaired in OSAw and DAT. The mean neuropsychological scores of OSAw and MID were comparable, but 71% of OSAw patients had a distinctive cognitive profile, i.e. a group specific pattern of cognitive dysfunction, according to discriminant analysis. One of four newly diagnosed OSA patients had a severe and distinctive neuropsychological dysfunction mainly involving inductive and deductive thinking, and constructive ability. Some analogy with cognitive pattern of MID suggests that a mainly subcortical damage underlies this dysfunction.

  13. 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....

  14. Association among depression, cognitive impairment and executive dysfunction after stroke

    Directory of Open Access Journals (Sweden)

    Luisa Terroni

    Full Text Available ABSTRACT The relationship between depression and cognitive impairment, frequent after stroke, is complex and has not been sufficiently elucidated. Objective: To review the relationship between post-stroke depression and cognitive impairment. Methods: We performed a PubMed database search spanning the last ten years, using the terms post-stroke depression, cognitive dysfunction, cognitive impairment and neuropsychological tests. Our target studies were original quantitative studies that investigated the relationship between post-stroke depression (PSD and cognitive impairment in stroke patients. Articles published in English, Spanish, Italian and Portuguese were considered. Selection criteria were the use of neuropsychological tests to assess cognitive function, and of either instruments to diagnose major depression, or scales to assess depressive symptoms, within the first three months after stroke. Results: Six original quantitative studies fulfilled the criteria. The prevalence of PSD within the first three months after stroke ranged from 22% to 31%. Incidence ranged from 25% to 27% and was evaluated in only two studies. PSD was associated with increased cognitive impairment. Cognitive impairment was reported in 35.2% to 87% of the patients. Post-stroke cognitive deficits were reported mostly in executive function, memory, language, and speed of processing. Conclusion: Executive dysfunction and depression occur in stroke survivors, are frequently coexistent, and also associated with worse stroke prognosis. Healthcare professionals need to address and provide adequate treatment for depression and executive dysfunctions in stroke patients early in the first three months after stroke. Future studies should evaluate the efficacy of programs evaluating the early detection and treatment of PSD and executive dysfunction in stroke survivors.

  15. Can music alleviate cognitive dysfunction in schizophrenia?

    Science.gov (United States)

    Glicksohn, J; Cohen, Y

    2000-01-01

    It has recently been reported that students performed relatively better on cognitive tasks after listening to music. Conceivably, music might reduce the level of arousal in subjects who are tense, thereby improving their performance. A test case would be schizophrenic subjects, noted for poor performance on tasks demanding attention, who have been characterized as suffering from hyperarousal, which mediates these attentional deficits. We investigated whether cognitive task performance could be facilitated by music in schizophrenics and report a beneficial effect. Copyright 2000 S. Karger AG, Basel

  16. Cognitive dysfunction in children with brain tumors at diagnosis

    Science.gov (United States)

    Studer, Martina; Ritter, Barbara Catherine; Steinlin, Maja; Leibundgut, Kurt; Heinks, Theda

    2015-01-01

    Background Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo‐ and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS). Methods Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1–16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and his/her parent(s) completed self‐report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy, or irradiation. Groups were comparable with regard to age, gender, and socioeconomic status. Results Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory, and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed, and verbal comprehension were preserved at the time of measurement. Conclusion Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school. Pediatr Blood Cancer 2015;62:1805–1812. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc. PMID:26053691

  17. Screening for cognitive dysfunction in unipolar depression

    DEFF Research Database (Denmark)

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

    2016-01-01

    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. Cytochrome P450 polymorphism and postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

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

    2012-01-01

    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 cyto...

  19. Prior infection exacerbates postoperative cognitive dysfunction in aged rats

    NARCIS (Netherlands)

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

    2015-01-01

    Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro) inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasm

  20. 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 o...... minimal invasive surgery, multi-modal non-opioid pain management and pharmacological manipulation of the inflammatory response and sleep architecture....

  1. 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

  2. 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......: /st>Danish patients enrolled between November 1994 and October 2000 in the two International Studies of Postoperative Cognitive Dysfunction (ISPOCD 1 and 2) were followed until July 1, 2011. Cognitive performance was assessed at three time points: before operation, at 1 week, and 3 months after...... developed dementia during follow-up. The hazard ratio (95% CI) for any dementia diagnoses in patients with POCD at 1 week (n=118) and POCD at 3 months (n=57) after surgery compared with those without POCD was 1.16 (0.48-2.78), P=0.74, and 1.50 (0.51-4.44); P=0.47, respectively. CONCLUSIONS: /st...

  3. Cortical network dysfunction caused by a subtle defect of myelination

    Science.gov (United States)

    Poggi, Giulia; Boretius, Susann; Möbius, Wiebke; Moschny, Nicole; Baudewig, Jürgen; Ruhwedel, Torben; Hassouna, Imam; Wieser, Georg L.; Werner, Hauke B.; Goebbels, Sandra

    2016-01-01

    Subtle white matter abnormalities have emerged as a hallmark of brain alterations in magnetic resonance imaging or upon autopsy of mentally ill subjects. However, it is unknown whether such reduction of white matter and myelin contributes to any disease‐relevant phenotype or simply constitutes an epiphenomenon, possibly even treatment‐related. Here, we have re‐analyzed Mbp heterozygous mice, the unaffected parental strain of shiverer, a classical neurological mutant. Between 2 and 20 months of age, Mbp+/‐ versus Mbp+/+ littermates were deeply phenotyped by combining extensive behavioral/cognitive testing with MRI, 1H‐MR spectroscopy, electron microscopy, and molecular techniques. Surprisingly, Mbp‐dependent myelination was significantly reduced in the prefrontal cortex. We also noticed a mild but progressive hypomyelination of the prefrontal corpus callosum and low‐grade inflammation. While most behavioral functions were preserved, Mbp+/‐ mice exhibited defects of sensorimotor gating, as evidenced by reduced prepulse‐inhibition, and a late‐onset catatonia phenotype. Thus, subtle but primary abnormalities of CNS myelin can be the cause of a persistent cortical network dysfunction including catatonia, features typical of neuropsychiatric conditions. GLIA 2016;64:2025–2040 PMID:27470661

  4. 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.

  5. 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. 

  6. 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...

  7. Cytochrome P450 polymorphism and postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... 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...

  8. The relationship between cognitive dysfunction and coping abilities in schizophrenia.

    Science.gov (United States)

    Wilder-Willis, Kelly E; Shear, Paula K; Steffen, John J; Borkin, Joyce

    2002-06-01

    Cognitive dysfunction is a core feature of schizophrenia [Psychiatr. Clin. North Am., 16 (1993) 295; Psychopharmacology: The fourth generation of progress, Raven Press, New York (1995) 1171; Clinical Neuropsychology, Oxford University Press, New York (1993) 449] and is related to psychosocial functioning in this population [Am. J. Psychiatry, 153 (1996) 321]. It is unclear whether cognitive dysfunction is related to specific areas of functioning in schizophrenia, such as coping abilities. Individuals with schizophrenia have deficient coping skills, which may contribute to their difficulties dealing with stressors [Am. J. Orthopsychiatry, 62 (1992) 117; J. Abnorm. Psychol., 82 (1986) 189]. The current study examined the relationship between coping abilities and cognitive dysfunction in a community sample of individuals with schizophrenia. It was hypothesized that executive dysfunction and mnemonic impairments would be positively related to deficiencies in active coping efforts involving problem solving and self-initiation (e.g. advocating for oneself and others with mental illness and becoming involved in meaningful activities, such as work), independent of the contributions of the general intellectual deficits associated with the disorder and psychiatric symptoms. The results indicated that both executive dysfunction and mnemonic impairments were related to decreased usage of active coping mechanisms after controlling for general intellectual deficits. Further, recognition memory made independent contributions to the prediction of coping involving action and help seeking after controlling for the effects of negative symptoms. These findings suggest that individuals with schizophrenia may be less flexible in their use of coping strategies, which may in turn contribute to their difficulties in coping with mental illness and its consequences.

  9. Cognitive dysfunction in patients with renal failure requiring hemodialysis

    Directory of Open Access Journals (Sweden)

    Rohini Thimmaiah

    2012-01-01

    Full Text Available Background and Objectives: Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. Materials and Methods: A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. Results: The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care, and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001. Conclusion: Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis.

  10. Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla Woznica; Ehrenreich, Hannelore; Christensen, Ellen M

    2014-01-01

    OBJECTIVE: Available drug treatments for bipolar disorder fail to reverse patients' cognitive deficits. Erythropoietin has neurotrophic actions and aids neurocognitive function. The aim of the study was to investigate the potential of erythropoietin to treat cognitive dysfunction in bipolar......; secondary outcomes were sustained attention and facial expression recognition; and tertiary outcomes were attention, executive function, subjective cognitive function, and mood. Analysis was by intention to treat, using repeated-measures analysis of covariance adjusted for stratification variables and mood...... in erythropoietin versus saline groups (P = .10). However, erythropoietin enhanced sustained attention (P = .001), recognition of happy faces (P = .03), and speed of complex information processing across learning, attention, and executive function (P = .01). These effects occurred in absence of changes in simple...

  11. 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

  12. Cognitive Reactivity, Dysfunctional Attitudes, and Depressive Relapse and Recurrence in Cognitive Therapy Responders

    Science.gov (United States)

    Jarrett, Robin B.; Minhajuddin, Abu; Borman, Patricia D.; Dunlap, Lauren; Segal, Zindel V.; Kidner, Cindy L.; Friedman, Edward S.; Thase, Michael E.

    2012-01-01

    Dysfunctional attitudes can foreshadow depressive relapse/recurrence. Priming mood, through induction paradigms, is hypothesized to activate dysfunctional attitudes. Cognitive reactivity (CR) refers to mood-linked increases in dysfunctional attitudes after priming. Here we explored the extent to which CR as well as residual, unprimed, dysfunctional attitudes predicted depressive relapse/recurrence among depressed patients who responded to acute phase cognitive therapy (CT). Consenting adults, aged 18–70, with recurrent major depressive disorder (n = 523) participated in a two-site randomized controlled trial examining the durability of continuation phase treatments. Patients received 16–20 sessions of CT. Among the 245 incompletely remitted responders, 213 agreed to undergo a mood induction paradigm. After 8 months of continuation phase treatments, participants were followed an additional 24 months. Although the mood induction significantly lowered mood in 80% of responders, the expected CR was not evident. By contrast, higher unprimed dysfunctional attitudes following CT did predict relapse/recurrence over 20 and 32 months post randomization. The findings of this large longitudinal study of incompletely remitted CT responders challenge the notion that it is necessary to prime mood in order to maximize dysfunctional attitudes’ prediction of relapse and/or recurrence. While findings cannot be generalized beyond CT responders, they emphasize the clinical importance of reducing dysfunctional attitudes in preventing depression. PMID:22445946

  13. 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

    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......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......, many aspects of cognitive impairment in patients with MS still need to be characterised. Standardised neuropsychological tests that are easy to administer and sensitive to disease-related abnormalities are needed to gain a better understanding of the factors affecting cognitive performance in patients...

  14. Chronic renal dysfunction and anaemia are associated with cognitive impairment in older patients with heart failure.

    Science.gov (United States)

    Pulignano, Giovanni; Del Sindaco, Donatella; Di Lenarda, Andrea; Tinti, Maria Denitza; Tarantini, Luigi; Cioffi, Giovanni; Tolone, Stefano; Pero, Gaetano; Minardi, Giovanni

    2014-06-01

    Cognitive impairment, anaemia and chronic kidney disease (CKD) are associated with mortality and disability in chronic heart failure patients. We hypothesized that anaemia and CKD are independent predictors of cognitive impairment in older patients with heart failure. One hundred and ninety community-living elderly patients aged at least 70 years, treated with optimized therapy for heart failure in stable clinical conditions, were prospectively studied. They underwent clinical and multidimensional assessment. Cognitive status was assessed by the Mini Mental State Examination. Cognitive impairment was defined as the Mini Mental State Examination score adjusted by age and educational level below 24. CKD was defined as the Cockcroft-Gault glomerular filtration rate below 60  ml/min and anaemia as haemoglobin below 12  g/dl. Cognitive impairment was diagnosed in 38.9% of patients, CKD in 85.7% and anaemia in 42.6%. Age, female sex, BMI, education less than 5 years, depressive symptoms, anaemia, CKD, disability and worse quality of life were significantly associated with cognitive impairment. Cognitive impairment involved primarily global cognitive deficit, memory, mental speed, attention, calculation and language. A significant relationship between haemoglobin levels and cognitive impairment was found, with the range of 15-16.5  g/dl having the lower prevalence of cognitive impairment (19.4%). At multivariate analysis, advanced age, low education level, anaemia and CKD were independently associated with cognitive impairment. Cox analysis showed that cognitive impairment was an independent predictor of hospitalization for worsening heart failure alone and combined with all-cause death. Cognitive impairment is common in elderly heart failure patients and is independently associated with anaemia and renal dysfunction. Further studies are needed to assess whether optimal treatment of anaemia and CKD may prevent the development of cognitive impairment in heart failure

  15. 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

  16. [Music therapy for dementia and higher cognitive dysfunction: a review].

    Science.gov (United States)

    Satoh, Masayuki

    2011-12-01

    Music is known to affect the human mind and body. Music therapy utilizes the effects of music for medical purposes. The history of music therapy is quite long, but only limited evidence supports its usefulness in the treatment of higher cognitive dysfunction. As for dementia, some studies conclude that music therapy is effective for preventing cognitive deterioration and the occurrence of behavioral and psychological symptoms of dementia (BPSD). In patients receiving music therapy for the treatment of higher cognitive dysfunction, aphasia was reported as the most common symptom. Many studies have been conducted to determine whether singing can improve aphasic symptoms: singing familiar and/or unfamiliar songs did not show any positive effect on aphasia. Melodic intonation therapy (MIT) is a method that utilizes melody and rhythm to improve speech output. MIT is a method that is known to have positive effects on aphasic patients. Some studies of music therapy for patients with unilateral spatial neglect; apraxia; hemiparesis; and walking disturbances, including parkinsonian gait, are available in the literature. Studies showed that the symptoms of unilateral spatial neglect and hemiparesis significantly improved when musical instruments were played for several months as a part of the music therapy. Here, I describe my study in which mental singing showed a positive effect on parkinsonian gait. Music is interesting, and every patient can go through training without any pain. Future studies need to be conducted to establish evidence of the positive effects of music therapy on neurological and neuropsychological symptoms.

  17. Post-stroke cognitive dysfunctions: A clinical and neuroimaging study

    Directory of Open Access Journals (Sweden)

    Andrei Yuryevich Emelin

    2013-01-01

    Full Text Available Clinical, neuropsychological, and neuroimaging examinations were made in 65 patients (52 men and 13 women aged 65.6±10.1 years who had experienced ischemic stroke. Cognitive impairments (CI were heterogeneous; regulatory functions, attention, and counting were most significantly affected in moderate CI. In mild dementia, mainly poor attention and regulatory dysfunctions were added by clearly-cut impairments of memory, orientation, and visual-spatial function. Brain atrophy, white matter changes, and small focal gray matter damages along with focal post-stroke changes were revealed by neuroimaging in most patients. It was found that besides the volume and location of a damage focus, the signs of impaired integrated mental activity of the brain, regulatory dysfunctions in particular, should be a necessary condition for the verification of post-stroke CI.

  18. Cognitive dysfunction in type 2 diabetes : detection and treatment in primary care

    NARCIS (Netherlands)

    Koekkoek, P.S.

    2015-01-01

    A less known complication of type 2 diabetes (T2DM) is cognitive dysfunction. Patients with T2DM already have cognitive decrements in an early stage of their disease. Cognitive dysfunction can lead to problems in diabetes treatment. Diabetes guidelines advise physicians to address patient’s

  19. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models.

    Science.gov (United States)

    Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

    2014-05-01

    Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

  20. Early cognitive dysfunction in the HD 51 CAG transgenic rat model of Huntington's disease.

    Science.gov (United States)

    Fink, Kyle D; Rossignol, Julien; Crane, Andrew T; Davis, Kendra K; Bavar, Angela M; Dekorver, Nicholas W; Lowrance, Steven A; Reilly, Mark P; Sandstrom, Michael I; von Hörsten, Stephan; Lescaudron, Laurent; Dunbar, Gary L

    2012-06-01

    Huntington's disease (HD) is a neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat that produces choreic movements, which are preceded by cognitive deficits. The HD transgenic rat (tgHD), which contains the human HD mutation with a 51 CAG repeat allele, exhibits motor deficits that begin when these rats are 12 months of age. However, there are no reports of cognitive dysfunction occurring prior to this. To assess whether cognitive dysfunction might precede motor deficits in tgHD rats, one group of 9-month-old male rats with homozygotic mutated genes and one group of wild-type (WT) rats underwent three testing phases in a unique Spatial Operant Reversal Test (SORT) paradigm, as well as assessment of spontaneous motor activity. After testing, morphological and histological examination of the brains were made. Results indicated that tgHD rats acquired the cued-response (Phase 1) portion of the SORT, but made significantly more errors during the reversal (Phase 2) and during the pseudorandomized reversals (Phase 3) portion of the study, when compared to WT rats. Analysis of the data using mathematical principles of reinforcement revealed no memory, motor, or motivational deficits. These results indicate that early cognitive dysfunction, as measured by the SORT, occur prior to motor deficits, gross anatomical changes, or cell loss in the tgHD rat with 51 CAG repeats, and suggest that this protocol could provide a useful screen for therapeutic studies.

  1. 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...... of appropriate controls. Furthermore, there are no internationally accepted criteria for defining POCD. This article aims to provide an update of current knowledge of the pathogenesis of POCD with a focus on perioperative pathophysiology and possible benefits achieved from an enhanced postoperative recovery...

  2. Posterior Tibial Tendon Dysfunction: An Overlooked Cause of Foot Deformity

    Science.gov (United States)

    Bubra, Preet Singh; Keighley, Geffrey; Rateesh, Shruti; Carmody, David

    2015-01-01

    Posterior tibial tendon dysfunction is the most common cause of adult acquired flatfoot. Degenerative changes in this tendon, lead to pain and weakness and if not identified and treated will progress to deformity of the foot and degenerative changes in the surrounding joints. Patients will complain of medial foot pain, weakness, and a slowly progressive foot deformity. A “too many toes” sign may be present and patients will be unable to perform a single heal raise test. Investigations such X-ray, ultrasound and magnetic resonance imaging will help stage the disease and decide on management. The optimal manage may change based on the progression of deformity and stage of disease. Early identification and prompt initiation of treatment can halt progression of the disease. The purpose of this article is to examine the causes, signs, symptoms, examinations, investigations and treatment options for posterior tibial tendon dysfunction. PMID:25810985

  3. Correlative study on the cognitive dysfunction of patients with myasthenia gravis

    Institute of Scientific and Technical Information of China (English)

    Wenli Chen; Wenmin Wang; Yi Wang

    2006-01-01

    blockage of acetylcholine at the peripheral neuromuscular junction. The mini-mental state examination,Wechsler memory scale, Wechsler adult intelligence scale, Boston naming test and Rey auditory verb and learning test, etc. Were used in the domestic and foreign studies of cognitive function of patients with MG for detecting memory, attention, fluency of reaction as well as information-processing velocity, etc.CONCLUSrON: It is thought in some investigations that disorders of memory, mental status, attention, fluency of reaction, information-processing velocity and other cognitive dysfunctions exist in patients with MG.However, there are some anti-standpoints on cognitive dysfunction caused by MG, and more work must be done for further exploration.

  4. Definition and application of neuropsychological test battery to evaluate postoperative cognitive dysfunction

    National Research Council Canada - National Science Library

    Valentin, Lívia Stocco Sanches; Pietrobon, Ricardo; Aguiar Junior, Wagner de; Rios, Ruth Pinto Camarão; Stahlberg, Mariane Galzerano; Menezes, Iolanda Valois Galvão de; Osternack-Pinto, Kátia; Carmona, Maria José Carvalho

    2015-01-01

    Objective To investigate the adequacy of the neuropsychological test battery proposed by the International Study of Postoperative Cognitive Dysfunction to evaluate this disorder in Brazilian elderly...

  5. The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease.

    Science.gov (United States)

    Phillips, Cristy; Baktir, Mehmet Akif; Das, Devsmita; Lin, Bill; Salehi, Ahmad

    2015-07-01

    Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly population worldwide. Despite the allocation of enormous amounts of funding and resources to studying this brain disorder, there are no effective pharmacological treatments for reducing the severity of pathology and restoring cognitive function in affected people. Recent reports on the failure of multiple clinical trials for AD have highlighted the need to diversify further the search for new therapeutic strategies for cognitive dysfunction. Thus, studies detailing the neuroprotective effects of physical activity (PA) on the brain in AD were reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline were explored. A MEDLINE database search was used to generate a list of studies conducted between January 2007 and September 2014 (n=394). These studies, along with key references, were screened to identify those that assessed the effects of PA on AD-related biomarkers and cognitive function. The search was not limited on the basis of intensity, frequency, duration, or mode of activity. However, studies in which PA was combined with another intervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and studies not written in English were excluded. Thirty-eight animal and human studies met entry criteria. Most of the studies suggested that PA attenuates neuropathology and positively affects cognitive function in AD. Although the literature lacked sufficient evidence to support precise PA guidelines, convergent evidence does suggest that the incorporation of regular PA into daily routines mitigates AD-related symptoms, especially when deployed earlier in the disease process. Here the protocols used to alter the progression of AD-related neuropathology and cognitive decline are highlighted, and the implications for physical therapist practice are discussed.

  6. 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

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 typ

  8. The effect of beta blockade on stress-induced cognitive dysfunction in adolescents.

    Science.gov (United States)

    Faigel, H C

    1991-07-01

    Test anxiety is severely disabling to students whose fear of examinations causes cognitive dysfunction that paralyzes their thinking the way stage fright impairs actors ability to act. In studies using subjective evaluations among actors and musicians, beta-blockade relieved stage fright and has been used informally to treat test anxiety in students without objective measures of effectiveness. The Scholastic Aptitude Test (SAT) was chosen as an objective test instrument to confirm the effect of beta-blockade on test anxiety and performance. Thirty-two high school students who had already taken the SAT before enrolling in this study and who had stress-induced cognitive dysfunction on exams were given 40 mg of propranolol one hour before they retook those tests. Mean SAT scores with beta-blockade were 130 points higher than on the initial SAT done before entering the study without medication (p = less than .01). A single dose of propranolol immediately before the SAT permitted improved performance in students prone to cognitive dysfunction due to test anxiety.

  9. Molecular Mechanisms of Cognitive Dysfunction following Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kendall Rae Walker

    2013-07-01

    Full Text Available 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.

  10. Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    Chung-Hsi Hsing

    2015-01-01

    Full Text Available Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs modulate cytokine synthesis and release. Trichostatin A (TSA, an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS- induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p. injected with vehicle or TSA (0.3 mg/kg. One hour later, they were injected (i.p. with saline or Escherichia coli LPS (1 mg/kg. We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO, TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression.

  11. Adenosine kinase inhibition protects against cranial radiation-induced cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Munjal M Acharya

    2016-06-01

    Full Text Available Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting, however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK. Adult rats exposed to cranial irradiation (10 Gy showed significant declines in performance of hippocampal-dependent cognitive function tasks (novel place recognition, novel object recognition, and contextual fear conditioning 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the fear conditioning task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP. Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection also against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS

  12. Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction.

    Science.gov (United States)

    Acharya, Munjal M; Baulch, Janet E; Lusardi, Theresa A; Allen, Barrett D; Chmielewski, Nicole N; Baddour, Al Anoud D; Limoli, Charles L; Boison, Detlev

    2016-01-01

    Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered

  13. Hypertension and cognitive dysfunction%高血压与认知功能障碍

    Institute of Scientific and Technical Information of China (English)

    董智瑀; 李云霞

    2016-01-01

    Constant hypertension at midlife is one of the important risk factors of cognitive dysfunction . The relationship between antihypertensive therapy and cognitive dysfunction is uncertain and needs further research. And other abnormal blood press such as increased pulse pressure, high nocturnal blood press level, nondipper status and exaggerated blood press variability is relative to cognitive dysfunction. From pathological point, hypertension can stimulate the growth of vascular smooth muscle cells and cause vascular remodeling. Then the reduced vascular regulatory capacity results in brain hypoperfusion and cognitive dysfunction. From imaging point, hypertension can not only faciliate the age factors on the structure of the brain, but also change the cerebral structures without the influence of the age factors. Many cross-sectional studies of the relationship between anti-hypertension and cognition found conflicting relationships with positive, negative and U-shaped asso-ciations. But the majority of longitudinal studies have found elevated blood pressure to be associated with cognitive decline. We search the word hypertension, cognitive dysfunction, antihypertensive agents as keywords in Pubmed and make a review about the connection among hypertension, antihy-pertension, structural change in the brain, functional change in vascular and cognitive dysfunction.%持续性高血压为认知功能障碍的重要危险因素。降压治疗与认知功能障碍间的关系还未明了,两者间的关系还有待进一步研究。其他异常血压形式,如脉压差增大、夜间收缩压偏高、非杓型高血压、血压变异率增加,都与认知功能障碍的发生有关。从病理角度,高血压会刺激血管平滑肌细胞生长,引起血管肥厚性重塑并降低血管自我调节能力,引起脑部灌注不足,产生认知功能障碍。从影像学角度,高血压能加重年龄因素对脑部结构的影响,还能使那些不易受到

  14. Long-term consequences of postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...... (prevalence ratio, 1.45 [1.03-2.04]; P = 0.03). CONCLUSIONS: Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor market prematurely, and dependency on social transfer payments....

  15. 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

    INTRODUCTION: 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. 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...

  16. Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation.

    Science.gov (United States)

    Gao, Zhi-Xin; Rao, Jin; Li, Yuan-Hai

    2017-02-01

    Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

  17. [Cardiovascular manifestations of thyrotoxicosis and thyroid dysfunction caused by amiodarone].

    Science.gov (United States)

    Simkó, József; Barta, Kitti; Szabó, Zoltán; Varga, Emma; Nagy, Endre; Lorincz, István

    2004-11-28

    Cardiovascular manifestations of thyrotoxicosis and thyroid dysfunction caused by amiodarone. The cardiovascular symptoms of thyrotoxicosis were described more than two hundred years ago and remained the basis of diagnosis in modern medicine. Myocardium, peripheral circulation and sympathetic nerve system, all affecting cardiovascular hemodynamics, are influenced by thyroid hormones in many ways. Sub-clinical hyperthyroidism is characterized by suppressed thyroid stimulating hormone and normal free triiodothyronine and free thyroxine levels. Cardiovascular symptoms: elevation of heart rate, myocardial contractility, stroke volume, myocardial oxygen consumption, systolic blood pressure and reduction in systemic vascular resistance and diastolic blood pressure can be often seen even in case of subclinical hyperthyroidism. Thyrotoxicosis exacerbates the symptoms of a preexisting heart disease, but it can also cause complaints in case of a structurally normal heart. The most common cardiac complications are arrhythmias (mainly atrial fibrillation), heart failure and hypertension. Amiodarone is used for the treatment and prevention of several arrhythmias. It is safely applicable even in case of left ventricular dysfunction. The more common application is limited by its side effects that can develop even at low doses and may involve several organs (thyroid gland, lungs, liver, heart, nerve system among others). The complex effect of amiodarone on thyroid function ranges from mild abnormalities of thyroid function tests to overt thyrotoxicosis or hypothyroidism.

  18. Subjective cognitive dysfunction associated with drug-induced parkinsonism in schizophrenia.

    Science.gov (United States)

    Kim, Jong-Hoon; Kim, Seong-Youn; Byun, Hee-Jung

    2008-01-01

    The authors investigated the subjective cognitive dysfunction associated with drug-induced parkinsonism (DIP) among 58 stabilized schizophrenic outpatients. Subjective cognitive dysfunction was comprehensively assessed using the Frankfurt Complaint Questionnaire (FCQ). Multivariate analysis revealed that the DIP group scored significantly higher on the total FCQ score than the non-DIP group. In phenomenological subscale scores, the DIP group had significantly higher scores on "deterioration of discrimination", "psychomotor disorder", and "perceptual disorder" than the non-DIP group. These results suggest that DIP is significantly associated with subjective cognitive-perceptual dysfunction, reflecting the complex nature of DIP that includes motor and cognitive aspects.

  19. 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.

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

    Science.gov (United States)

    Zhang, Marsha R; Red, Stuart D; 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.

  1. Cognitive Dysfunction in Chronic Renal Disease: Impact of Dialysis Modality

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    Recep AK

    2015-12-01

    Full Text Available OBJECTIVE: Cognitive dysfunction (CD is common among patients with chronic kidney disease (CKD and contributes to morbidity and mortality. We aimed to explore the factors involved in the development of CD in patients with CKD and to compare cognitive function between hemodialysis (HD and peritoneal dialysis (PD patients. MATERIAL and METHODS: We studied 122 patients with different stages of CKD, and divided them into two groups: Predialysis Group: included 60 CKD patients, (28 stage III and 34 stage IV; Dialysis Group: included 60 patients on dialysis therapy, (30 on HD and 30 on PD. Psychometric tests were done all patients. The results were compared with 41 healthy subjects. RESULTS: We found that the CD rate was higher in patients with CKD (24.6% than controls (0%, p<0.001. The Mini Mental Test score was found to be correlated with age (r=-0.428, hemoglobin (r=0.336, CRP (r=-0.311, and albumin (r=0.336; the Calculation Test score was found to be correlated with LDL cholesterol (r=-0.336; the Praxis Test Score was found to be correlated with duration of CKD (r=-0.204, HDL (r=0.188; and the Visual Memory Test score was found to be correlated with parathormone levels (r=-0.270. We found the CD rate to be higher in patients on HD (50% than on PD (23.3%, p=0.032. CONCLUSION: Our findings suggest that anemia, malnutrition and inflammation play an important role in the development of CD in our patients, and cognitive functions are better preserved in the PD group than the HD group.

  2. 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.

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

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    Yuliya Gennad'evna Samoylova

    2014-04-01

    Full Text Available BackgroundImpairment 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.ObjectiveTo identify the role of neurospecific markers in the diagnosis of cognitive dysfunction in patients with T1DM.Materials and MethodsA 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.ResultsThe study revealed increased levels of all neurospecific proteins, which correlated with parameters of hyperglycaemia and cognitive deficit (MoCA scores of <26 points. MRI of the brain revealed signs of grey matter atrophy and involvement of white matter, which correlated with the presence of chronic hyperglycaemia, cognitive impairment and microvascular complications.ConclusionChronic hyperglycemia can be involved in the pathogenesis of cognitive dysfunction in T1DM patients. More studies (prospective controlled and observational trials are needed to clarify the relationship of diabetes and central nervous system impairment.

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

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-fan; LI Yun-feng; CHEN Xiao; SUN Qing-fang

    2013-01-01

    Objective 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 sources 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.Study selection 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.Results 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.Conclusions Brain atrophy and hippocampal changes caused by excess secretion of cortisol are

  5. Markers of cardiac dysfunction in cognitive impairment and dementia.

    Science.gov (United States)

    Hilal, Saima; Chai, Yuek Ling; Ikram, Mohammad Kamran; Elangovan, Sakktivel; Yeow, Tan Boon; Xin, Xu; Chong, Jun Yi; Venketasubramanian, Narayanaswamy; Richards, Arthur Mark; Chong, Jenny P C; Lai, Mitchell Kim Peng; Chen, Christopher

    2015-01-01

    Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD).We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia.A case-control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale.We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64-49.79) and dementia (OR: 16.89; 95%CI: 2.02-142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23-48.58). These associations were independent of other vascular risk factors.In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD.

  6. Causes of immune dysfunction in hyperbilirubinemia model rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Min Sun; Ping Kang; Ke Tao

    2015-01-01

    Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods: A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high-dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results: In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group, MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P<0.05). In high-dose group, inflammotory factors levels and CD8+ T cells percentage were all higher than LPS control and NS group (P<0.05), while CD4+ T cells percentage was lower than NS group (P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF-κB signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.

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

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    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.

  8. Green tea consumption affects cognitive dysfunction in the elderly: a pilot study.

    Science.gov (United States)

    Ide, Kazuki; Yamada, Hiroshi; Takuma, Norikata; Park, Mijong; Wakamiya, Noriko; Nakase, Junpei; Ukawa, Yuuichi; Sagesaka, Yuko M

    2014-09-29

    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: 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Evaluation of the effects of group psychotherapy on cognitive function in patients with multiple sclerosis with cognitive dysfunction and depression

    Directory of Open Access Journals (Sweden)

    Emine Bilgi

    2015-02-01

    Full Text Available Objective This study will evaluate how decreasing depression severity via group psychotherapy affects the cognitive function of patients with multiple sclerosis (MS who are also diagnosed with depression and cognitive dysfunction. Method MS patients completed the Brief Repeatable Battery of Neuropsychological Tests and Beck Depression Inventory (BDI. The group members diagnosed with depression and cognitive dysfunction underwent group psychotherapy for 3 months. Upon completion of psychotherapy, both tests were readministered. Results Depression and cognitive dysfunction were comorbid in 15 (13.9% of patients. Although improvement was detected at the end of the 3-month group psychotherapy intervention, it was limited to the BDI and the Paced Auditory Test. Conclusion Group psychotherapy might decrease cognitive impairment in MS patients.

  11. An epigenetic hypothesis of aging-related cognitive dysfunction

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    Marsha R Penner

    2010-03-01

    Full Text Available This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

  12. Hereditary vulnerabilities to post-operative cognitive dysfunction and dementia.

    Science.gov (United States)

    Hogan, Kirk J

    2013-12-01

    In view of multiple prospective investigations reporting an incidence of 10% or greater in elderly patients after cardiac and non-cardiac procedures, it is surprising that no families, twins or even individual cases have been reported with persistent post-operative cognitive dysfunction (POCD) or post-operative dementia (POD) that is otherwise unexplained. As POCD and POD research has shifted in recent years from surgical and anesthetic variables to predictors of intrinsic, patient-specific susceptibility, a number of markers based on DNA sequence variation have been investigated. Nevertheless, no heritable, genomic indices of persistent POCD or post-operative dementia lasting 3 months or longer after surgery have been identified to date. The present manuscript surveys challenges confronting the search for markers of heritable vulnerability to POCD and POD, and proposes steps forward to be taken now, including the addition of surgical and anesthetic descriptors to ongoing longitudinal dementia protocols and randomized clinical trials (RCTs) comprising serial psychometric testing, and a fresh focus on phenotypes and genotypes shared between outliers with "extreme" POCD and POD traits.

  13. Congenital prosopagnosia--a common hereditary cognitive dysfunction in humans.

    Science.gov (United States)

    Kennerknecht, Ingo; Pluempe, Nina; Welling, Brigitte

    2008-01-01

    The apparent selectivity of agnosia for faces is termed prosopagnosia or face blindness. This cognitive dysfunction can be seen after traumatic events--involving at least the right occipital temporal region--or very frequently congenital in the absence of any detectable lesions. The familiarity of congenital prosopagnosia was studied in two independently ascertained collections of subjects with prosopagnosia. One was an unselected group of pupils and students who underwent a questionnaire based screening. The others were self reported subjects after having heard for the first time about the phenomenon of prosopagnosia from mass media citing our studies and/or from our homepage (www.prosopagnosia.de). Those who agreed with consecutive studies of their family members had mostly one or more prosopagnosic first degree relatives. The segregation patterns derived from 39 families are compatible with autosomal dominant inheritance. Hence, mutation(s) in one gene are sufficient for manifestation of the phenotype. Still fitting the concept of autosomal dominant inheritance, we have evidence for a slightly reduced penetrance (4 normal transmitters from distinct families) and one or two de novo mutations.

  14. Cause and Consequence: Mitochondrial Dysfunction Initiates and Propagates Neuronal Dysfunction, Neuronal Death and Behavioral Abnormalities in Age Associated Neurodegenerative Diseases

    Science.gov (United States)

    Gibson, Gary E.; Starkov, Anatoly; Blass, John P.; Ratan, Rajiv R.; Beal, M. Flint

    2009-01-01

    SUMMARY Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sub lethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the α-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhance ROS production in Alzheimer’s Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington’s Disease (HD), a movement disorder with cognitive features distinct form AD, complex II + III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a cross linking enzymes that can modulate transcrption, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic

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

    Science.gov (United States)

    Xu, Jiajun; Yang, Ming; Kosterin, Paul; Salzberg, Brian M; Milovanova, Tatyana N; Bhopale, Veena M; Thom, Stephen R

    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 1h 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 1h 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.

  16. NRSF and BDNF polymorphisms as biomarkers of cognitive dysfunction in adults with newly diagnosed epilepsy.

    Science.gov (United States)

    Warburton, Alix; Miyajima, Fabio; Shazadi, Kanvel; Crossley, Joanne; Johnson, Michael R; Marson, Anthony G; Baker, Gus A; Quinn, John P; Sills, Graeme J

    2016-01-01

    Cognitive dysfunction is a common comorbidity in people with epilepsy, but its causes remain unclear. It may be related to the etiology of the disorder, the consequences of seizures, or the effects of antiepileptic drug treatment. Genetics may also play a contributory role. We investigated the influence of variants in the genes encoding neuron-restrictive silencer factor (NRSF) and brain-derived neurotrophic factor (BDNF), proteins previously associated with cognition and epilepsy, on cognitive function in people with newly diagnosed epilepsy. A total of 82 patients who had previously undergone detailed neuropsychological assessment were genotyped for single nucleotide polymorphisms (SNPs) across the NRSF and BDNF genes. Putatively functional SNPs were included in a genetic association analysis with specific cognitive domains, including memory, psychomotor speed, and information processing. Cross-sectional and longitudinal designs were used to explore genetic influences on baseline cognition at diagnosis and change from baseline over the first year since diagnosis, respectively. We found a statistically significant association between genotypic variation and memory function at both baseline (NRSF: rs1105434, rs2227902 and BDNF: rs1491850, rs2030324, rs11030094) and in our longitudinal analysis (NRSF: rs2227902 and BDNF: rs12273363). Psychomotor speed was also associated with genotype (NRSF rs3796529) in the longitudinal assessment. In line with our previous work on general cognitive function in the healthy aging population, we observed an additive interaction between risk alleles for the NRSF rs2227902 (G) and BDNF rs6265 (A) polymorphisms which was again consistent with a significantly greater decline in delayed recall over the first year since diagnosis. These findings support a role for the NRSF-BDNF pathway in the modulation of cognitive function in patients with newly diagnosed epilepsy.

  17. Ccdc66 null mutation causes retinal degeneration and dysfunction.

    Science.gov (United States)

    Gerding, Wanda M; Schreiber, Sabrina; Schulte-Middelmann, Tobias; de Castro Marques, Andreia; Atorf, Jenny; Akkad, Denis A; Dekomien, Gabriele; Kremers, Jan; Dermietzel, Rolf; Gal, Andreas; Rülicke, Thomas; Ibrahim, Saleh; Epplen, Jörg T; Petrasch-Parwez, Elisabeth

    2011-09-15

    Retinitis pigmentosa (RP) is a group of human retinal disorders, with more than 100 genes involved in retinal degeneration. Canine and murine models are useful for investigating human RP based on known, naturally occurring mutations. In Schapendoes dogs, for example, a mutation in the CCDC66 gene has been shown to cause autosomal recessively inherited, generalized progressive retinal atrophy (gPRA), the canine counterpart to RP. Here, a novel mouse model with a disrupted Ccdc66 gene was investigated to reveal the function of protein CCDC66 and the pathogenesis of this form of gPRA. Homozygous Ccdc66 mutant mice lack retinal Ccdc66 RNA and protein expression. Light and electron microscopy reveal an initial degeneration of photoreceptors already at 13 days of age, followed by a slow, progressive retinal degeneration over months. Retinal dysfunction causes reduced scotopic a-wave amplitudes, declining from 1 to 7 months of age as well as an early reduction of the photopic b-wave at 1 month, improving slightly at 7 months, as evidenced by electroretinography. In the retina of the wild-type (WT) mouse, protein CCDC66 is present at highest levels after birth, followed by a decline until adulthood, suggesting a crucial role in early development. Protein CCDC66 is expressed predominantly in the developing rod outer segments as confirmed by subcellular analyses. These findings illustrate that the lack of protein CCDC66 causes early, slow progressive rod-cone dysplasia in the novel Ccdc66 mutant mouse model, thus providing a sound foundation for the development of therapeutic strategies.

  18. 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,

  19. 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 t

  20. 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.

  1. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    Science.gov (United States)

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  2. Hashimoto’s Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion

    OpenAIRE

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-01-01

    Hashimoto’s encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto’s encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto’s encephalopathy is very rare. We report a 65-year-old man wh...

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

    OpenAIRE

    2013-01-01

    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 thi...

  4. X Irradiation Induces Acute Cognitive Decline via Transient Synaptic Dysfunction.

    Science.gov (United States)

    Puspitasari, Anggraeini; Koganezawa, Noriko; Ishizuka, Yuta; Kojima, Nobuhiko; Tanaka, Natsume; Nakano, Takashi; Shirao, Tomoaki

    2016-04-01

    Cranial X irradiation can severely impair higher brain function, resulting in neurocognitive deficits. Radiation-induced brain injury is characterized by acute, early and late delayed changes, and morbidity is evident more than 6 months after irradiation. While the acute effects of radiation exposure on the brain are known, the underlying mechanisms remain unclear. In this study, we examined the acute effect of X radiation on synaptic function using behavioral analysis and immunohistochemistry. We found that 10 Gy whole-brain irradiation immediately after conditioning (within 30 min) impaired the formation of fear memory, whereas irradiation 24 h prior to conditioning did not. To investigate the mechanisms underlying these behavioral changes, we irradiated one hemisphere of the brain and analyzed synaptic function and adult neurogenesis immunohistochemically. We focused on drebrin, whose loss from dendritic spines is a surrogate marker of synaptopathy. The intensity of drebrin immunoreactivity started to decrease in the irradiated hemisphere 2 h after exposure. The immunostaining intensity recovered to preirradiation levels by 24 h, indicating that X radiation induced transient synaptic dysfunction. Interestingly, the number of newly generated neurons was not changed at 2 h postirradiation, whereas it was significantly decreased at 8 and 24 h postirradiation. Because irradiation 24 h prior to conditioning had no effect on fear memory, our findings suggest that radiation-induced death of newly-generated neurons does not substantially impact fear memory formation. The radiation-induced synaptic dysfunction likely caused a transient memory deficit during the critical period for fear memory formation (approximately 1-3 h after conditioning), which coincides with a change in drebrin immunostaining in the hippocampus, a structure critical for fear memory formation.

  5. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction

    Directory of Open Access Journals (Sweden)

    Hong Yan

    2016-01-01

    Full Text Available This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group, or burn injury combined with seawater immersion (BI group, or only immersion in seawater (I group, or control animals with no injury or immersion (C group. The circulating endothelial cell (CEC count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P<0.05. The von Willebrand factor (vWF activity, plasminogen activator inhibitor (PAI-1, and the ratio of thromboxane B2 (TXB2 to 6-keto-prostaglandin F1α (6-K-PGF1α in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

  6. 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.

  7. Developing interventions for cancer-related cognitive dysfunction in childhood cancer survivors.

    Science.gov (United States)

    Castellino, Sharon M; Ullrich, Nicole J; Whelen, Megan J; Lange, Beverly J

    2014-08-01

    Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes.

  8. 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.

  9. Z-Score LORETA Neurofeedback as a Potential Therapy in Cognitive Dysfunction and Dementia

    Directory of Open Access Journals (Sweden)

    Lucas Koberda J

    2014-11-01

    Full Text Available Introduction of QEEG/LORETA electrical brain imaging has improved our diagnostic ability in neuropsychiatric practice by enhancing identification of dysregulated cortical areas implicated in patient symptoms. Additional use of LORETA Z-score neuro feedback (NFB enables us to directly target these areas of dysregulation in order to improve associated symptoms. Based on the review of 250 patients treated in our clinic suffering from neuropsychiatric illness and treated with Z-score LORETA NFB, analysis of cases of cognitive dysfunction and dementia are presented. Specific areas of dysregulation attributed to particular conditions identified by LORETA are discussed. Follow up findings of QEEG/LORETA electrical imaging after NFB therapy (including computerized cognitive testing results are shown. This paper summarizes my experience with LORETA Z-score NFB as a tool for therapy of cognitive dysfunction. In addition, this form of NFB is able to improve cognitive functions of individuals suffering from memory, information processing and other cognitive dysfunctions. Extensive presentations of selected cases are used for demonstration of results from my practice. Twenty five out of 35 patients (71% who suffered from static cognitive dysfunction were identified as having an objective improvement (on average 10 points through cognitive testing with NFB therapy. In addition, the subjective cognitive improvement and an objective reduction of QEEG abnormalities with NFB were also achieved in most of the patients. These results are very promising and indicate good effectiveness of LORETA Z-score NFB as cognitive enhancement tool.

  10. 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.

  11. The relationship between Impulse Control Disorders and cognitive dysfunctions in Parkinson's Disease: a meta-analysis.

    Science.gov (United States)

    Santangelo, Gabriella; Raimo, Simona; Barone, Paolo

    2017-02-24

    Impulse Control Disorders (ICD) are associated with impairment in cognitive flexibility and cortical inhibition. In Parkinson's Disease (PD) the relationship between ICD and cognitive dysfunctions is still unclear: some studies found different cognitive profiles between Parkinsonians with and without ICD, whereas others did not. Moreover, findings from studies on ICD in PD are conflicting on which cognitive function is altered. A meta-analysis of 34 studies was performed to shed light on relationship between ICD and cognitive dysfunctions and to reveal the cognitive function compromised in Parkinsonians with ICD. Data were analyzed in global cognitive functioning, memory, executive functions, attention/working memory, language, and visuospatial functions. Significant relationship between ICD and dysfunction of abstraction ability/concept formation, set-shifting, visuospatial/constructional abilities and decision-making was found. These findings suggested that people affected by PD with specific frontal dysfunctions are more vulnerable to develop ICD when they take antiparkinsonian drug. Evaluation of specific cognitive functions in routine clinical practice might help to detect those people with PD susceptible to ICD before treating them with antiparkinsonian drugs.

  12. 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 candidate genes, high opioid dose, and cognitive dysfunction. METHODS: Cross-sectional multicenter study (European Pharmacogenetic Opioid Study, 2005-2008); 1586 patients; 113 SNPs from 41 genes. Inclusion criteria: cancer, age ≥18 year, opioid treatment, and available genetic data. Cognitive assessment...

  13. Dysfunctional cognitions and their emotional, behavioral, and functional correlates in adults with attention deficit hyperactivity disorder (ADHD): is the cognitive-behavioral model valid?

    Science.gov (United States)

    Torrente, Fernando; López, Pablo; Alvarez Prado, Dolores; Kichic, Rafael; Cetkovich-Bakmas, Marcelo; Lischinsky, Alicia; Manes, Facundo

    2014-07-01

    To investigate the presence of dysfunctional cognitions in adults with ADHD and to determine whether these cognitions are associated with emotional symptoms, maladaptive coping, and functional impairment, as predicted by the cognitive-behavioral model. A total of 35 adult participants with ADHD, 20 nonclinical controls, and 20 non-ADHD clinical controls were assessed with measures of ADHD symptoms, dysfunctional cognitions, depression and anxiety symptoms, coping strategies, and quality of life. ADHD group showed elevated scores of dysfunctional cognitions relative to nonclinical control group and comparable with clinical control group. Dysfunctional cognitions were strongly associated with emotional symptoms. ADHD group also showed elevated scores in maladaptive coping strategies of the escape-avoidance type. Life impairment was satisfactorily predicted in data analysis when ADHD symptoms, dysfunctional cognitions, and emotional symptoms were fitted into a regression model. Cognitive-behavioral therapy model appears to be a valid complementary model for understanding emotional and life impairment in adults with ADHD. © 2012 SAGE Publications.

  14. Music intervention on cognitive dysfunction in healthy older adults: a systematic review and meta-analysis.

    Science.gov (United States)

    Xu, Bing; Sui, Yi; Zhu, Chunyan; Yang, Xiaomei; Zhou, Jin; Li, Li; Ren, Li; Wang, Xu

    2017-03-08

    The background of this study is to determine whether there is an association between music intervention and cognitive dysfunction therapy in healthy older adults, and if so, whether music intervention can be used as first-line non-pharmacological treatment. The method used in this study is to conduct a systematic review and meta-analysis of clinical trials that examined the effects of music intervention on patient-relevant and disease-specific outcomes. A comprehensive literature was performed on PubMed, EMbase and the Cochrane Library from inception to September 2016. A total of 10 studies (14 analyses, 966 subjects) were included; all of them had an acceptable quality based on the PEDro scale score and CASP scale score. Compared with control group, the standardized mean difference was 0.03 (-0.18 to 0.24) for cognitive function as primary outcome by random effect model; secondary outcomes were included disruptive behavior, depressive score, anxiety and quality of life. No evidence of publication bias could be found in funnel plots, Begg's test and Egger's test. Subgroup analyses showed that intervention method, comparator, trial design, trial period and outcome measure instruments made little difference in outcomes. Meta-regression might not identify cause of heterogeneity. This study is registered with PROSPERO, number CRD442016036264. There was positive evidence to support the use of music intervention on treatment of cognitive function.

  15. 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

    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....

  16. 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...

  17. HDL dysfunction in diabetes: causes and possible treatments

    Science.gov (United States)

    Farbstein, Dan; Levy, Andrew P

    2012-01-01

    HDL is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. These functions include cholesterol efflux and reverse cholesterol transport, antioxidative and anti-inflammatory activities. However, HDL has been shown to undergo a loss of function in several pathophysiological states, as in the acute phase response, obesity and chronic inflammatory diseases. Some of these diseases were also shown to be associated with increased risk for cardiovascular disease. One such disease that is associated with HDL dysfunction and accelerated atherosclerosis is diabetes mellitus, a disease in which the HDL particle undergoes diverse structural modifications that result in significant changes in its function. This review will summarize the changes that occur in HDL in diabetes mellitus and how these changes lead to HDL dysfunction. Possible treatments for HDL dysfunction are also briefly described. PMID:22390807

  18. Multiorgan Dysfunction Caused by Travel-associated African Trypanosomiasis

    Science.gov (United States)

    Peters, Joanna R.; Hall, Alison; Bailey, J. Wendi; Noyes, Harry A.; Rimington, Jane E.; Beeching, Nicholas J.; Squire, S. Bertel; Beadsworth, Mike B.J.

    2012-01-01

    We describe a case of multiorgan dysfunction secondary to Trypanosoma brucei rhodesiense infection acquired on safari in Zambia. This case was one of several recently reported to ProMED-mail in persons who had traveled to this region. Trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of Africa. PMID:22305185

  19. Multiorgan dysfunction caused by travel-associated African trypanosomiasis.

    Science.gov (United States)

    Cottle, Lucy E; Peters, Joanna R; Hall, Alison; Bailey, J Wendi; Noyes, Harry A; Rimington, Jane E; Beeching, Nicholas J; Squire, S Bertel; Beadsworth, Mike B J

    2012-02-01

    We describe a case of multiorgan dysfunction secondary to Trypanosoma brucei rhodesiense infection acquired on safari in Zambia. This case was one of several recently reported to ProMED-mail in persons who had traveled to this region. Trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of Africa.

  20. Predicting Behavior from Cognitive Cause Maps of a Work Setting.

    Science.gov (United States)

    Komocar, John

    Cognitive cause maps permit a topological investigation of the complexity of organizational events and behaviors. Because cognitive cause maps are believed to be ordered according to a givens-means-ends schema, they contain information about an individual's motivation structure. In a work setting an individual engages in several different acts.…

  1. Beyond Emotional and Spatial Processes: Cognitive Dysfunction in a Depressive Phenotype Produced by Long Photoperiod Exposure.

    Science.gov (United States)

    Barnes, Abigail K; Smith, Summer B; Datta, Subimal

    2017-01-01

    Cognitive dysfunction in depression has recently been given more attention and legitimacy as a core symptom of the disorder. However, animal investigations of depression-related cognitive deficits have generally focused on emotional or spatial memory processing. Additionally, the relationship between the cognitive and affective disturbances that are present in depression remains obscure. Interestingly, sleep disruption is one aspect of depression that can be related both to cognition and affect, and may serve as a link between the two. Previous studies have correlated sleep disruption with negative mood and impaired cognition. The present study investigated whether a long photoperiod-induced depressive phenotype showed cognitive deficits, as measured by novel object recognition, and displayed a cognitive vulnerability to an acute period of total sleep deprivation. Adult male Wistar rats were subjected to a long photoperiod (21L:3D) or a normal photoperiod (12L:12D) condition. Our results indicate that our long photoperiod exposed animals showed behaviors in the forced swim test consistent with a depressive phenotype, and showed significant deficits in novel object recognition. Three hours of total sleep deprivation, however, did not significantly change novel object recognition in either group, but the trends suggest that the long photoperiod and normal photoperiod groups had different cognitive responses to total sleep deprivation. Collectively, these results underline the extent of cognitive dysfunction present in depression, and suggest that altered sleep plays a role in generating both the affective and cognitive symptoms of depression.

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

    DEFF Research Database (Denmark)

    Steinmetz, J.; Rasmussen, L.S.

    2008-01-01

    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......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...... 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...

  3. Effects of early adolescent environmental enrichment on cognitive dysfunction, prefrontal cortex development, and inflammatory cytokines after early life stress.

    Science.gov (United States)

    do Prado, Carine H; Narahari, Tanya; Holland, Freedom H; Lee, Ha-Neul; Murthy, Shashi K; Brenhouse, Heather C

    2016-05-01

    Early postnatal stress such as maternal separation causes cognitive dysfunction later in life, including working memory deficits that are largely mediated by the prefrontal cortex. Maternal separation in male rats also yields a loss of parvalbumin-containing prefrontal cortex interneurons in adolescence, which may occur via inflammatory or oxidative stress mechanisms. Environmental enrichment can prevent several effects of maternal separation; however, effects of enrichment on prefrontal cortex development are not well understood. Here, we report that enrichment prevented cognitive dysfunction in maternally separated males and females, and prevented elevated circulating pro-inflammatory cytokines that was evident in maternally separated males, but not females. However, enrichment did not prevent parvalbumin loss or adolescent measures of oxidative stress. Significant correlations indicated that adolescents with higher oxidative damage and less prefrontal cortex parvalbumin in adolescence committed more errors on the win-shift task; therefore, maternal separation may affect cognitive dysfunction via aberrant interneuron development. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 482-491, 2016. © 2015 Wiley Periodicals, Inc.

  4. 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 charact......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...... support the senescent dog with spontaneous cognitive dysfunction as a valuable non-transgenic model for further investigations of the molecular events involved in the neurodegenerative processes associated with aging and early stage AD, especially the Aβ-related pathology....

  5. 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

  6. 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 eleva

  7. Omega 3 Fatty Acids: Novel Neurotherapeutic Targets for Cognitive Dysfunction in Mood Disorders and Schizophrenia?

    Science.gov (United States)

    Knöchel, Christian; Voss, Martin; Grüter, Florian; Alves, Gilberto S; Matura, Silke; Sepanski, Beate; Stäblein, Michael; Wenzler, Sofia; Prvulovic, David; Carvalho, André F; Oertel-Knöchel, Viola

    2015-01-01

    An increasing body of evidences from preclinical as well as epidemiological and clinical studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning. In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and affective disorders is warranted.

  8. 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

    2016-02-17

    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.

  9. Special Supplement Introduction: The Fourth Kraepelin Symposium-Cognitive Dysfunction in Schizophrenia: Origins and Innovative Treatment.

    Science.gov (United States)

    Schaub, Annette; Falkai, Peter

    2016-07-01

    This Special Supplement presents reports from working groups meeting at the Fourth Kraepelin Symposium in Munich, Germany, in September 2014. It covers the origins and therapy of cognitive dysfunction in schizophrenia. Cognitive deficits are core symptoms of schizophrenia being decisive for the long-term prognosis only improved moderately by antipsychotic treatment, however, showing more evidence for cognitive remediation. The authors refer to neurobiological and psychological underpinnings of cognitive deficits and to innovative treatment interventions aimed at improving cognitive dysfunction in order to improve outcome and to support coping with the illness. Therapeutic approaches include aerobic exercise, cognitive training, psychoeducation, cognitive therapy, noninvasive brain stimulation and pharmacotherapy in acute to post-acute patients. The supplement also presents novel diagnostic tools for early recognition, such as biomarkers, as well as cognitive training to prevent worsening of symptoms in individuals at clinical high risk for psychosis. In recent years there has been progress in basic science and outcomes research as well as psychopharmacological and psychological treatment options. Despite of this, treatment of cognitive deficits needs significant improvement and further research is needed. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. 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

    2014-01-01

    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. PMID:25206795

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    This study established an aged rat model of cognitive dysfunction using anesthesia with 2%iso-lfurane 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 isolfurane also signiifcantly increased the levels of N,N-diethy-lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isolfurane-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 isolfurane-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.

  12. 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.

  13. PBA regulates neurogenesis and cognition dysfunction after repeated electroconvulsive shock in a rat model.

    Science.gov (United States)

    Yao, Zhao-Hui; Kang, Xiang; Yang, Liu; Niu, Yi; Lu, Ye; Nie, Li

    2015-12-15

    Electroconvulsive therapy (ECT) was widely used to treat the refractory depression. But ECT led to the cognitive deficits plaguing the depression patients. The underlying mechanisms of the cognitive deficits remain elusive. Repeated electroconvulsive shock (rECS) was used to simulate ECT and explore the mechanisms of ECT during the animal studies. Previous studies showed rECS could lead to neurogenesis and cognitive impairment. But it was well known that neurogenesis could improve the cognition. So these suggested that the mechanism of the cognitive deficit after rECS was very complex. In present study, we explored the probable mechanisms of the cognitive deficit after rECS from neurogenesis aspect. We found the cognitive deficit was reversible and neurogenesis could bring a long-term beneficial effect on cognition. Astrogliosis and NR1 down-regulation probably participated in the reversible cognitive deficits after rECS. Phenylbutyric acid (PBA), generally as an agent to investigate the roles of histone acetylation, could prevent the reversible cognitive dysfunction, but PBA could diminish the long-term effect of enhanced cognition by rECS. These suggested that ECT could possibly bring the long-term beneficial cognitive effect by regulating neurogenesis.

  14. The influence of personality and dysfunctional sleep-related cognitions on the severity of insomnia.

    Science.gov (United States)

    Park, Jang Ho; An, Hoyoung; Jang, Eun Sook; Chung, Seockhoon

    2012-05-30

    Previous findings suggest that personality traits and dysfunctional sleep-related cognitions may perpetuate insomnia, but findings concerning this have been scarce. Thus, we hypothesized that personality and sleep-related cognitions influence the severity of insomnia, and investigated the association personality and sleep-related cognitions had with various sleep-related parameters, including severity of insomnia. Forty-four patients with psychophysiological insomnia were assessed using The Temperament and Character Inventory, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Dysfunctional Belief and Attitudes toward Sleep Scale, the Pre-Sleep Arousal Scale and the Hospital Anxiety and Depression Scale. Insomnia severity was significantly and positively correlated with harm avoidance, self-transcendence and sleep-related cognitions, and negatively correlated with novelty seeking, reward dependence, and cooperativeness. Dysfunctional sleep-related cognitions were positively correlated with insomnia severity and sleep quality. Stepwise multiple regression analysis showed that sleep-related cognitions, depression and reward dependence scores were significant determinants of insomnia severity, and that sleep-related cognitions and self-transcendence were significant positive determinants of sleep quality. Reward dependence, depression and sleep-related cognitions were associated with insomnia severity, and comparison with previous findings implied that 'internalizing behavior' and depression may be more plausible candidates for the link between personality and insomnia than anxiety. Considering the major role of cognitive-behavioral treatment (CBT) in the treatment of insomnia, assessment of these factors and management of sleep-related cognitions may help alleviate symptoms in patients with insomnia.

  15. Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Sen Hee Tay

    2015-05-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS, collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE, remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients.

  16. Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Tay, Sen Hee; Mak, Anselm

    2015-05-06

    Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1-45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients.

  17. 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.

  18. Depression Is Associated with Cognitive Dysfunction in Older Adults with Heart Failure

    Directory of Open Access Journals (Sweden)

    Sarah Garcia

    2011-01-01

    Full Text Available Persons with heart failure (HF frequently exhibit cognitive impairment with deficits in attention and memory. Depression is common in HF though its possible contribution to cognitive impairment is unknown. Cognitive dysfunction and depression may share common mechanisms in HF, as both are associated with similar abnormalities on neuroimaging. A total of 116 participants with HF (68.53±9.30 years completed a neuropsychological battery and self-report measures of depression. Regression models showed depression incrementally and independently predicted test performance in all cognitive domains. Follow-up partial correlations revealed that greater depressive symptoms were associated with poorer performance on tests of attention, executive function, psychomotor speed, and language. These results indicate that depressive symptoms are associated with poorer cognitive performance in HF though further work is needed to clarify mechanisms for this association and possible cognitive benefits of treating depression in persons with HF.

  19. Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN Study): study protocol.

    Science.gov (United States)

    Takagi, Yasushi; Miyamoto, Susumu

    2015-01-01

    Moyamoya disease is a cerebrovascular occlusive disease characterized by progressive stenosis or by occlusion at the terminal portion of the bilateral internal carotid arteries. The unusual vascular network (moyamoya vessels) at the base of the brain with this disease as collateral channels is developed in this disease. Social independence because of cognitive impairment has recently been recognized as an important unsolved social issue with adult moyamoya disease. The patients with cognitive impairment have difficulty in proving their status because the standard neuroradiological and neuropsychological methods to define cognitive impairment with moyamoya disease are not determined. These patients with cognitive impairment should be supported by social welfare as psychologically handicapped persons. Thus Cognitive Dysfunction Survey of the Japanese Patients with Moyamoya Disease (COSMO-JAPAN study) is planned. In this study, we want to establish a standard finding of the cognitive impairment in patients with moyamoya disease.

  20. Modest Visceral Fat Gain Causes Endothelial Dysfunction In Healthy Humans

    Science.gov (United States)

    Romero-Corral, Abel; Sert-Kuniyoshi, Fatima H.; Sierra-Johnson, Justo; Orban, Marek; Gami, Apoor; Davison, Diane; Singh, Prachi; Pusalavidyasagar, Snigdha; Huyber, Christine; Votruba, Susanne; Lopez-Jimenez, Francisco; Jensen, Michael D.; Somers, Virend K.

    2014-01-01

    Objective This study sought to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study to assess the effects of fat gain on endothelial function. We recruited 43 normal weight healthy volunteers (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n=35) or to maintain weight (n=8). Endothelial function (brachial artery flow mediated dilation -FMD) was measured at baseline, after fat gain (8 weeks) and after weight loss (16 weeks) for fat-gainers and at baseline and follow-up (8 weeks) for weight-maintainers. Body composition was measured by DXA and abdominal CT scans. Results After an average weight gain of 4.1 kg, fat-gainers significantly increased their total, visceral and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight-maintainers. FMD decreased in fat-gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p =0.003), but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p=0.004), but not with subcutaneous fat gain (rho = −0.22, p=0.15). Conclusions In normal weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. PMID:20705223

  1. Could anemia be the reason for dysfunctional cognition???

    Directory of Open Access Journals (Sweden)

    Pranali S. Kharat

    2015-06-01

    Full Text Available Background: Studies claim that anemia at any time in life can hamper the metabolic processes and subsequently affect the cognitive and behavioral domain of an individual. Late-adolescent girls are one of the most vulnerable groups due to commencement of menstrual cycles, hormonal changes, nutritional deficits etc. It is also the time period where adolescents enter their professional careers in our country where cognition forms the basis of all the learning. This study was focused on seeing whether anemia affects the P300 wave which is a cognitive evoked potential. Methods: 74 girls of first and second year MBBS were chosen for this study. They were divided into two groups on basis of hemoglobin estimation by cyanmethemoglobin method. A comparative study was done of P300 latency and P300 amplitude between the two groups. Results: Comparison between the anemic group to the control group revealed: Latency of P300 was significantly delayed in the anemic group and amplitude was significantly higher in the control group. Conclusion: The results suggested a better cognitive performance of those having normal hemoglobin levels. [Int J Res Med Sci 2015; 3(3.000: 663-669

  2. 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.

  3. 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…

  4. 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

    PURPOSE To identify prevalence and associated factors of cognitive dysfunction in opioid-treated patients with cancer. PATIENTS AND METHODS EPOS (European Pharmacogenetic Opioid Study) is a prospective cross-sectional multicenter study in which adult patients with cancer who received treatment...

  5. 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.

    2015-01-01

    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 hypot

  6. High compliance to computerized tests for assessment of postoperative cognitive dysfunction

    NARCIS (Netherlands)

    Kok, W.F.; van Harten, A.E.; Scheeren, Thomas; Absalom, Anthony

    2012-01-01

    Background and Goal of Study: After cardiac surgery many patients experience postoperative cognitive dysfunction (POCD), usually comprising impaired concentration, attention, working memory and executive function. These sometimes subtle defects are usually assessed by neuropsychological examination,

  7. 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...

  8. The Possible Link between GABAergic Dysfunction and Cognitive Decline in a Patient with Idiopathic Hypoparathyroidism.

    Science.gov (United States)

    Terada, Tatsuhiro; Kakimoto, Akihiro; Yoshikawa, Etsuji; Kono, Satoshi; Bunai, Tomoyasu; Hosoi, Yasushi; Sakao-Suzuki, Makiko; Konishi, Takashi; Miyajima, Hiroaki; Ouchi, Yasuomi

    2015-01-01

    Idiopathic hypoparathyroidism (IHP) is accompanied by cognitive impairment. We report the case of a 70-year-old IHP patient with cognitive disturbance. Brain computed tomography showed bilateral calcification in basal ganglia, thalamus, and cerebellum. Neuropsychological assessment revealed low scores for intelligence, memory, and perseverative errors. Brain positron emission tomography showed a significant reduction in [(18)F]-Fludeoxyglucose (FDG) uptake in bilateral frontal, left temporal and parietal cortices, along with a marked reduction in [(11)C]-flumazenil binding in left frontal, temporal, parietal, and bilateral cerebellum. These findings suggest cognitive impairment in IHP may be ascribed to GABAergic dysfunction, thus leading to, or coexisting with, cerebral hypometabolism.

  9. 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

    BACKGROUND AND PURPOSE: The effects of single-nucleotide polymorphisms (SNPs) on the cognitive function of opioid-treated patients with cancer until now have not been explored, but they could potentially be related to poor functioning. This study aimed at identifying associations between SNPs...... of candidate genes, high opioid dose, and cognitive dysfunction. METHODS: Cross-sectional multicenter study (European Pharmacogenetic Opioid Study, 2005-2008); 1586 patients; 113 SNPs from 41 genes. INCLUSION CRITERIA: cancer, age ≥18 year, opioid treatment, and available genetic data. Cognitive assessment......-treated patients with cancer....

  10. Exposure to 1-bromopropane causes ovarian dysfunction in rats.

    Science.gov (United States)

    Yamada, Tetsuya; Ichihara, Gaku; Wang, Hailan; Yu, Xiaozhong; Maeda, Kei-ichiro; Tsukamura, Hiroko; Kamijima, Michihiro; Nakajima, Tamie; Takeuchi, Yasuhiro

    2003-01-01

    Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.

  11. [Association of PPARgamma2 Pro12Ala polymorphism and cognitive dysfunction in hypertension patients].

    Science.gov (United States)

    Peng, Yong; Luo, Xiao-jia; Chen, Xiao-ping; Li, Long-xin; Wan, Li-yan; He, Sen; Chen, Xiao-ni; Wu, Kai

    2010-11-01

    To study the relationship between PPARgamma2 Pro12Ala polymorphism and cognitive function in patients with primary hypertension. This study enrolled 502 hypertensive patients of Chinese Han population from Jan 2008 to Feb 2009 in West China Hospital of Sichuan University. We collected the general data and applied the mini mental state examination (MMSE) to test the cognitive function and computed score. Total cholesterol (TC), triglyeride (TG), fasting plasma glucose (FPG) and postprandial blood sugar (PPBS), fasting insulin (FINS) and postprandial plasma insulin (PINS) were measured. PCR-RELP method was used to analysis the PPARgamma2 Pro12Ala gene polymorphism. Pro12Pro genotype was present in 88.6% of the patients and Prol2Ala genotype was present in 11.4% of the population. Allele frequencies were 94.3% for Pro allele and 5.7% for Ala allele. In cognitive normal group, the frequencies of PP and PA genotype were 328 (87.2%) and 48 (12.8%), while the frequencies of PP and PA genotypes in the cognitive dysfunction group were 126 (92.9%), 9 (7.1%) respectively. Analyzed by chi2 test, both the genotype frequency and the allele frequency of PPARy2 Pro12Ala polymorphism did not display statistical variability between the cognitive normal group and the cognitive dysfunction group, even eliminating the influence of age and sexuality. Pro12Ala polymorphism in PPARgamma2 with primary hypertension may not associate with cognitive impairment.

  12. Diagnostic accuracy of a new instrument for detecting cognitive dysfunction in an emergent psychiatric population: the Brief Cognitive Screen.

    Science.gov (United States)

    Cercy, Steven P; Simakhodskaya, Zoya; Elliott, Aaron

    2010-03-01

    In certain clinical contexts, the sensitivity of the Mini-Mental State Examination (MMSE) is limited. The authors developed a new cognitive screening instrument, the Brief Cognitive Screen (BCS), with the aim of improving diagnostic accuracy for cognitive dysfunction in the psychiatric emergency department (ED) in a quick and convenient format. The BCS, consisting of the Oral Trail Making Test (OTMT), animal fluency, the Clock Drawing Test (CDT), and the MMSE, was administered to 32 patients presenting with emergent psychiatric conditions. Comprehensive neuropsychological evaluation served as the criterion standard for determining cognitive dysfunction. Diagnostic accuracy of the MMSE was determined using the traditional clinical cutoff and receiver operating characteristic (ROC) curve analyses. Diagnostic accuracy of individual BCS components and BCS Summary Scores was determined by ROC analyses. At the traditional clinical cutoff, MMSE sensitivity (46.4%) and total diagnostic accuracy (53.1%) were inadequate. Under ROC analyses, the diagnostic accuracy of the full BCS Summary Score (area under the curve [AUC]=0.857) was comparable to the MMSE (AUC=0.828). However, a reduced BCS Summary Score consisting of OTMT Part B (OTMT-B), animal fluency, and the CDT yielded classification accuracy (AUC=0.946) that was superior to the MMSE. Preliminary findings suggest the BCS is an effective, convenient alternative cognitive screening instrument for use in emergent psychiatric populations. Copyright (c) 2010 by the Society for Academic Emergency Medicine.

  13. 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.

  14. 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...

  15. Mitochondrial dysfunction in psychiatric and neurological diseases: cause(s), consequence(s), and implications of antioxidant therapy.

    Science.gov (United States)

    Kasote, Deepak M; Hegde, Mahabaleshwar V; Katyare, Surendra S

    2013-01-01

    Mitochondrial dysfunction is at the base of development and progression of several psychiatric and neurologic diseases with different etiologies. MtDNA/nDNA mutational damage, failure of endogenous antioxidant defenses, hormonal malfunction, altered membrane permeability, metabolic dysregulation, disruption of calcium buffering capacity and ageing have been found to be the root causes of mitochondrial dysfunction in psychatric and neurodegenerative diseases. However, the overall consequences of mitochondrial dysfunction are only limited to increase in oxidative/nitrosative stress and cellular energy crises. Thus far, extensive efforts have been made to improve mitochondrial function through specific cause-dependent antioxidant therapy. However, owing to complex genetic and interlinked causes of mitochondrial dysfunction, it has not been possible to achieve any common, unique supportive antioxidant therapeutic strategy for the treatment of psychiatric and neurologic diseases. Hence, we propose an antioxidant therapeutic strategy for management of consequences of mitochondrial dysfunction in psychiatric and neurologic diseases. It is expected that this will not only reduces oxidative stress, but also promote anaerobic energy production.

  16. A novel mutation in CACNA1A associated with hemiplegic migraine, cerebellar dysfunction and late-onset cognitive decline.

    Science.gov (United States)

    Freilinger, T; Ackl, N; Ebert, A; Schmidt, C; Rautenstrauss, B; Dichgans, M; Danek, A

    2011-01-15

    Hemiplegic migraine (HM) is a rare and severe subtype of migraine with aura, characterized by some degree of hemiparesis and other aura symptoms. Mutations in three genes (CACNA1A, ATP1A2 and SCN1A) have been detected in familial and, more rarely, in sporadic cases. The disease can be complicated by permanent neurological deficits, the most frequent one being a cerebellar syndrome; in addition, mental retardation has been recognized as part of the phenotypic spectrum. Here, we report a Caucasian male with a novel CACNA1A mutation and an unusual clinical phenotype: the patient, who had had a history of only two HM attacks, sought medical advice at age 49 primarily because of increasing cognitive decline accompanied by cerebellar dysfunction. While common neurodegenerative causes were excluded, neuropsychological evaluation revealed a distinct profile of deficits of a subcortico-prefrontal type as previously reported in patients with cerebellar dysfunction. This suggests a possible causal link between cerebellar and cognitive disturbances in this patient; in addition to these pathophysiological aspects, we review of the role of the cerebellum in cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Longitudinal study of cognitive dysfunctions induced by adjuvant chemotherapy in colon cancer patients.

    Science.gov (United States)

    Cruzado, Juan Antonio; López-Santiago, Sonia; Martínez-Marín, Virginia; José-Moreno, Gema; Custodio, Ana Belén; Feliu, Jaime

    2014-07-01

    Chemotherapy can induce cognitive impairment in cancer patients. The main goal of this longitudinal study was to determine the incidence, characteristics, and duration of cognitive dysfunction in patients treated with adjuvant chemotherapy for colon cancer. We assessed cognitive function, quality of life, anxiety and depression, fatigue, and hemoglobin levels in colon cancer patients at three assessment points: pre-chemotherapy (n=81), post-chemotherapy (n=73), and after 6-month follow-up (n=54). All patients were treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) for 6 months. Thirty patients (37%) had cognitive impairment in the pre-chemotherapy evaluation, mainly in processing speed and psychomotor executive function (Trail Making Test A and B). At the end of treatment, the main domain affected was the verbal memory, with an acute decline detected in 56% of patients. Fifty-four percent of the patients improved their dysfunction after 6 months of follow-up, whereas 18 (33%) of them showed worsening in at least one test. Cognitive impairment was most common in older patients and in those with less years of education. Quality of life, anxiety, depression, fatigue, and hemoglobin did not influence the results of the cognitive tests. Adjuvant FOLFOX4 in patients with colon cancer can have a negative effect on verbal memory. This deterioration is usually mild and transient.

  18. Cognitive Attentional Syndrome and Metacognitive Beliefs in Male Sexual Dysfunction: An Exploratory Study.

    Science.gov (United States)

    Giuri, Simona; Caselli, Gabriele; Manfredi, Chiara; Rebecchi, Daniela; Granata, Antonio; Ruggiero, Giovanni Maria; Veronese, Guido

    2016-06-08

    Erectile dysfunction (ED) and premature ejaculation (PE) are two forms of male sexual disorder with both psychological and physical features. While their cognitive, attentional, and affective components have been investigated separately, there is a lack of knowledge about the role played by cognitive attentional syndrome in their onset and maintenance. The aim of the present study was to investigate the possible contribution of perseverative thinking styles and thought control strategies to the development and maintenance of ED and PE. The authors hypothesized that such modes of processing might constitute a cognitive attentional syndrome specific to these disorders and sustained by particular metacognitive beliefs. A semistructured interview was administered to 11 participants with ED and 10 with PE in order to assess their metacognitive beliefs and cognitive attentional processes. The results suggest that individuals with ED and PE adopt a range of cognitive attentional strategies aimed at improving their sexual performance, and endorse both positive and negative metacognitive beliefs about these thinking responses. Overall, their cognitive and attentional patterns worsened negative internal states, reduced sexual excitement, detached them from their bodily sensations, and hindered sexual functioning. These preliminary findings suggest that perseverative thinking, thought control strategies, and metacognitive beliefs may play a key role in the onset and maintenance of male sexual dysfunction.

  19. Cognitive estimations as a measure of executive dysfunction in childhood epilepsy.

    Science.gov (United States)

    MacAllister, William S; Vasserman, Marsha; Coulehan, Kelly; Hall, Ari F; Bender, H Allison

    2016-01-01

    Children and adolescents with epilepsy are known to demonstrate executive function deficits. Despite prior work that has shown that cognitive estimation tasks are sensitive to executive dysfunction in children, such tasks have not been studied in children with epilepsy. This is particularly important given the fact that executive tasks have heretofore shown poor ecological validity, and it has been speculated that estimation tasks may show stronger ecological validity than other executive tests. One hundred and thirteen clinically referred children and adolescents with epilepsy were included. The Biber Cognitive Estimations Test was sensitive to cognitive dysfunction, with about half showing impairments on this task in comparison to age-matched normative data; the most frequently impaired subscales were quantity estimation and time estimation. Moreover, the Biber Cognitive Estimation Test showed moderate correlations with not only overall intellectual functions and academic achievement but also other commonly administered tests of executive functions, including digit span, Trailmaking, and the Tower of London but not with the contingency naming test. Cognitive estimations were also modestly correlated with age of epilepsy onset but not other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive Estimation Test would show strong ecological validity was not supported, as it showed weak relations with parent-reported executive function deficits. The significance and limitations of this investigation are discussed.

  20. 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.

  1. 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.

  2. Hypothalamic dysfunction without hamartomas causing gelastic seizures in optic nerve hypoplasia.

    Science.gov (United States)

    Fink, Cassandra; Borchert, Mark; Simon, Carrie Zaslow; Saper, Clifford

    2015-02-01

    This report describes gelastic seizures in patients with optic nerve hypoplasia and hypothalamic dysfunction without hypothalamic hamartoma. All participants (n = 4) from the optic nerve hypoplasia registry study at Children's Hospital Los Angeles presenting with gelastic seizures were included. The clinical and pathology characteristics include hypothalamic dysgenesis and dysfunction, but no hamartomas. Optic nerve hypoplasia is the only reported condition with gelastic seizures without hypothalamic hamartomas, suggesting that hypothalamic disorganization alone can cause gelastic seizures.

  3. 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

  4. Exendin-4 protected against cognitive dysfunction in hyperglycemic mice receiving an intrahippocampal lipopolysaccharide injection.

    Directory of Open Access Journals (Sweden)

    Hei-Jen Huang

    Full Text Available BACKGROUND: Chronic hyperglycemia-associated inflammation plays critical roles in disease initiation and the progression of diabetic complications, including Alzheimer's disease (AD. However, the association of chronic hyperglycemia with acute inflammation of the central nervous system in the progression of AD still needs to be elucidated. In addition, recent evidence suggests that Glucagon-like peptide-1 receptor (GLP-1R protects against neuronal damage in the brain. Therefore, the neuroprotective effects of the GLP-1R agonist exendin-4 (EX-4 against hyperglycemia/lipopolysaccharides (LPS damage were also evaluated in this study. METHODOLOGY/PRINCIPAL FINDINGS: Ten days after streptozotocin (STZ or vehicle (sodium citrate treatment in mice, EX-4 treatment (10 µg/kg/day was applied to the mice before intrahippocampal CA1 injection of LPS or vehicle (saline and continued for 28 days. This study examined the molecular alterations in these mice after LPS and EX4 application, respectively. The mouse cognitive function was evaluated during the last 6 days of EX-4 treatment. The results showed that the activation of NF-κB-related inflammatory responses induced cognitive dysfunction in both the hyperglycemic mice and the mice that received acute intrahippocampal LPS injection. Furthermore, acute intrahippocampal LPS injection exacerbated the impairment of spatial learning and memory through a strong decrease in monoaminergic neurons and increases in astrocytes activation and apoptosis in the hyperglycemic mice. However, EX-4 treatment protected against the cognitive dysfunction resulting from hyperglycemia or/and intrahippocampal LPS injection. CONCLUSIONS/SIGNIFICANCE: These findings reveal that both hyperglycemia and intrahippocampal LPS injection induced cognitive dysfunction via activation of NF-κB-related inflammatory responses. However, acute intrahippocampal LPS injection exacerbated the progression of cognitive dysfunction in the

  5. 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

    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......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...

  6. TERRA INCOGNITA - CEREBELLAR CONTRIBUTIONS TO NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION IN BEHAVIOURAL VARIANT FRONTOTEMPORAL DEMENTIA

    Directory of Open Access Journals (Sweden)

    Rachel H Tan

    2015-07-01

    Full Text Available Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioural variant frontotemporal dementia (bvFTD, a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function and motivation and the degree of grey matter degeneration in cerebellar lobules V-VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD.

  7. Upper extremity neuromotor dysfunction caused by local vibration

    Directory of Open Access Journals (Sweden)

    O. A. Shavlovskaya

    2015-01-01

    Full Text Available Vibration disease (VD (pneumatic hammer disease is a leader among occupational diseases. The prolonged use of vibrating tools is a high occupational health risk. The clinical picture of VD caused by local vibration includes sensorineural and upper extremity locomotor impairments that are polymorphic, polysyndromic, and not always specific. The International List of Occupational Diseases (2010 defines VD using the terms «vibration-induced white finger» (VWF and «hand-arm vibration syndrome» (HAVS. VWF as a manifestation of secondary Raynaud’s syndrome is the most noticeable vascular injury in HAVS. According to the recommendations of the International Labor Organization (2011 and the order of the Ministry of Health of Russia (2012, the clinical manifestations of local vibration include upper extremity polyneuropathy, secondary Raynaud’s phenomenon, and carpal tunnel syndrome (CTS. The paper considers approaches to differentially diagnosing CTS and HAVS, primary and secondary Raynaud’s syndrome, as well as clinical, laboratory, and electrodiagnostic studies. Prolonged exposure to vibration may affect the large myelinated (Ab fibers responsible for tactile touch, pressure, and vibration. Patients with VWF are frequently found to have hyperresponsiveness of the sympathetic nervous system, which affects digital vascular tone and appears as lower fingertip skin temperature. The paper discusses some possible mechanisms for the pathogenesis of vibration neuropathy (e.g. demyelinationof peripheral nerve fiber, as well as the involvement of plasma endothelin-1 in vascular response to cold as one of the components of the pathogenesis of vascular disorders. The central nervous system (cortical reorganization, plasticity phenomenon is believed to be implicated in the development and maintenance of vibration neuropathy.

  8. Executive Dysfunction Is the Primary Cognitive Impairment in Progressive Supranuclear Palsy

    Science.gov (United States)

    Gerstenecker, Adam; Mast, Benjamin; Duff, Kevin; Ferman, Tanis J.; Litvan, Irene

    2013-01-01

    Cognitive difficulties appear to be a more prevalent clinical feature in progressive supranuclear palsy (PSP) than previously thought, and significant cognitive impairment is prevalent in a majority of patients PSP patients not considered clinically demented. The neurocognitive performance of 200 patients with PSP across multiple sites was examined with a variety of commonly used neuropsychological tests. Results indicate primary executive dysfunction (e.g., 74% impaired on the Frontal Assessment Battery, 55% impaired on Initiation/Perseveration subscale of the Dementia Rating Scale), with milder difficulties in memory, construction, and naming. These results have important clinical implications for providers following patients with PSP. PMID:23127882

  9. An Observational Study with Long-Term Follow-Up of Canine Cognitive Dysfunction

    DEFF Research Database (Denmark)

    Fast, R.; Schutt, T.; Toft, N.

    2013-01-01

    Background: Canine cognitive dysfunction (CCD) is a neurodegenerative condition affecting geriatric dogs and sharing several characteristics with human Alzheimer's disease (AD). CCD manifests as alterations of behavioral patterns and daily routines. Clinical signs are associated with neurodegener......Background: Canine cognitive dysfunction (CCD) is a neurodegenerative condition affecting geriatric dogs and sharing several characteristics with human Alzheimer's disease (AD). CCD manifests as alterations of behavioral patterns and daily routines. Clinical signs are associated......, disorientation at home, and anxiety. A number of borderline CCD cases developed into CCD over time indicating that a prodromal stage of CCD may exist. CCD did not influence survival negatively. Small breeds did not show better survival than large breeds (P = .055) and there was no difference between sexes (P...

  10. 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.

  11. 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

  12. 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...

  13. Bipolar Disorder: Clinical Perspectives and Implications with Cognitive Dysfunction and Dementia

    Directory of Open Access Journals (Sweden)

    R. Lopes

    2012-01-01

    Full Text Available Introduction. Cognitive dysfunction as a core feature in the course of bipolar affective disorder (BPD is a current subject of debate and represents an important source of psychosocial and functional burden. Objectives. To stand out the connection and clinical implications between cognitive dysfunction, dementia, and BPD. Methods. A nonsystematic review of all English language PubMed articles published between 1995 and 2011 using the terms “bipolar disorder,” “cognitive dysfunction,” and “dementia”. Discussion. As a manifestation of an affective trait or stage, both in the acute phases and in remission, the domains affected include attention, executive function, and verbal memory. The likely evolution or overlap with the behavioural symptoms of an organic dementia allows it to be considered as a dementia specific to BPD. This is named by some authors, as BPD type VI, but others consider it a form of frontotemporal dementia. It is still not known if this process is neurodevelopmental or neurodegenerative in nature, or both simultaneously. The assessment should consider the iatrogenic effects of medication, the affective symptoms, and a neurocognitive evaluation. Conclusion. More specific neuropsychological tests and functional imaging studies are needed and will assume an important role in the near future for diagnosis and treatment.

  14. 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.

  15. 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...

  16. Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer's disease: the emerging role for microglia?

    Science.gov (United States)

    Piirainen, Sami; Youssef, Andrew; Song, Cai; Kalueff, Allan V; Landreth, Gary E; Malm, Tarja; Tian, Li

    2017-02-06

    Chronic psychosocial stress is increasingly recognized as a risk factor for late-onset Alzheimer's disease (LOAD) and associated cognitive deficits. Chronic stress also primes microglia and induces inflammatory responses in the adult brain, thereby compromising synapse-supportive roles of microglia and deteriorating cognitive functions during aging. Substantial evidence demonstrates that failure of microglia to clear abnormally accumulating amyloid-beta (Aβ) peptide contributes to neuroinflammation and neurodegeneration in AD. Moreover, genome-wide association studies have linked variants in several immune genes the expression of which in the brain is restricted to microglia, such as TREM2 and CR1, with cognitive dysfunctions in LOAD. Thus, inflammation-promoting chronic stress may create a vicious cycle of aggravated microglial dysfunction accompanied by increased Aβ accumulation, collectively exacerbating neurodegeneration. Surprisingly however, little is known about whether and how chronic stress contributes to microglia-mediated neuroinflammation that may underlie cognitive impairments in AD. This review aims to summarize the currently available clinical and preclinical data and outline potential molecular mechanisms linking stress, AD and neurodegeneration, to foster future research in this field.

  17. Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy.

    Science.gov (United States)

    Wu, Jing; Zhang, Mingqiang; Hao, Shuangying; Jia, Ming; Ji, Muhuo; Qiu, Lili; Sun, Xiaoyan; Yang, Jianjun; Li, Kuanyu

    2015-08-01

    Sepsis-associated encephalopathy (SAE) is associated with increased mortality, morbidity, and long-term cognitive impairments. Its pathophysiology remains to be determined and an effective pharmacologic treatment is lacking. The goal of this study was to investigate the effects of the mitochondria-targeted peptide SS-31 on mitochondrial function and cognitive deficits in SAE mice. C57BL/6 male mice were randomly divided into sham, sham + SS-31, cecal ligation and puncture (CLP), and CLP + SS-31 groups. Peptide SS-31 (5 mg/kg) was intraperitoneally administrated immediately after operation and afterwards once daily for six consecutive days. Surviving mice were subjected to behavioral tests and the hippocampus was collected for biochemical analysis 7 days after operation. The results showed that CLP resulted in high mortality rate and cognitive deficits, representative characteristics of SAE. A physiological mechanistic investigation revealed that mitochondrial function of hippocampus was severely impaired, coupled with reactive oxygen species (ROS) generation, triggering neuronal apoptosis and inflammation. Notably, administration of peptide SS-31 protected the integrity of mitochondria, reversed the mitochondrial dysfunction, inhibited the apoptosis resulting from the release of cytochrome c, diminished the response of inflammation, and ultimately reversed the behavior deficits in the SAE mice. In conclusion, our data demonstrate that daily treatment with mitochondria-targeted peptide SS-31 reduces mortality rate and ameliorates cognitive deficits, which is possibly through a mechanism of reversing mitochondrial dysfunction and partial inhibition of neuronal apoptosis and inflammation in the hippocampus of the SAE mice.

  18. 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

    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...... 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......, 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...

  19. Iron Metabolism Dysregulation and Cognitive Dysfunction in Pediatric Obesity: Is There a Connection?

    Science.gov (United States)

    Grandone, Anna; Marzuillo, Pierluigi; Perrone, Laura; Del Giudice, Emanuele Miraglia

    2015-11-06

    Obesity and iron deficiency (ID) are two of the most common nutritional disorders in the world. In children both conditions deserve particular attention. Several studies revealed an association between obesity and iron deficiency in children and, in some cases, a reduced response to oral supplementation. The connecting mechanism, however, is not completely known. This review is focused on: (1) iron deficiency in obese children and the role of hepcidin in the connection between body fat and poor iron status; (2) iron status and consequences on health, in particular on cognitive function; (3) cognitive function and obesity; (4) suggestion of a possible link between cognitive dysfunction and ID in pediatric obesity; and implications for therapy and future research.

  20. Iron Metabolism Dysregulation and Cognitive Dysfunction in Pediatric Obesity: Is There a Connection?

    Science.gov (United States)

    Grandone, Anna; Marzuillo, Pierluigi; Perrone, Laura; Miraglia del Giudice, Emanuele

    2015-01-01

    Obesity and iron deficiency (ID) are two of the most common nutritional disorders in the world. In children both conditions deserve particular attention. Several studies revealed an association between obesity and iron deficiency in children and, in some cases, a reduced response to oral supplementation. The connecting mechanism, however, is not completely known. This review is focused on: (1) iron deficiency in obese children and the role of hepcidin in the connection between body fat and poor iron status; (2) iron status and consequences on health, in particular on cognitive function; (3) cognitive function and obesity; (4) suggestion of a possible link between cognitive dysfunction and ID in pediatric obesity; and implications for therapy and future research. PMID:26561830

  1. 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

    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......, but also the number of peri-operative transfusions. The development of APOCD was also associated with impaired post-operative rehabilitation and an increased length of stay. APOCD was associated with the development of a major medical complication in 35% of all patients. In 65% of patients developing APOCD...

  2. Slow Progression of Cognitive Dysfunction of Alzheimer’s Disease in Sexagenarian Women with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Kazuo Sakai

    2015-01-01

    Full Text Available Although both schizophrenia (SCZ and Alzheimer’s disease (AD are among the most common psychiatric diseases, the interaction of these two is not well-understood. We investigated three women with SCZ who developed AD in their 60s. The patients presented with cognitive dysfunction such as loss of recent memory, which was confirmed by both clinical observations and neuropsychological tests. Their magnetic resonance and functional imaging findings were consistent with AD. Their brain atrophy advanced significantly during a 6-year observation period. However, their global cognitive function did not deteriorate significantly during this period. Although the cognitive reserve model might account for this discrepancy, our results suggest some interactions between the neuropathology of SCZ and AD and warrant further research.

  3. Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice.

    Science.gov (United States)

    Wang, Wei; Zhang, Xiao-Ying; Feng, Ze-Guo; Wang, Dong-Xin; Zhang, Hao; Sui, Bo; Zhang, Yong-Yi; Zhao, Wei-Xing; Fu, Qiang; Xu, Zhi-Peng; Mi, Wei-Dong

    2017-02-21

    Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments in patients after surgery. Hippocampal neuroinflammation induced by surgery is highly associated with POCD. Phosphodiesterase-4 (PDE4) is an enzyme that specifically hydrolyses cyclic adenosine monophosphate (cAMP), which plays an important role during neuroinflammation and the process of learning and memory. However, the role of PDE4 in the development of POCD remains unclear. Male 14-month-old C57BL/6 mice received carotid artery exposure to mimic POCD. First, we evaluated cognitive performance by a Morris water maze (MWM) and fear conditioning system (FCS) test after surgery. The expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were investigated. Then, we used rolipram, a PDE4 inhibitor, to block the effects of PDE4. The cognitive performance of the mice and the expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were examined again. Mice displayed learning and memory impairment, overexpression of PDE4B and PDE4D, elevation of pro-inflammatory cytokines, and reduction in the expression of p-CREB, PSD95 and cAMP levels after surgery. The expression of PDE4B and PDE4D in the hippocampus decreased following blocking of PDE4 by rolipram. Meanwhile, rolipram attenuated the cognitive impairment and the elevation of pro-inflammatory cytokines induced by surgery. Moreover, rolipram reversed the reduction of p-CREB and PSD95. These results indicate that PDE4 subtype overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. The significant effects of cerebral microbleeds on cognitive dysfunction: An updated meta-analysis.

    Science.gov (United States)

    Li, Xuanting; Yuan, Junliang; Yang, Lei; Qin, Wei; Yang, Shuna; Li, Yue; Fan, Huimin; Hu, Wenli

    2017-01-01

    Accumulated data suggests that cerebral microbleeds (CMBs) play an important role in the decline of cognitive function, but the results remain inconsistent. In the current study, we aimed to investigate the association between CMBs and cognitive function, as well as the various effects of CMBs on different domains of cognition. We searched through the databases of PubMed, Embase, Cochrane Library, and ScienceDirect. After a consistency test, the publication bias was evaluated and a sensitivity analysis was performed with combined odds ratios (OR) and standardized mean difference (SMD) of CMBs. A meta-analysis of 25 studies with 9343 participants total was conducted. Patients with CMBs had higher incidence of cognitive impairment (OR:3.5410; 95% confidence interval [CI] [2.2979, 5.4567], pCMBs had obvious decline in cognitive functions, for instance, orientation (SMD: -0.9565 [-1.7260, -0.1869], pCMBs might be an important risk factor for cognitive dysfunction, especially in the domains of orientation, attention and calculation and delayed recall functions. Prospective cohort studies with further investigations will be needed in larger samples.

  6. 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

  7. Role of Neurexin-1β and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats

    Science.gov (United States)

    Shen, Haitao; Chen, Zhouqing; Wang, Yang; Gao, Anju; Li, Haiying; Cui, Yonghua; Zhang, Li; Xu, Xiang; Wang, Zhong

    2015-01-01

    Background and Purpose— Neurexin-1β and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1β and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. Methods— In vivo, 228 Sprague–Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1β and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1β and neuroligin-1, as well as neurological outcome. Results— Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1β and neuroligin-1 and the interaction between neurexin-1β and neuroligin-1 in neurons. In addition, the interaction between neurexin-1β and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1β and neuroligin-1 and aggravated by the knockdown of neurexin-1β and neuroligin-1. More importantly, neurexin-1β and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1β and neuroligin-1 knockdown induced an opposite effect. Conclusions— Enhancing the expressions of neurexin-1β and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1β and neuroligin-1 might be good targets for improving cognitive function after SAH. PMID:26219651

  8. Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases.

    Science.gov (United States)

    Gibson, Gary E; Starkov, Anatoly; Blass, John P; Ratan, Rajiv R; Beal, M Flint

    2010-01-01

    Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sublethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post-transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the alpha-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhances ROS production in Alzheimer's Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington's Disease (HD), a movement disorder with cognitive features distinct form AD, complex II+III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium-activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a crosslinking enzymes that can modulate transcription, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic approaches

  9. 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.

  10. 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

  11. Quality of life in stable schizophrenia: the relative contributions of disorganization and cognitive dysfunction.

    Science.gov (United States)

    Sigaudo, Monica; Crivelli, Barbara; Castagna, Filomena; Giugiario, Michela; Mingrone, Cinzia; Montemagni, Cristiana; Rocca, Giuseppe; Rocca, Paola

    2014-03-01

    The purpose of this study was to examine the relative contributions of disorganization and cognitive dysfunction to quality of life (QOL) in patients with stable schizophrenia. A total of 276 consecutive outpatients with stable schizophrenia were enrolled in a cross-sectional study. We performed a mediation analysis to assess the specific effect of disorganization on QOL, as assessed by the Heinrichs-Carpenter Quality of Life Scale (QLS), and the possible mediating role of cognitive dysfunction. Our findings were as follows: (i) disorganization was negatively related to the total QLS score; (ii) disorganization was negatively related to two of the four QLS domains, namely the role-functioning domain (occupational/educational) and the intrapsychic functioning domain (e.g., motivation, curiosity, and empathy); and (iii) verbal memory was a partial mediator of the relationship between disorganization and QLS (the total score and the two above-mentioned domains). Disorganization demonstrated direct and indirect effects via verbal memory on two domains of functioning, as measured by the QLS. These results highlight the importance of improving disorganization and cognition (particularly verbal memory) to improve the functional outcomes of patients with schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 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 BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

  13. 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.

  14. Mechanism of blood-brain barrier impairment after mild traumatic brain injury caused by blast shock waves and its relationship with delayed nerve dysfunction

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    Zhao-xi XU

    2016-06-01

    Full Text Available Mild traumatic brain injury (mTBI caused by blast shock waves (BSWs is one of the most common injuries among soldiers in the war. Such mTBI can also happen in civilians if exposed to shock waves of accidental explosion disasters, bomb attacks by terrorists and so on. This injury often results in cognitive problems, memory dysfunction and emotional disorder, and these neurological deficits are closely related to the dysfunction or disruption of the blood-brain barrier (BBB. The present paper discusses mainly the relationship between dysfunction or disruption of BBB and inflammatory reaction in mild brain injury associated with explosive shock wave and effects of early intervention of oxidative stress injury, repairing the BBB and blocking inflammation on relieving delayed neurological deficits. DOI: 10.11855/j.issn.0577-7402.2016.05.15

  15. Diabetes type 2, hypertension and cognitive dysfunction in middle age women.

    Science.gov (United States)

    Petrova, Marina; Prokopenko, Semen; Pronina, Elena; Mozheyko, Elena

    2010-12-15

    Type 2 diabetes mellitus and hypertension are two widely spread diseases among the adults that are known to be risk factors for vascular disease. They are highly related such that comorbidity is common. The purpose of the present study was to investigate the comorbid effects of type 2 diabetes and hypertension on cognitive decline. One hundred and thirteen patients with type 2 diabetes (women, age 56±7.4 years, diabetes duration 8±6.7 years, hypertension duration 13.4±7.7 years) were assessed for cognitive impairment (CI) in comparison with 27 diabetes patients without hypertension (women, age 53±7.45 years, diabetes duration 4.4±5.6 years), all non-demented at baseline. Patients were screened for cognitive dysfunction with the Mini Mental State Examination (MMSE), a clock-drawing test (CDT) and Frontal Assessment Battery (FAB). We assessed history of DM and hypertension by interview. 87% of women with diabetes and hypertension and 70% of normotensive diabetic patients had cognitive impairment (p=0.0282), of mild and subtle degree. The frequency of alterations in the FAB was higher in subjects with diabetes and hypertension (48%) compared to normotensive diabetic patients (26%) p=0.0402. Our results show that people with diabetes type 2 and hypertension demonstrate greater cognitive changes as compared to normotensive diabetic patients.

  16. Determinants of Functional Disability in Huntington’s Disease: Role of Cognitive and Motor Dysfunction

    Science.gov (United States)

    Ross, Christopher A.; Pantelyat, Alex; Kogan, Jane; Brandt, Jason

    2014-01-01

    The clinical syndrome of Huntington’s disease is notable for a triad of motor, cognitive and emotional features. All HD patients eventually become occupationally disabled; however the factors that render HD patients unable to maintain employment have not been extensively studied. This review begins by discussing the clinical triad of HD, highlighting the distinction in the motor disorder between involuntary movements such as chorea, and voluntary movement impairment, with the latter contributing more to functional disability. Cognitive disorder clearly contributes to disability, though the relative contribution compared to motor is difficult to unravel, especially since many of the tests used to asses “cognition” have a strong motor component. The role of emotional changes in disability needs more study. The literature on contributions to functional disability, driving impairment and nursing home placement is reviewed. Relevant experience is presented from the longstanding JHU HD observational study on motor vs cognitive onset, and on cognitive and motor features at the time when individuals discontinued working. Finally, we briefly review government policies in several countries on disability determination. We interpret the data from our own studies and from the literature to indicate that there is usually a close relationship between cognitive and motor dysfunction, and that it is critical to take both into consideration in determining disability. PMID:25216368

  17. Combination of Spirulina with glycyrrhizin prevents cognitive dysfunction in aged obese rats.

    Science.gov (United States)

    Madhavadas, Sowmya; Subramanian, Sarada

    2015-01-01

    To evaluate the cognition enhancing effect of the combination of Spirulina and glycyrrhizin in monosodium glutamate (MSG)-induced obese aged rats. Obesity was induced in rats by administration of MSG (intraperitoneally, 4 mg/g body weight) for 14 consecutive days from day 1 after birth. Subsequently, the animals were allowed to grow for 18 months with food and water ad libitum. Hypercholesterolemia, hyperglycemia, leptin resistance, were monitored in these animals. Cognitive status was assessed by Barne's maze task and hippocampal acetylcholinesterase (AChE) levels. Further, the animals were treated with Spirulina (Sp) (oral route, 1 g/Kg body weight, for 30 days) alone or glycyrrhizin (Gly) alone (intraperitoneal route, 0.1 mg/Kg, on day 15 and day 21), or their combination (SpGly). Counting of the treatment days was done by considering first day of Sp administration as day 1. After the completion of 30 days of Spirulina treatment or 2 doses of Gly administration or the combination (SpGly) treatment, the animals were left for 3 weeks. They were then were assessed for their biochemical and cognitive changes. The combination of Sp with Gly showed a significant reduction (P < 0.0001) in glucose, cholesterol, leptin levels in the serum with improvement in cognitive functions with concomitant reduction in AChE activity in the hippocampal tissue homogenates (P < 0.0001) of the obese rats. SpGly combination has a potential role in reversing cognitive dysfunctions associated with aging and obesity.

  18. 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.

  19. Involvement of decreased neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats.

    Science.gov (United States)

    Guo, Ying; Yuan, Hua; Jiang, Lulu; Yang, Junlin; Zeng, Tao; Xie, Keqin; Zhang, Cuili; Zhao, Xiulan

    2015-03-10

    1-Bromopropane (1-BP) is used as a substitute for ozone-depleting solvents (ODS) in industrial applications. 1-BP could display central nervous system (CNS) neurotoxicity manifested by cognitive dysfunction. Neuroglobin (Ngb) is an endogenous neuroprotectant and is predominantly expressed in the nervous system. The present study aimed to investigate Ngb involvement in CNS neurotoxicity induced by 1-BP in rats. Male Wistar rats were randomly divided into 5 groups (n=14) and treated with 0, 100, 200, 400 and 800 mg/kg bw 1-BP, respectively, by gavage for consecutive 12 days. Rats displayed cognitive dysfunction dose-dependently through Morris water maze (MWM) test. Significant neuron loss in layer 5 of the prelimbic cortex (PL) was observed. Moreover, 1-BP decreased Ngb protein level in cerebral cortex and Ngb decrease was significantly positively correlated with cognitive dysfunction. Glutathione (GSH) content, GSH/oxidized glutathione (GSSG) ratio and glutamate cysteine ligase (GCL) activity decreased in cerebral cortex, coupled with the increase in GSSG content. GSH and GSH/GSSG ratio decrease were significantly positively correlated with cortical Ngb decrease. Additionally, levels of N-epsilon-hexanoyl-lysine (HEL) and 4-hydroxy-2-nonenal (4-HNE) modified proteins in cerebral cortex of 1-BP-treated rats increased significantly. In conclusion, it was suggested that 1-BP resulted in decreased endogenous neuroprotectant Ngb in cerebral cortex, which might play an important role in CNS neurotoxicity induced by 1-BP and that 1-BP-induced oxidative stress in cerebral cortex might partly be responsible for Ngb decrease.

  20. 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.

  1. 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

    Dementia and type 2 diabetes are both characterized by long prodromal phases challenging the study of potential risk factors and their temporal relation. The progressive relation between metabolic syndrome, insulin resistance, and dementia has recently been questioned, wherefore the aim...... of this study was to assess the potential association between these precursors of type 2 diabetes and cognitive dysfunction. Using data from the Prospective Epidemiological Risk Factor study (n=2,103), a prospective study of elderly women in Denmark, we found that impaired fasting plasma glucose was associated...

  2. Assessment of renal dysfunction using urinary markers in canine babesiosis caused by Babesia rossi.

    Science.gov (United States)

    Defauw, P; Schoeman, J P; Smets, P; Goddard, A; Meyer, E; Liebenberg, C; Daminet, S

    2012-12-21

    Renal damage is deemed a common, yet poorly documented, complication in canine babesiosis. Serum urea and creatinine are insensitive and non-specific markers of early renal dysfunction and their measurements are influenced by hemolysis caused by babesiosis. Therefore, the aim of this study was to use urinary markers to assess the localization and degree of renal dysfunction in dogs with Babesia rossi infection. Urinary immunoglobulin G (uIgG) and urinary C-reactive protein (uCRP) were measured as markers for glomerular dysfunction, while urinary retinol-binding protein (uRBP) was used as a marker for tubular dysfunction. Eighteen dogs presenting with uncomplicated babesiosis were included and compared with eight clinically healthy dogs. Previously validated commercial ELISA kits were used for the measurement of uIgG, uCRP, and uRBP. Results were related to urinary creatinine concentrations (c). Dogs with babesiosis had significantly higher concentrations of all three measured urinary markers compared to healthy dogs. Except for urinary protein/c ratio (UPC), routine urinary and serum markers for renal function (urine specific gravity (USG), serum urea and creatinine (sCr)) were not significantly different between dogs with babesiosis and healthy dogs. All three urinary markers were positively correlated with each other and with UPC. The data supports the presence of both glomerular and tubular dysfunction in dogs suffering from uncomplicated B. rossi infection. Urinary markers were superior to USG, serum urea and creatinine concentrations for the early detection of renal dysfunction in dogs with babesiosis.

  3. Cognitive dysfunction at baseline predicts symptomatic 1-year outcome in first-episode schizophrenics.

    Science.gov (United States)

    Moritz, S; Krausz, M; Gottwalz, E; Lambert, M; Perro, C; Ganzer, S; Naber, D

    2000-01-01

    The present study addresses the consequences of cognitive disturbances on symptomatic outcome. Fifty-three first-episode schizophrenics were reassessed (n = 32) 1 year after admission. Simple regression analyses revealed that several self-perceived cognitive deficits at baseline as measured with the Frankfurt Complaint Questionnaire significantly predicted increased Brief Psychiatric Rating Scale global scores at follow-up (p = 0.05 to p = 0.005). A stepwise regression analysis proved memory dysfunction to be the strongest predictor of symptomatic worsening (p = 0.005). It is suggested that the exploration and treatment of neuropsychological deficits in schizophrenia is of great clinical importance with regard to its impact on both functional and symptomatic outcome in schizophrenia. Copyright 2000 S. Karger AG, Basel

  4. The function of point injection in improving learning and memory dysfunction caused by cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Chen Hua-De

    2001-02-01

    Full Text Available This experiment has investigated the influence of Yamen (Du. 15 point injection on learning and memory dysfunction caused by cerebral ischemia and reprofusion in bilateral cervical general artery combined with bleeding on mouse tail to mimic vascular dementia in human beings. By dividing 40 mice into 4 groups (group1false operation group, group2model group, group3point injection with Cerebrolysin group4point injection with saline. According to random dividing principles, we observed the influence of Yamen(Du. 15 point injection on the time of swimming the whole course used by model mice which had received treatment for different days in different groups, and the influence of those mice on wrong times they entered blind end. The result showed that point injection with Cerebrolysin and saline could improve learning and memory dysfunction of the mice caused by cerebral ischemia.

  5. Arecoline cannot alter testicular dysfunction and pineal activation caused by noise in wistar rat.

    Science.gov (United States)

    Saha, Indraneel; Chatterjee, Aniruddha; Chatterji, Urmi; Maiti, B R

    2017-07-13

    Millions of people consume betel nut for increased capacity to work and for stress reduction. The nut contains arecoline, which has multiple side effects on endocrine functions. Objective of the work is to investigate pineal-testicular responses to noise and after arecoline treatment in noise in rats. Noise exposure (100 dB, 6 h daily, 10 days) caused pineal stimulation ultrastructurally and at indoleamines level. Leydig cell dysfunction with fall of testosterone level and suppression of sex accessories were noticed. In contrast, pineal activity was inhibited and reproductive functions were stimulated after arecoline administration, confirmed from reversed changes to those of noise. Arecoline treatment in noise exposure showed same results as in noise both in pineal and in reproductive functions. It is concluded that noise causes testicular dysfunction probably by gonadotropin suppression induced by pineal melatonin in noise. Furthermore, arecoline cannot prevent it in noise in rats.

  6. Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder.

    Science.gov (United States)

    Breakspear, Michael; Roberts, Gloria; Green, Melissa J; Nguyen, Vinh T; Frankland, Andrew; Levy, Florence; Lenroot, Rhoshel; Mitchell, Philip B

    2015-11-01

    The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder. © The Author (2015). Published by Oxford University Press on behalf

  7. 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.

  8. 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.

  9. Effects of ketoprofen for prevention of postoperative cognitive dysfunction in aged rats.

    Science.gov (United States)

    Kawano, Takashi; Takahashi, Tetsuya; Iwata, Hideki; Morikawa, Akihiro; Imori, Satoko; Waki, Sayaka; Tamura, Takahiko; Yamazaki, Fumimoto; Eguchi, Satoru; Kumagai, Naoko; Yokoyama, Masataka

    2014-12-01

    Postoperative cognitive dysfunction is a common geriatric complication that may be associated with increased mortality. Here, we investigated the effects of postoperative analgesia with ketoprofen on cognitive functions in aged animals and compared its effectiveness to morphine. Rats were randomly allocated to one of four groups: isoflurane anesthesia without surgery (group C), isoflurane anesthesia with laparotomy (group IL), and isoflurane anesthesia with laparotomy plus postoperative analgesia with ketoprofen or morphine. There was no difference in postoperative locomotor activity among groups. In group IL, postoperative pain levels assessed by the Rat Grimace Scale significantly increased until 8 h after surgery, which was similarly inhibited by both ketoprofen and morphine. Cognitive function was assessed using radial arm maze testing for 12 consecutive days from postoperative day 3. Results showed that the number of memory errors in group IL were significantly higher than those in goup C. However, both ketoprofen and morphine could attenuate the increase in memory errors following surgery to a similar degree. Conversely, ketoprofen showed no effect on cognitive function in the nonsurgical rats that did not experience pain. Our findings suggest that postoperative analgesia with ketoprofen can prevent the development of surgery-associated memory deficits via its pain-relieving effects.

  10. Treatment of Cognitive Impairment in Schizophrenia: Potential Value of Phosphodiesterase Inhibitors in Prefrontal Dysfunction.

    Science.gov (United States)

    Duinen, Marlies Van; Reneerkens, Olga A H; Lambrecht, Lena; Sambeth, Anke; Rutten, Bart P F; Os, Jim Van; Blokland, Arjan; Prickaerts, Jos

    2015-01-01

    No pharmacological treatment is available to date that shows satisfactory effects on cognitive symptoms in patients diagnosed with schizophrenia. Phosphodiesterase inhibitors (PDE-Is) improve neurotransmitter signaling by interfering in intracellular second messenger cascades. By preventing the breakdown of cAMP and/or cGMP, central neurotransmitter activity is maintained. Different PDE families exist with distinct characteristics among which substrate specificity and regional distribution. Preclinical data is promising especially with regard to inhibition of PDE2, PDE4, PDE5 and PDE10. In addition, cognitive improvement has been reported in both elderly and/or non-impaired young human subjects after PDE1 or PDE4 inhibition. Moreover, some of these studies show effects on cognitive domains relevant to schizophrenia, in particular memory. The current review incorporates an overview of the distinct molecular characteristics of the different PDE families and their relationship to the neurobiological mechanisms related to cognitive dysfunction in schizophrenia. So far, procognitive effects of only three types of PDE-Is have been assessed in patients diagnosed with schizophrenia inhibiting PDE3, PDE5 and PDE10. However, the limited data available do not allow to draw firm conclusions on the value of PDE-Is as cognitive enhancers in schizophrenia yet. The field is still in its infancy, but nevertheless different PDE-Is seem promising as candidate to optimise neural communication in the prefrontal cortex favouring cognitive functioning in patients diagnosed with schizophrenia, in particular dual inhibitors including PDE1-Is, PDE3-Is and PDE10A-Is.

  11. Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer diseases.

    Science.gov (United States)

    Mattis, Paul J; Niethammer, Martin; Sako, Wataru; Tang, Chris C; Nazem, Amir; Gordon, Marc L; Brandt, Vicky; Dhawan, Vijay; Eidelberg, David

    2016-11-01

    To determine whether cognitive impairment in Parkinson disease (PD) and Alzheimer disease (AD) derives from the same network pathology. We analyzed (18)F-fluorodeoxyglucose PET scans from 40 patients with AD and 40 age-matched healthy controls from the Alzheimer's Disease Neuroimaging Initiative and scanned an additional 10 patients with AD and 10 healthy controls at The Feinstein Institute for Medical Research to derive an AD-related metabolic pattern (ADRP) analogous to our previously established PD cognition-related pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual subject expression values for ADRP and PDCP in 89 patients with PD and correlated summary scores for cognitive functioning with network expression. We also evaluated changes in ADRP and PDCP expression in a separate group of 15 patients with PD scanned serially over a 4-year period. Analysis revealed a significant AD-related metabolic topography characterized by covarying metabolic reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal association regions. Expression of ADRP, but not PDCP, was elevated in both AD groups and correlated with worse cognitive summary scores. Patients with PD showed slight ADRP expression, due to topographic overlap with the network underlying PD motor-related pattern degeneration, but only their PDCP expression values increased as cognitive function and executive performance declined. Longitudinal data in PD disclosed an analogous dissociation of network expression. Cognitive dysfunction in PD is associated with a specific brain network that is largely spatially and functionally distinct from that seen in relation to AD. © 2016 American Academy of Neurology.

  12. 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.

  13. Apathy, cognitive dysfunction and impaired social cognition in a patient with bilateral thalamic infarction.

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    Ioannidis, Anestis E; Kimiskidis, Vasilios K; Loukopoulou, Eleni; Geroukis, Triantafyllos; Vlaikidis, Nikolaos; Kosmidis, Mary H

    2013-01-01

    We describe the case of a patient with bilateral thalamic lesions due to brain infarcts in the paramedian thalamic artery territories. The patient demonstrated symptoms of apathy (e.g., loss of initiative and interest in others, poor motivation, flattened affect). Neuropsychological assessment 3 and 5 years post-infarct revealed severe deficits in verbal and non-verbal immediate and delayed memory, attention, and executive functioning, with minimal improvement over time. Also, he demonstrated difficulties in social cognition (i.e., perception of facial expressions of others and of sarcasm). These findings are discussed and interpreted in light of current theories regarding the neurobiological substrate of apathy.

  14. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.

    Science.gov (United States)

    De Filippis, Bianca; Valenti, Daniela; Chiodi, Valentina; Ferrante, Antonella; de Bari, Lidia; Fiorentini, Carla; Domenici, Maria Rosaria; Ricceri, Laura; Vacca, Rosa Anna; Fabbri, Alessia; Laviola, Giovanni

    2015-06-01

    Rho GTPases are molecules critically involved in neuronal plasticity and cognition. We have previously reported that modulation of brain Rho GTPases by the bacterial toxin CNF1 rescues the neurobehavioral phenotype in MeCP2-308 male mice, a model of Rett syndrome (RTT). RTT is a rare X-linked neurodevelopmental disorder and a genetic cause of intellectual disability, for which no effective therapy is available. Mitochondrial dysfunction has been proposed to be involved in the mechanism of the disease pathogenesis. Here we demonstrate that modulation of Rho GTPases by CNF1 rescues the reduced mitochondrial ATP production via oxidative phosphorylation in the brain of MeCP2-308 heterozygous female mice, the condition which more closely recapitulates that of RTT patients. In RTT mouse brain, CNF1 also restores the alterations in the activity of the mitochondrial respiratory chain (MRC) complexes and of ATP synthase, the molecular machinery responsible for the majority of cell energy production. Such effects were achieved through the upregulation of the protein content of those MRC complexes subunits, which were defective in RTT mouse brain. Restored mitochondrial functionality was accompanied by the rescue of deficits in cognitive function (spatial reference memory in the Barnes maze), synaptic plasticity (long-term potentiation) and Tyr1472 phosphorylation of GluN2B, which was abnormally enhanced in the hippocampus of RTT mice. Present findings bring into light previously unknown functional mitochondrial alterations in the brain of female mice modeling RTT and provide the first evidence that RTT brain mitochondrial dysfunction can be rescued by modulation of Rho GTPases.

  15. 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.

  16. Paget's disease of the skull causing hyperprolactinemia and erectile dysfunction: a case report

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    Hepherd Rachel

    2008-07-01

    Full Text Available Abstract Introduction Hyperprolactinemia is an uncommon cause of erectile dysfunction in men. Paget's disease of the skull is a relatively common disease. This case proposes a rare example of a causative link between the two and how treatment of the Paget's disease with bisphosphonates helped the patient regain erectile function. Case presentation A 67-year-old man with Paget's disease of the skull presented with prostatitis, erectile dysfunction, and hyperprolactinemia. Radio-isotope scanning showed increased vascularity around the sphenoid bone. Treatment with intravenous bisphosphonates improved the active Paget's disease as indicated by declining alkaline phosphatase levels and the patient's erectile function while serum prolactin levels became normal and serum testosterone levels remained unchanged. Conclusion It is possible that hyperprolactinemia is unrecognised in other patients with Paget's disease of the skull. Normalizing elevated prolactin levels by using bisphosphonates in treating Paget's disease appears to be more appropriate than traditional treatment for hyperprolactinemia.

  17. 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.

  18. Functional correlates of cognitive dysfunction in multiple sclerosis: A multicenter fMRI Study.

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    Rocca, Maria A; Valsasina, Paola; Hulst, Hanneke E; Abdel-Aziz, Khaled; Enzinger, Christian; Gallo, Antonio; Pareto, Debora; Riccitelli, Gianna; Muhlert, Nils; Ciccarelli, Olga; Barkhof, Frederik; Fazekas, Franz; Tedeschi, Gioacchino; Arévalo, Maria J; Filippi, Massimo

    2014-12-01

    In this multicenter study, we applied functional magnetic resonance imaging (fMRI) to define the functional correlates of cognitive dysfunction in patients with multiple sclerosis (MS). fMRI scans during the performance of the N-back task were acquired from 42 right-handed relapsing remitting (RR) MS patients and 52 sex-matched right-handed healthy controls, studied at six European sites using 3.0 Tesla scanners. Patients with at least two abnormal (<2 standard deviations from the normative values) neuropsychological tests at a standardized evaluation were considered cognitively impaired (CI). FMRI data were analyzed using the SPM8 software, modeling regions showing load-dependent activations/deactivations with increasing task difficulty. Twenty (47%) MS patients were CI. During the N-back load condition, compared to controls and CI patients, cognitively preserved (CP) patients had increased recruitment of the right dorsolateral prefrontal cortex. As a function of increasing task difficulty, CI MS patients had reduced activations of several areas located in the fronto-parieto-temporal lobes as well as reduced deactivations of regions which are part of the default mode network compared to the other two groups. Significant correlations were found between abnormal fMRI patterns of activations and deactivations and behavioral measures, cognitive performance, and brain T2 and T1 lesion volumes. This multicenter study supports the theory that a preserved fMRI activity of the frontal lobe is associated with a better cognitive profile in MS patients. It also indicates the feasibility of fMRI to monitor disease evolution and treatment effects in future studies.

  19. Combination of Spirulina with glycyrrhizin prevents cognitive dysfunction in aged obese rats

    Science.gov (United States)

    Madhavadas, Sowmya; Subramanian, Sarada

    2015-01-01

    Objectives: To evaluate the cognition enhancing effect of the combination of Spirulina and glycyrrhizin in monosodium glutamate (MSG)-induced obese aged rats. Materials and Methods: Obesity was induced in rats by administration of MSG (intraperitoneally, 4 mg/g body weight) for 14 consecutive days from day 1 after birth. Subsequently, the animals were allowed to grow for 18 months with food and water ad libitum. Hypercholesterolemia, hyperglycemia, leptin resistance, were monitored in these animals. Cognitive status was assessed by Barne's maze task and hippocampal acetylcholinesterase (AChE) levels. Further, the animals were treated with Spirulina (Sp) (oral route, 1 g/Kg body weight, for 30 days) alone or glycyrrhizin (Gly) alone (intraperitoneal route, 0.1 mg/Kg, on day 15 and day 21), or their combination (SpGly). Counting of the treatment days was done by considering first day of Sp administration as day 1. After the completion of 30 days of Spirulina treatment or 2 doses of Gly administration or the combination (SpGly) treatment, the animals were left for 3 weeks. They were then were assessed for their biochemical and cognitive changes. Results: The combination of Sp with Gly showed a significant reduction (P < 0.0001) in glucose, cholesterol, leptin levels in the serum with improvement in cognitive functions with concomitant reduction in AChE activity in the hippocampal tissue homogenates (P < 0.0001) of the obese rats. Conclusion: SpGly combination has a potential role in reversing cognitive dysfunctions associated with aging and obesity. PMID:25821309

  20. 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

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

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    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.

  2. Negative cognitive styles, dysfunctional attitudes, and the remitted depression paradigm: a search for the elusive cognitive vulnerability to depression factor among remitted depressives.

    Science.gov (United States)

    Haffel, Gerald J; Abramson, Lyn Y; Voelz, Zachary R; Metalsky, Gerald I; Halberstadt, Lisa; Dykman, Benjamin M; Donovan, Patricia; Hogan, Michael E; Hankin, Benjamin L; Alloy, Lauren B

    2005-09-01

    Results from studies using a behavioral high-risk design and approximations to it generally have corroborated the cognitive vulnerability hypothesis of depression, whereas results from remitted depression studies typically have not. Suspecting that design features of previously conducted remitted designs likely precluded them from detecting maladaptive cognitive patterns, the authors conducted a study featuring the remitted design that has been successful in studies of a biological vulnerability for depression. Participants' current depressive symptoms, negative cognitive styles (hopelessness theory), dysfunctional attitudes (Beck's theory), and lifetime prevalence of clinically significant depression were assessed. Participants who had remitted from an episode of clinically significant depression had more negative cognitive styles, but not greater levels of dysfunctional attitudes, than did never depressed individuals. ((c) 2005 APA, all rights reserved).

  3. Suberoylanilide Hydroxamic Acid, A Histone Deacetylase Inhibitor, Attenuates Postoperative Cognitive Dysfunction in Aging Mice

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    Min eJia

    2015-09-01

    Full Text Available Postoperative cognitive dysfunction (POCD is a recognized clinical entity characterized with cognitive deficits after anesthesia and surgery, especially in aged patients. Previous studies have shown that histone acetylation plays a key role in hippocampal synaptic plasticity and memory formation. However, its role in POCD remains to be determined. Here, we show that suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor, attenuates POCD in aging Mice. After exposed to the laparotomy, a surgical procedure involving an incision into abdominal walls to examine the abdominal organs, 16- but not 3-month old male C57BL/6 mice developed obvious cognitive impairments in the test of long-term contextual fear conditioning. Intracerebroventricular (i.c.v. injection of SAHA at the dose of (20 μg/2 μl 3 hours before and daily after the laparotomy restored the laparotomy-induced reduction of hippocampal acetyl-H3 and acetyl-H4 levels and significantly attenuated the hippocampus-dependent long-term memory impairments in 16-month old mice. SAHA also reduced the expression of cleaved caspase-3, inducible nitric oxide synthase and N-methyl-D-aspartate receptor-calcium/calmodulin dependent kinase II pathway, and increased the expression of brain-derived neurotrophic factor, synapsin 1, and postsynaptic density 95. Taken together, our data suggest that the decrease of histone acetylation contributes to POCD and may serve as a target to improve the neurological outcome of POCD.

  4. Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats

    Science.gov (United States)

    Kan, Min Hui; Yang, Ting; Fu, Hui Qun; Fan, Long; Wu, Yan; Terrando, Niccolò; Wang, Tian-Long

    2016-01-01

    Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure. PMID:27493629

  5. Juvenile Myoclonic Epilepsy (JME: Neuropsychological Profile and Related Factors with Cognitive Dysfunction.

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    Mahmood Motamedi

    2014-03-01

    Full Text Available The aim of present study was to verify possible cognitive dysfunction in the patients with Juvenile Myoclonic Epilepsy (JME and its correlation to factors related to epilepsy and patients demographic variables.Thirty two consecutive patients with JME and 32 healthy controls were evaluated in neuropsychological domains including orientation, mental control, logical memory, forward and backward digit spans, visual memory, associative learning, and memory quotient (using Persian version of Wechsler Memory Scale (WMS-Revised, preservative errors (using Wisconsin Card Sorting Test (WCST, Stroop Test (color and word, IQ score (using Raven's Progressive Matrices test, and depression (using the Persian version of Beck Depression Inventory (BDI. SPSS 11.0 (SPSS Inc., Chicago, Illinois, USA software was used for statistical analysis. Student's t-test and the Mann-Whitney U-test were used for independent normally and non-normally distributed continuous variables, respectively.Our study showed significant differences between patients with JME and control group with respect to scores of mental control (p=0.015, forward digit span (p=0.004, total digit span (p=0.008 and IQ (p=0.003. In addition, age, education level, duration of epilepsy and medication showed an impact on several cognitive functions in the patients with JME.It is indicated that JME is associated with impairment in specific cognitive domains, despite any evidence in favor of depression.

  6. 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.

  7. Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats.

    Science.gov (United States)

    Kan, Min Hui; Yang, Ting; Fu, Hui Qun; Fan, Long; Wu, Yan; Terrando, Niccolò; Wang, Tian-Long

    2016-01-01

    Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure.

  8. 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.

  9. Cognitive dysfunction in Body Dysmorphic Disorder: New implications for nosological systems & neurobiological models

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    Jefferies-Sewell, K; Chamberlain, SR; Fineberg, NA; Laws, KR

    2017-01-01

    Background Body dysmorphic disorder (BDD) is a debilitating disorder, characterised by obsessions and compulsions relating specifically to perceived appearance, newly classified within the DSM-5 Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder. Materials and Methods Participants with BDD (n=12) and healthy controls (n=16) were tested using a computerised neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task) and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ and education. Results In comparison to controls, patients with BDD showed significantly impaired attentional set shifting, abnormal decision-making, impaired response inhibition and greater omission and commission errors on the emotional processing task. Conclusions Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the re-classification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD. PMID:27899165

  10. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.

    Science.gov (United States)

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2015-10-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.

  11. 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.

  12. 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.

  13. 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.

  14. Long-term follow-up of cognitive dysfunction in patients with aluminum hydroxide-induced macrophagic myofasciitis (MMF).

    Science.gov (United States)

    Passeri, Elodie; Villa, Chiara; Couette, Maryline; Itti, Emmanuel; Brugieres, Pierre; Cesaro, Pierre; Gherardi, Romain K; Bachoud-Levi, Anne-Catherine; Authier, François-Jérôme

    2011-11-01

    Macrophagic myofasciitis (MMF) is characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. Representative features of MMF-associated cognitive dysfunction (MACD) include (i) dysexecutive syndrome; (i) visual memory; (iii) left ear extinction at dichotic listening test. In present study we retrospectively evaluated the progression of MACD in 30 MMF patients. Most patients fulfilled criteria for non-amnestic/dysexecutive mild cognitive impairment, even if some cognitive deficits seemed unusually severe. MACD remained stable over time, although dysexecutive syndrome tended to worsen. Long-term follow-up of a subset of patients with 3 or 4 consecutive neuropsychological evaluations confirmed the stability of MACD with time, despite marked fluctuations.

  15. Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway

    OpenAIRE

    Ramesh Vijay; Nair Deepti; Zhang Shelley X L; Hakim Fahed; Kaushal Navita; Kayali Foaz; Wang Yang; Li Richard C; Carreras Alba; Gozal David

    2012-01-01

    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...

  16. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings.

    Science.gov (United States)

    Gea, Joaquim; Pascual, Sergi; Casadevall, Carme; Orozco-Levi, Mauricio; Barreiro, Esther

    2015-10-01

    Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future.

  17. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings

    Science.gov (United States)

    Pascual, Sergi; Casadevall, Carme; Orozco-Levi, Mauricio; Barreiro, Esther

    2015-01-01

    Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future. PMID:26623119

  18. Mitochondrial polymerase gamma dysfunction and aging cause cardiac nuclear DNA methylation changes.

    Science.gov (United States)

    Koczor, Christopher A; Ludlow, Ivan; Fields, Earl; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Lewis, William

    2016-04-01

    Cardiomyopathy (CM) is an intrinsic weakening of myocardium with contractile dysfunction and congestive heart failure (CHF). CHF has been postulated to result from decreased mitochondrial energy production and oxidative stress. Effects of decreased mitochondrial oxygen consumption also can accelerate with aging. We previously showed DNA methylation changes in human hearts with CM. This was associated with mitochondrial DNA depletion, being another molecular marker of CM. We examined the relationship between mitochondrial dysfunction and cardiac epigenetic DNA methylation changes in both young and old mice. We used genetically engineered C57Bl/6 mice transgenic for a cardiac-specific mutant of the mitochondrial polymerase-γ (termed Y955C). Y955C mice undergo left ventricular hypertrophy (LVH) at a young age (∼ 94 days old), and LVH decompensated to CHF at old age (∼ 255 days old). Results found 95 genes differentially expressed as a result of Y955C expression, while 4,452 genes were differentially expressed as a result of aging hearts. Moreover, cardiac DNA methylation patterns differed between Y955C (4,506 peaks with 68.5% hypomethylation) and aged hearts (73,286 peaks with 80.2% hypomethylated). Correlatively, of the 95 Y955C-dependent differentially expressed genes, 30 genes (31.6%) also displayed differential DNA methylation; in the 4,452 age-dependent differentially expressed genes, 342 genes (7.7%) displayed associated DNA methylation changes. Both Y955C and aging demonstrated significant enrichment of CACGTG-associated E-box motifs in differentially methylated regions. Cardiac mitochondrial polymerase dysfunction alters nuclear DNA methylation. Furthermore, aging causes a robust change in cardiac DNA methylation that is partially associated with mitochondrial polymerase dysfunction. Copyright © 2016 the American Physiological Society.

  19. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  20. The anti-cancer drug, doxorubicin, causes oxidant stress-induced endothelial dysfunction.

    Science.gov (United States)

    Wolf, Matthew B; Baynes, John W

    2006-02-01

    The anticancer drug doxorubicin (DOX) is toxic to target cells, but also causes endothelial dysfunction and edema, secondary to oxidative stress in the vascular wall. Thus, the mechanism of action of this drug may involve chemotoxicity to both cancer cells and to the endothelium. Indeed, we found that the permeability of monolayers of bovine pulmonary artery endothelial cells (BPAEC) to albumin was increased by approximately 10-fold above control, following 24-h exposure to clinically relevant concentrations of DOX (up to 1 microM). DOX also caused >4-fold increases in lactate dehydrogenase leakage and large decreases in ATP and reduced glutathione (GSH) in BPAECs, which paralleled the increases in endothelial permeability. A large part of the ATP loss could be attributed to DOX-induced hydrogen peroxide production which inhibited key thiol-enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate dehydrogenase (G6PDH). Depletion of reduced nicotinamide adenine dinucleotide phosphate (NADPH) appeared to be a major factor leading to DOX-induced GSH depletion. At low concentrations, the sulfhydryl reagent, iodoacetate (IA), inhibited GAPDH, caused a decrease in ATP and increased permeability, without inhibiting G6PDH or decreasing GSH. These results, coupled with those of previous work on a related quinone, menadione, suggest that depletion of either GSH or ATP may lead independently to endothelial dysfunction during chemotherapy, contributing to the cardiotoxicity and other systemic side-effects of the drug.

  1. Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.

    Science.gov (United States)

    Zheng, Bin; Lai, Renchun; Li, Jun; Zuo, Zhiyi

    2017-03-01

    Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane. They were tested by Barnes maze and fear conditioning from 2weeks after the surgery. Hippocampus was harvested 6h, 24h and 7days after the surgery for immunohistochemical staining and Western blotting. Mice with surgery under anesthesia with isoflurane, sevoflurane or desflurane took longer than control mice to identify the target box 1 or 8days after the training sessions in Barnes maze. Mice anesthetized by isoflurane or sevoflurane, but not by desflurane, had less freezing behavior than control mice in fear conditioning test. Mice with surgery and anesthesia had increased ionized calcium binding adapter molecule 1 and interleukin 1β in the hippocampus but this increase was smaller in mice anesthetized with desflurane than mice anesthetized with isoflurane. Mice with surgery had increased P2X7 receptors and its downstream molecule caspase 1. Inhibition or knockout of P2X7 receptors attenuated surgery and anesthesia-induced neuroinflammation and cognitive impairment. We conclude that surgery under desflurane anesthesia may have reduced neuroinflammation and cognitive impairment compared with surgery under isoflurane anesthesia. P2X7 receptors may mediate the neuroinflammation and cognitive impairment after surgery.

  2. 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.

  3. The association between insomnia-related sleep disruptions and cognitive dysfunction during the inter-episode phase of bipolar disorder.

    Science.gov (United States)

    Kanady, Jennifer C; Soehner, Adriane M; Klein, Alexandra B; Harvey, Allison G

    2017-05-01

    Sleep disturbance and cognitive dysfunction are two domains of impairment during inter-episode bipolar disorder. Despite evidence demonstrating the importance of sleep for cognition in healthy and sleep-disordered samples, this link has been minimally examined in bipolar disorder. The present study tested the association between insomnia-related sleep disruptions and cognitive dysfunction during inter-episode bipolar disorder. Forty-seven participants with bipolar disorder and a comorbid insomnia diagnosis (BD-Insomnia) and 19 participants with bipolar disorder without sleep disturbance in the last six months (BD-Control) participated in the study. Two domains of cognition were assessed: working memory and verbal learning. Insomnia-related sleep disruptions were assessed both categorically (i.e., insomnia diagnosis) and dimensionally (i.e., total wake time, total sleep time, total wake time variability, and total sleep time variability). Hierarchical linear regressions, adjusting for participant age, demonstrated that insomnia diagnosis did not have an independent or interactive effect on cognition. However, regardless of insomnia diagnosis, greater total sleep time variability predicted poorer working memory and verbal learning performance. Further, following sleep treatment, a reduction in total wake time predicted improved working memory performance and a reduction in total sleep time variability predicted improved verbal learning performance. These findings raise the possibility that sleep disturbance may contribute to cognitive dysfunction in bipolar disorder and highlight the importance of treating sleep disturbance in bipolar disorder. Published by Elsevier Ltd.

  4. De Novo ACTA2 Mutation Causes a Novel Syndrome of Multisystemic Smooth Muscle Dysfunction

    Science.gov (United States)

    Milewicz, Dianna M.; Østergaard, John R.; Ala-Kokko, Leena M.; Khan, Nadia; Grange, Dorothy K.; Mendoza-Londono, Roberto; Bradley, Timothy J.; Olney, Ann Haskins; Adès, Lesley; Maher, Joseph F.; Guo, Dongchuan; Buja, L. Maximilian; Kim, Dong; Hyland, James C.; Regalado, Ellen S.

    2011-01-01

    Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of α-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut and pulmonary hypertension. PMID:20734336

  5. Neurological soft signs, cognitive dysfunction and ventricular brain ration in schizophrenics.

    Science.gov (United States)

    Lal, N; Tiwari, S C; Srivastava, S; Khalid, A; Siddhartha; Kohli, N

    1998-04-01

    An association between cognitive dysfunction, neurological soft signs, enlarged brain ventricles and widened cortical sulci has been reported in schizophrenia. The present work aimed to study the relevance of positive and negative dichotomy with relation to neuropsychological performance of the schizophrenic patients, and the presence of neurological soft signs. In 23 schizophrenics patients diagnosed according to DSM-III-R of which 14 were of positive subtype and 9 were of negative subtype. At least one neurological soft sign was present in all the patients. The positive group had higher WMS and IQ scores and lower BGT scores than the negative group. Negative, correlation was seen for WMS and BGT scores with Ventricular Brain Ratio (VBR), and the soft signs showed positive correlation in the positive subtype only.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lamproglou, I. [Laboratoire de Biophysique, Paris (France); Chen, Q.M.; Poisson, M. [Hopital de la Salpetriere, Paris (France)] [and others

    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 {le} 0.001) and two-way avoidance (18% vs. 40%, p {le} 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p {le} 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.

  7. Severe cognitive dysfunction and shrinking lung syndrome in systemic lupus erythematous

    Directory of Open Access Journals (Sweden)

    Breno José Alencar Pires Barbosa

    2014-12-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease that can affect any organ or system. Neuropsychiatric and pulmonary involvement can occur in 40 and 50% of patients respectively, and may occur in several different clinical forms. While the main neuropsychiatric manifestations are represented by cognitive impairment, organic cerebral syndromes, delirium, psychosis, seizures, and peripheral neuropathies, the main forms of pulmonary involvement are pleurisy with or without pleural effusion, pneumonitis, interstitial disease, pulmonary hypertension, and alveolar hemorrhage. The authors report the case of a 49-year-old woman whose first manifestation of SLE was represented by two rare manifestations: rapidly progressive cognitive impairment, which was associated with respiratory failure caused by the shrinking lung syndrome. The authors call attention to the under-diagnosis of lupus pulmonary complications and its association with severe cognitive impairment that often necessitates aggressive treatment.

  8. Cognitive and behaviour dysfunction of children with neurocysticercosis: a cross-sectional study.

    Science.gov (United States)

    Prasad, Rajniti; Shambhavi; Mishra, Om P; Upadhyay, Shashi K; Singh, Tej B; Singh, Utpal Kant

    2014-10-01

    Eighty-three confirmed cases of neurocysticercosis diagnosed as per modified delBrutto criteria were enrolled in the study (Group-I) to observe cognitive and behavioural changes. Controls consisted of two groups: children with idiopathic generalized tonic-clonic seizure (Group-II) and normal children with non-specific cough (Group-III). Cases and controls were subjected to cognitive and behaviour assessment. There was significant difference in the intelligence quotient (IQ) of cases in domains of visual perception, immediate recall, analysis synthesis and reasoning, verbal ability, memory and spatial ability. In the age group of 6-18 years, cases had significantly more behaviour problems than control without seizure, in domains of anxious depressed, withdrawn depressed, somatic problems, social problems and rule-breaking behaviour. Neurocysticercosis causes decline in cognitive function and behaviours in older children, which should be recognized early for appropriate management and to avoid undue parental anxiety.

  9. 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

    2017-01-01

    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 ha

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

    Science.gov (United States)

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

    2016-04-01

    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. 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. 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; PCMBs was predictive for larger volume of brain necrosis (PCMBs 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). CMBs is a common radiological manifestation in NPC patients with RN. The number of temporal CMBs is independently associated with increased likelihood of cognitive dysfunction in patients with RN. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Telmisartan attenuates cognitive impairment caused by chronic stress in rats.

    Science.gov (United States)

    Wincewicz, Dominik; Braszko, Jan J

    2014-06-01

    The potential effect of chronic treatment with telmisartan, an angiotensin type 1 receptor blocker (ARB) and partial agonist of peroxisome proliferator--activated receptor γ (PPARγ), on stress-related disorders is a matter of considerable interest. The existing data suggest that angiotensin II (Ang II) plays a major role in exaggerated sympathetic and hormonal response to stress. Enhanced formation of Ang II and increased AT1 receptor activity is associated with devastating impact of stress on central nervous system, which may trigger many psychiatric disorders such as depression, schizophrenia or post-traumatic stress disorder. Some of the anti-stress effects of ARBs have already been proven but these on the stress-induced cognitive impairment were examined only for candesartan. In this study, we tested a hypothesis that blockade of stress response by another ARB telmisartan alleviates the negative effect of prolonged restraint stress on cognitive functions of male Wistar rats. The preventive action of long-lasting treatment with telmisartan (1mg/kg body weight) against impairment caused by chronic stress (2h daily for 21 days) on recall was evaluated in a passive avoidance (PA) situation and object recognition test (ORT). Locomotor activity and anxiety behavior were tested respectively, in an open field and an elevated plus-maze. The results of this study indicate that telmisartan diminishes deleterious effects of chronic restraint stress on memory in a statistically significant manner (ptelmisartan may constitute a new therapeutic option in a stress-related cognitive impairment. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio [Niigata Univ. (Japan). Brain Research Inst.

    2001-12-01

    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)

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

    Institute of Scientific and Technical Information of China (English)

    Dao-Rui Yu; Tao Wang; Li-Ping Ji; Xing-Yue Fang; Xi-Nan Yi; Qi-Bing Liu

    2016-01-01

    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.

  14. 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

    to the dysfunction of pelvic organs after radiotherapy for anal cancer. METHOD: A questionnaire regarding anorectal, urinary and sexual symptoms was sent to anal cancer patients without recurrence or colostomy, diagnosed during 1996-2003, and treated with curative intent (chemo)radiotherapy at three Danish centres....... 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......%. Stress, urge or another type of urinary incontinence occurred at least monthly in 45% and caused great distress in 21%. Urinary urgency occurred at least monthly in 48% but only caused great distress in 14%. Sexual desire was severely decreased in 58% and only 24% were satisfied with their sexual...

  15. Suprascapular nerve injury: A cause to consider in shoulder pain and dysfunction.

    Science.gov (United States)

    Yao, Kaihan; Yew, Wei Ping

    2016-05-13

    Suprascapular nerve injury is increasingly being recognized as an important cause of shoulder dysfunction. The non-specific clinical features of suprascapular nerve injury can make diagnosis difficult. However, it is essential for clinicians to consider it as part of the differential diagnoses in patients with vague pain or sensory disturbances over the posterosuperior part of their shoulder or have unexplained atrophy and weakness of their supraspinatus or infraspinatus muscle. Electrodiagnostic studies are useful in confirming and localising the nerve injury, while MRIs can be employed to determine the cause of nerve injury and assess the integrity of the rotator cuff muscles. Isolated suprascapular nerve injury can be managed with a trial of conservative management for at least 6 months. Subsequently, decompression of the nerve through open or arthroscopic techniques can be considered - both are associated with high rates of pain relief and functional improvement.

  16. 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

  17. 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

  18. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  19. Relationship between Cognitive Performance and Motor Dysfunction in Patients with Parkinson’s Disease: A Pilot Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Valentina Varalta

    2015-01-01

    Full Text Available The aim of this pilot cross-sectional study was to extensively investigate the relationships between cognitive performance and motor dysfunction involving balance and gait ability in patients with Parkinson’s disease. Twenty subjects with Parkinson’s disease underwent a cognitive (outcomes: Frontal Assessment Battery-Italian version, Montreal overall Cognitive Assessment, Trail Making Test, Semantic Verbal Fluency Test, and Memory with Interference Test and motor (outcomes: Berg Balance Scale, 10-Meter Walking Test, 6-Minute Walking Test, Timed Up and Go Test performed also under dual task condition, and Unified Parkinson’s Disease Rating Scale assessment. Our correlation analyses showed that balance skills are significantly correlated with executive functions, cognitive impairment, and ability to switch attention between two tasks. Furthermore, functional mobility showed a significant correlation with cognitive impairment, verbal fluency, and ability to switch attention between two tasks. In addition, the functional mobility evaluated under the dual task condition showed a significant correlation with cognitive impairment and ability to switch attention between two tasks. These findings might help early identification of cognitive deficits or motor dysfunctions in patients with Parkinson’s disease who may benefit from rehabilitative strategies. Future prospective larger-scale studies are needed to strengthen our results.

  20. Frailty, cognitive impairment, and functional disability in older women with female pelvic floor dysfunction.

    Science.gov (United States)

    Erekson, Elisabeth A; Fried, Terri R; Martin, Deanna K; Rutherford, Thomas J; Strohbehn, Kris; Bynum, Julie P W

    2015-06-01

    There is a growing body of evidence demonstrating frailty as an important predictor of surgical outcomes in older adults undergoing major surgeries. The age-related onset of many symptoms of female pelvic floor dysfunction (PFD) in women suggests that many women seeking treatment for PFD may also have a high prevalence of frailty, which could potentially impact the risks and benefits of surgical treatment options. Our primary objective was to determine the prevalence of frailty, cognitive impairment, and functional disability in older women seeking treatment for PFD. We conducted a cross-sectional study with prospective recruitment between September 2011 and September 2012. Women, age 65 years and older, were recruited at the conclusion of their new patient consultation for PFD at a tertiary center. A comprehensive geriatric screening including frailty measurements (Fried Frailty Index), cognitive screening (Saint Louis University Mental Status score), and functional status evaluation for activities of daily living (Katz ADL score) was conducted. Sixteen percent (n/N = 25/150) of women were categorized as frail according to the Fried Frailty Index score. After adjusting for education level, 21.3 % of women (n/N = 32/150) screened positive for dementia and 46 (30.7 %) reported functional difficulty or dependence in performing at least one Katz ADL. Sixty-nine women (46.0 %) chose surgical options for treatment of their PFD at the conclusion of their new patient visit with their physician. Frailty, cognitive impairment, and functional disability are common in older women seeking treatment for PFD.

  1. Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.

    Directory of Open Access Journals (Sweden)

    Sung-Min Kim

    Full Text Available BACKGROUND: Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained can affect the loss of motor neurons or cognitive function in an in vivo model of ALS. OBJECTIVE: To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice. METHODS: Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation. RESULTS: Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation. CONCLUSIONS: Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in

  2. Hypothalamic dysfunction

    Science.gov (United States)

    ... common causes of hypothalamic dysfunction are surgery, traumatic brain injury, tumors, and radiation. Other causes include: Anorexia nervosa or bulimia Bleeding Genetic disorders that cause iron ...

  3. 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

  4. 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

  5. Lack of Dietary Polyunsaturated Fatty Acids Causes Synapse Dysfunction in the Drosophila Visual System.

    Science.gov (United States)

    Ziegler, Anna B; Ménagé, Cindy; Grégoire, Stéphane; Garcia, Thibault; Ferveur, Jean-François; Bretillon, Lionel; Grosjean, Yael

    2015-01-01

    Polyunsaturated fatty acids (PUFAs) are essential nutrients for animals and necessary for the normal functioning of the nervous system. A lack of PUFAs can result from the consumption of a deficient diet or genetic factors, which impact PUFA uptake and metabolism. Both can cause synaptic dysfunction, which is associated with numerous disorders. However, there is a knowledge gap linking these neuronal dysfunctions and their underlying molecular mechanisms. Because of its genetic manipulability and its easy, fast, and cheap breeding, Drosophila melanogaster has emerged as an excellent model organism for genetic screens, helping to identify the genetic bases of such events. As a first step towards the understanding of PUFA implications in Drosophila synaptic physiology we designed a breeding medium containing only very low amounts of PUFAs. We then used the fly's visual system, a well-established model for studying signal transmission and neurological disorders, to measure the effects of a PUFA deficiency on synaptic function. Using both visual performance and eye electrophysiology, we found that PUFA deficiency strongly affected synaptic transmission in the fly's visual system. These defects were rescued by diets containing omega-3 or omega-6 PUFAs alone or in combination. In summary, manipulating PUFA contents in the fly's diet was powerful to investigate the role of these nutrients on the fly´s visual synaptic function. This study aims at showing how the first visual synapse of Drosophila can serve as a simple model to study the effects of PUFAs on synapse function. A similar approach could be further used to screen for genetic factors underlying the molecular mechanisms of synaptic dysfunctions associated with altered PUFA levels.

  6. CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms

    Science.gov (United States)

    Damaj, Lena; Lupien-Meilleur, Alexis; Lortie, Anne; Riou, Émilie; Ospina, Luis H; Gagnon, Louise; Vanasse, Catherine; Rossignol, Elsa

    2015-01-01

    CACNA1A loss-of-function mutations classically present as episodic ataxia type 2 (EA2), with brief episodes of ataxia and nystagmus, or with progressive spinocerebellar ataxia (SCA6). A minority of patients carrying CACNA1A mutations develops epilepsy. Non-motor symptoms associated with these mutations are often overlooked. In this study, we report 16 affected individuals from four unrelated families presenting with a spectrum of cognitive impairment including intellectual deficiency, executive dysfunction, ADHD and/or autism, as well as childhood-onset epileptic encephalopathy with refractory absence epilepsy, febrile seizures, downbeat nystagmus and episodic ataxia. Sequencing revealed one CACNA1A gene deletion, two deleterious CACNA1A point mutations including one known stop-gain and one new frameshift variant and a new splice-site variant. This report illustrates the phenotypic heterogeneity of CACNA1A loss-of-function mutations and stresses the cognitive and epileptic manifestations caused by the loss of CaV2.1 channels function, presumably affecting cerebellar, cortical and limbic networks. PMID:25735478

  7. 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.

  8. Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training

    Science.gov (United States)

    Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira

    2016-01-01

    Background Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Methods Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Results Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Conclusions Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation. PMID:27880816

  9. Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

    Science.gov (United States)

    Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; Dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Antunes, Hanna Karen Moreira

    2016-01-01

    Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

  10. A new test battery to assess aphasic disturbances and associated cognitive dysfunctions -- German normative data on the aphasia check list.

    Science.gov (United States)

    Kalbe, Elke; Reinhold, Nadine; Brand, Matthias; Markowitsch, Hans J; Kessler, Josef

    2005-10-01

    Aphasia, defined as an acquired impairment of linguistic abilities, can be accompanied by a diversity of neuropsychological dysfunction. Accordingly, the necessity to include cognitive testing in the diagnosis of aphasia is increasingly recognized. Here we present the Aphasia Check List (ACL), a new test battery for the assessment of aphasic and associated cognitive disorders. The language part of the battery provides a differentiated profile of important linguistic abilities. In addition, the ACL includes nonverbal screening tests for three neuropsychological domains: memory, attention, and reasoning. Dysfunctions in these domains have been observed in aphasic patients and can have an impact on language function. The ACL is applicable to patients with language disturbances of different etiologies, different stages of disease, and to patients with mild to severe aphasia. As the entire test duration is only about 30 minutes, the ACL is also economically valuable. It thus presents an adequate starting point in aphasia diagnosis for a wide range of patients. Here we describe the construction of the ACL, and the normative study of its original German version with 154 aphasic patients and 106 healthy comparison subjects. The ACL cognition part revealed additional neuropsychological dysfunction in the aphasia group. We present the patterns of these dysfunctions and their correlations with language deficits.

  11. 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.

  12. Early Myocardial Dysfunction is Not Caused by Mitochondrial Abnormalities in a Rat Model of Peritonitis

    NARCIS (Netherlands)

    Smeding, Lonneke; van der Laarse, Willem J.; van Veelen, Toke A.; Lamberts, Regis R.; Niessen, Hans W. M.; Kneyber, Martin C. J.; Groeneveld, A. B. Johan; Plotz, Frans B.

    2012-01-01

    Background. Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation

  13. Emerging neuromodulatory molecules for the treatment of neurogenic erectile dysfunction caused by cavernous nerve injury

    Institute of Scientific and Technical Information of China (English)

    Anthony J. Bella; Guiting Lin; Ilias Cagiannos; Tom F. Lue

    2008-01-01

    Advances in the neurobiology of growth factors, neural development, and prevention of cell death have resulted in a heightened clinical interest for the development of protective and regenerative neuromodulatory strategies for the cavernous nerves (CNs), as therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function. Nitric oxide released from the axonal end plates of these nerves within the corpora cavernosa causes relaxation of smooth muscle, initiating the haemodynamic changes of penile erection as well as contributing to maintained tumescence; the loss of CN function is primarily responsible for the development of erectile dysfunction (ED) after pelvic surgery and serves as the primary target for potential neuroprotective or regenerative strategies. Evidence from pre-clinical studies for select neuromodulatory approaches is reviewed, including neurotrophins, glial cell line-derived neurotrophic factors (GDNF), bone morphogenic proteins, immunophilin ligands,erythropoetin (EPO), and stem cells.

  14. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

    Science.gov (United States)

    Nykjaer, A; Fyfe, J C; Kozyraki, R; Leheste, J R; Jacobsen, C; Nielsen, M S; Verroust, P J; Aminoff, M; de la Chapelle, A; Moestrup, S K; Ray, R; Gliemann, J; Willnow, T E; Christensen, E I

    2001-11-20

    Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D(3) complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D(3) in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid-carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D(3). This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.

  15. Brain dysfunction in anorexia nervosa: cause or consequence of under-nutrition?

    Science.gov (United States)

    Hay, Phillipa J; Sachdev, Perminder

    2011-05-01

    Imaging studies that demonstrate loss of brain substance help explain why people with anorexia nervosa have cognitive deficits and may help to elucidate the cognitive style found in many patients. It is not known whether a neurobiological vulnerability predisposes to anorexia nervosa or if this is associated with maintenance of symptoms once the illness develops. Evidence emerging from functional neuro-imaging studies raise the possibility of a biological abnormality that may predispose to anorexia nervosa. Studies have found abnormal functioning in the frontal, limbic, occipital, striatal and cerebellar regions that may persist after recovery. However, most recent cross-sectional and prospective studies indicate improved cerebral activity and mixed findings in regards to neurocognitve function with recovery from anorexia nervosa. The elucidation of the neurobiology of anorexia nervosa has benefited from recent advances in neuro-imaging and cognitive neuroscience. Further research is needed to examine the degree to which abnormalities are a consequence of starvation or are caused by a putative anorexia nervosa endophenotype.

  16. Causes of Multiple Organ Dysfunction During Cardiosurgical Operations under Extracorporeal Circulation

    Directory of Open Access Journals (Sweden)

    M. A. Babayev

    2010-01-01

    Full Text Available Objective: to reveal possible causes of postoperative multiple organ dysfunction syndrome (MODS in patients after surgery under extracorporeal circulation (EC, by measuring the level and balance of pro- and anti-inflammatory cytokines. Subjects and methods. The investigation enrolled 162 patients who had undergone operations on the heart and thoracic aorta. The levels of interleukins (IL-6, IL-8, and IL-10 were determined by ELISA. Results. At surgery under EC, MODS was encountered in 5.7%, mortality was 55.6%. The principal causes of MODS were prolonged EC concurrent with bleeding (23%, massive hemorrhage (16%, perioperative myocardial infarction and cardiogenic shock (15%, prolonged EC (12%, acute lung injury (12%, disseminated intravascular coagulation (10%, allergic and anaphylactic reactions (9%, and intravascular hemolysis (6%. The levels of pro- and anti-inflammatory cytokines were substantially increased in all the patients after surgery under EC irrespective of the presence of MODS in the postoperative period. The patients with MODS displayed pro- and anti-inflammatory cytokine imbalance due to a preponderance of the proinflammatory activity of a systemic response. During massive hemorrhage (more than 20 ml/kg, the patients with MODS exhibited a reduction in the two pools of cytokines. In the absence of MODS, there was a parallel increase in both pro- and anti-inflammatory cytokines. The magnitude of a change in the level of cytokines is related to the volume of blood loss. During prolonged EC (more than 170 min, the patients with MODS had a higher pro- and anti-inflammatory cytokine ratio due to the elevated levels of both pools, but the elevation of anti-inflammatory cytokines was more pronounced. In the patients without MODS, the values of both groups of interleukins were sigmficantly unchanged with longer duration of EC. Key words: multiple organ dysfunction syndrome, systemic inflammatory reaction, interleukins 6, 8, 10

  17. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Damon T. Jacobs

    2016-07-01

    Full Text Available Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139 encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  18. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome.

    Science.gov (United States)

    Jacobs, Damon T; Silva, Luciane M; Allard, Bailey A; Schonfeld, Michael P; Chatterjee, Anindita; Talbott, George C; Beier, David R; Tran, Pamela V

    2016-07-01

    Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139) encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc) was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp) expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  19. 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.

  20. 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 fibrino

  1. 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.

  2. Peripartum heart failure caused by left ventricular diastolic dysfunction: a case report.

    Science.gov (United States)

    Kakogawa, Jun; Nako, Takafumi; Igarashi, Suguru; Nakamura, Shin; Tanaka, Mamoru

    2014-08-01

    Peripartum cardiomyopathy is a rare but potentially life-threatening condition. The current definition of peripartum cardiomyopathy only includes patients with systolic dysfunction. We describe a 25-year-old nulligravid patient with heart failure, i.e. left ventricular diastolic dysfunction with preserved systolic dysfunction during the third trimester of pregnancy. She complained of dyspnea and was referred to our hospital at 31 weeks of gestation. The patient met the clinical criteria for peripartum cardiomyopathy with the exception of systolic dysfunction. Brain-type natriuretic peptide levels peaked at 1447 pg/dL. The patient responded to therapy for heart failure and showed resolution of her diastolic dysfunction by 1 month postpartum. The case demonstrated the important role of diastolic dysfunction in peripartum heart failure and the possibility of clarifying the pathophysiology of peripartum cardiomyopathy by evaluating diastolic function. Further investigations are needed to provide evidence regarding the clinical role of diastolic dysfunction in peripartum heart failure.

  3. Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction.

    Science.gov (United States)

    Pitcher, Jonathan; Abt, Anna; Myers, Jaclyn; Han, Rachel; Snyder, Melissa; Graziano, Alessandro; Festa, Lindsay; Kutzler, Michele; Garcia, Fernando; Gao, Wen-Jun; Fischer-Smith, Tracy; Rappaport, Jay; Meucci, Olimpia

    2014-02-01

    Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that μ-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS.

  4. 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.

  5. Mindfulness-based stress reduction for older adults with worry symptoms and co-occurring cognitive dysfunction.

    Science.gov (United States)

    Lenze, Eric J; Hickman, Steven; Hershey, Tamara; Wendleton, Leah; Ly, Khanh; Dixon, David; Doré, Peter; Wetherell, Julie Loebach

    2014-10-01

    Mindfulness-based stress reduction (MBSR) has the potential to reduce worry and improve cognitive functioning. In this treatment development project, we examined MBSR in older adults with worry symptoms and co-occurring cognitive dysfunction. We examined (i) acceptability of MBSR, (ii) whether MBSR needs to be lengthened providing more repetition, (iii) MBSR's benefits for worry reduction and cognitive improvements, and (iv) continued use of MBSR techniques during follow-up. Two sites (St. Louis and San Diego) enrolled individuals aged 65 years or older with significant anxiety-related distress plus subjective cognitive dysfunction, into traditional 8-session MBSR groups and 12-session groups that had the same content but more repetition of topics and techniques. We examined measures of mindfulness, worry, and a neuropsychological battery focused on memory and executive function before and after the MBSR program, and we followed up participants for 6 months after the completion of MBSR regarding their continued use of its techniques. Participants (N = 34) showed improvements in worry severity, increases in mindfulness, and improvements in memory as measured by paragraph learning and recall after a delay, all with a large effect size. Most participants continued to use MBSR techniques for 6 months post-instruction and found them helpful in stressful situations. There was no evidence that the extended 12-week MBSR produced superior cognitive or clinical outcomes, greater satisfaction, or greater continuation of MBSR techniques than 8-week MBSR. These preliminary findings are promising for the further testing and use of MBSR in older adults suffering from clinical worry symptoms and co-occurring cognitive dysfunction. These are common problems in a broad range of older adults, many of whom have anxiety and mood disorders; therefore, stress reduction intervention for them may have great public health value. Copyright © 2014 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Han, Bing; Wang, Jin-Hua; Geng, Yuan; Shen, Li; Wang, Hua-Long; Wang, Yan-Yong; Wang, Ming-Wei

    2017-01-01

    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. 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. 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. 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. © 2017 The Author(s)Published by S. Karger AG, Basel.

  8. Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction.

    Science.gov (United States)

    Wolf, Matthew B; Baynes, John W

    2007-02-01

    We investigated the ability of cadmium and mercury ions to cause endothelial dysfunction in bovine pulmonary artery endothelial cell monolayers. Exposure of monolayers for 48 h to metal concentrations greater than 3-5 microM produced profound cytotoxicity (increased lactate dehydrogenase leakage), a permeability barrier failure, depletion of glutathione and ATP and almost complete inhibition of the activity of key thiol enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In contrast, metal concentrations less than 1-2 microM induced increases in glutathione and thiol-enzyme activities with minimal changes in LDH leakage, barrier function and ATP content. At shorter incubation times (24 h or less), high concentrations of cadmium caused glutathione induction rather than depletion. Thus, oxidative stress and cytotoxicity induced by lower concentrations of the metal ions stimulate compensatory responses, including increased synthesis of glutathione, which presumably preserved the activity of key thiol enzymes, however these responses were not sustainable at higher metal ion concentrations. We conclude, while high concentrations of heavy metals are cytotoxic, lower concentration induce a compensatory protective response, which may explain threshold effects in metal-ion toxicity.

  9. Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans.

    Science.gov (United States)

    Kuwahara, Tomoki; Koyama, Akihiko; Gengyo-Ando, Keiko; Masuda, Mayumi; Kowa, Hisatomo; Tsunoda, Makoto; Mitani, Shohei; Iwatsubo, Takeshi

    2006-01-06

    Mutations in alpha-synuclein gene cause familial form of Parkinson disease, and deposition of wild-type alpha-synuclein as Lewy bodies occurs as a hallmark lesion of sporadic Parkinson disease and dementia with Lewy bodies, implicating alpha-synuclein in the pathogenesis of Parkinson disease and related neurodegenerative diseases. Dopamine neurons in substantia nigra are the major site of neurodegeneration associated with alpha-synuclein deposition in Parkinson disease. Here we establish transgenic Caenorhabditis elegans (TG worms) that overexpresses wild-type or familial Parkinson mutant human alpha-synuclein in dopamine neurons. The TG worms exhibit accumulation of alpha-synuclein in the cell bodies and neurites of dopamine neurons, and EGFP labeling of dendrites is often diminished in TG worms expressing familial Parkinson disease-linked A30P or A53T mutant alpha-synuclein, without overt loss of neuronal cell bodies. Notably, TG worms expressing A30P or A53T mutant alpha-synuclein show failure in modulation of locomotory rate in response to food, which has been attributed to the function of dopamine neurons. This behavioral abnormality was accompanied by a reduction in neuronal dopamine content and was treatable by administration of dopamine. These phenotypes were not seen upon expression of beta-synuclein. The present TG worms exhibit dopamine neuron-specific dysfunction caused by accumulation of alpha-synuclein, which would be relevant to the genetic and compound screenings aiming at the elucidation of pathological cascade and therapeutic strategies for Parkinson disease.

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

    Science.gov (United States)

    Kanouchi, Hiroaki; Kakimoto, Toshiaki; Nakano, Hideya; Suzuki, Masahiro; Nakai, Yuji; Shiozaki, Kazuhiro; Akikoka, Kohei; Otomaru, Konosuke; Nagano, Masanobu; Matsumoto, Mitsuharu

    2016-01-01

    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.

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

    Science.gov (United States)

    Kanouchi, Hiroaki; Kakimoto, Toshiaki; Nakano, Hideya; Suzuki, Masahiro; Nakai, Yuji; Shiozaki, Kazuhiro; Akikoka, Kohei; Otomaru, Konosuke; Nagano, Masanobu; Matsumoto, Mitsuharu

    2016-01-01

    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. PMID:26943920

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

    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...

  14. [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.

  15. Recent Clinical History and Cognitive Dysfunction for Attention and Executive Function among Human Immunodeficiency Virus-Infected Patients

    Science.gov (United States)

    Tate, David F.; DeLong, Allison; McCaffrey, Daniel E.; Kertesz, Kinga; Paul, Robert H.; Conley, Jared; Russell, Troy; Coop, Kathleen; Gillani, Fizza; Flanigan, Timothy; Tashima, Karen; Hogan, Joseph W.

    2011-01-01

    This study examined the association between recent trends in CD4 and viral loads and cognitive test performance with the expectation that recent history could predict cognitive performance. Eighty-three human immunodeficiency virus (HIV)-infected patients with a mean CD4 count of 428 copies/ml were examined in this study (62% with undetectable plasma viral load [PVL]). We investigated the relationships between nadir CD4 cell count, 1-year trends in immunologic function/PVLs, and cognitive performance across several domains using linear regression models. Nadir CD4 cell count was predictive of current executive function (p = .004). One year clinical history for CD4 cell counts and/or PVLs were predictive of executive function, attention/working memory, and learning/memory measures (p < .05). Models that combined recent clinical history trends and nadir CD4 cell counts suggested that recent clinical trends were more important in predicting current cognitive performance for all domains except executive function. This research suggests that recent CD4 and viral load history is an important predictor of current cognitive function across several cognitive domains. If validated, clinical variables and cognitive dysfunction models may improve our understanding of the dynamic relationships between disease evolution and progression and CNS involvement. PMID:21873325

  16. Dogs with Cognitive Dysfunction as a Spontaneous Model for Early Alzheimer's Disease: A Translational Study of Neuropathological and Inflammatory Markers.

    Science.gov (United States)

    Schütt, Trine; Helboe, Lone; Pedersen, Lars Østergaard; Waldemar, Gunhild; Berendt, Mette; Pedersen, Jan Torleif

    2016-03-15

    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 of the diffuse subtype as no dense-core or neuritic plaques were found. The Aβ deposition followed a progressive pattern in four maturation stages. Accumulation of the Aβ peptide was also observed in the vessel walls. Both immunohistochemically and biochemically measured levels of Aβ pathology in prefrontal cortex showed a consistent positive correlation to age but not to cognitive deficit severity. No evidence of neurofibrillary tau pathology was found. The level of pro-inflammatory cytokines was generally low and showed no significant association to cognitive status. The findings of the present study support the senescent dog with spontaneous cognitive dysfunction as a valuable non-transgenic model for further investigations of the molecular events involved in the neurodegenerative processes associated with aging and early stage AD, especially the Aβ-related pathology.

  17. 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

  18. Systemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthood

    Science.gov (United States)

    Lomeli, Naomi; Bota, Daniela A.

    2017-01-01

    Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15–50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age. PMID:27851909

  19. Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

    NARCIS (Netherlands)

    Hoeks, J.; Herpen, N.A.; Mensink, M.R.; Moonen-Kornips, E.; Beurden, van D.; Hesselink, M.K.C.; Schrauwen, P.

    2010-01-01

    OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we

  20. Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

    NARCIS (Netherlands)

    Hoeks, J.; Herpen, N.A.; Mensink, M.R.; Moonen-Kornips, E.; Beurden, van D.; Hesselink, M.K.C.; Schrauwen, P.

    2010-01-01

    OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we em

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Targeted overexpression of mitochondrial catalase prevents radiation-induced cognitive dysfunction.

    Science.gov (United States)

    Parihar, Vipan K; Allen, Barrett D; Tran, Katherine K; Chmielewski, Nicole N; Craver, Brianna M; Martirosian, Vahan; Morganti, Josh M; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M; Nelson, Gregory A; Allen, Antiño R; Limoli, Charles L

    2015-01-01

    Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2. Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology. Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain.

  3. Synergism of ochratoxin B and calcium-channel antagonist verapamil caused mitochondrial dysfunction.

    Science.gov (United States)

    Chatopadhyay, Pronobesh; Tariang, Banlumlang; Agnihotri, Amit; Veer, Vijay

    2014-09-01

    We examined the mechanism by which the ochratoxin B induced interaction with calcium-channel antagonist verapamil and mitochondrial dysfunction of the rat trachea in vitro experiment. The tracheas were cut into 2-3 mm wide rings and suspended in a tissue bath. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Verapamil (1 × 10(-6) M) produced a concentration-dependent contraction response in rat's tracheal rings pre-contracted by acetylcholine. Incubation of rat's tracheal rings with the ochratoxin B significantly potentiated the contraction responses of verapamil. Verapamil and OTB accelerate the overloading of Ca(2+) in tracheal smooth muscle contributes the tissue toxicity as shown in electron microscopy and mitochondrial enzymes, through a mechanism that could involve perturbations of Ca(2+) homeostasis. These results proved that ochratoxin B is a potential vasoconstrictor mycotoxin with the presence of calcium-channel antagonist. In conclusion, disturbance of Ca(2+) homeostasis caused by OTA and plays a significant role in produces toxicity through mitochondrial enzyme inhibition.

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

    Directory of Open Access Journals (Sweden)

    Jin Hyo Kim

    Full Text Available 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.

  5. 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.

  6. 吸烟与老年人认知功能障碍%Smoking and cognitive dysfunction in elder people

    Institute of Scientific and Technical Information of China (English)

    邓娟; 周华东; 李敬城; 王延江; 张猛; 高长越

    2005-01-01

    背景 : 随着老龄化社会的到来,认知功能障碍发病率的逐渐上升,人们开始关注吸烟对认知功能障碍的影响. 目的 :探讨吸烟对老年人认知功能障碍的影响,寻求进行干预的可能性. 设计:随机整群抽样调查. 单位:一所大学医院的神经内科. 对象:以抽签的方法从重庆市高新区、渝北区、渝中区中分别抽取了两个居委会≥ 60岁老年人共 3 012人,男 1 668人,女 1 344人. 方法:用简易智能量表( MMSE) 进行认知功能测定,采用 t检验和 Logistic回归多因素分析方法对测定结果进行分析. 主要观察指标:①吸烟的人口学分布.②老年人认知功能障碍的单因素和多因素分析结果. 结果:对 3 012人完成了 MMSE测定,总吸烟率为 35%,重庆市老年人认知功能异常率为 11.95%;吸烟人群中,现在吸烟者引起认知功能障碍为 11.8%,过去吸烟者为 4.5%,不吸烟者引起认知功能障碍为 5.3%. 结论:吸烟与认知功能障碍密切相关 (χ 2=6.59, P=0.047),文化程度、年龄、职业和性别均是老年人认知功能障碍的影响因素.吸烟人群中现在吸烟者对认知功能障碍的危险性较大 (RR=2.33, 95% CI= 1.37~ 5.82).吸烟是老年人认知功能减退的重要危险因素,老年人戒烟可能是降低认知功能障碍发生的有效策略.%BACKGROUND:With the trend of population aging,the morbidity of cognitive dysfunction has been gradually increased.People start to pay attention to the impact of smoking to cognitive dysfunction. OBJECTIVE:To investigate the effects of smoking on cognitive dysfunction in elder people,and explore the possibility of intervention. DESIGN:Randomized cluster sampling. SETTING:Neurology Department of a hospital. PARTICIPANTS:A total of 3 012 old people aged above 60 year were selected from two resident committees by drawing from Gaoxin district,Yubei district and Yuzhong district of Chongqing in which there were 1 668 males and 1 344 females

  7. Pre- and postnatal exposure to kynurenine causes cognitive deficits in adulthood.

    Science.gov (United States)

    Pocivavsek, Ana; Wu, Hui-Qiu; Elmer, Greg I; Bruno, John P; Schwarcz, Robert

    2012-05-01

    Levels of kynurenic acid (KYNA), an endogenous product of tryptophan degradation, are elevated in the brain and cerebrospinal fluid of individuals with schizophrenia (SZ). This increase has been implicated in the cognitive dysfunctions seen in the disease, as KYNA is an antagonist of the α7 nicotinic acetylcholine receptor and the N-methyl-d-aspartate receptor, both of which are critically involved in cognitive processes and in a defining neurodevelopmental period in the pathophysiology of SZ. We tested the hypothesis that early developmental increases in brain KYNA synthesis might cause biochemical and functional impairments in adulthood. To this end, we stimulated KYNA formation by adding the KYNA precursor kynurenine (100 mg/day) to the chow fed to rat dams from gestational day 15 to postnatal day 21 (PD 21). This treatment raised brain KYNA levels in the offspring by 341% on PD 2 and 210% on PD 21. Rats were then fed normal chow until adulthood (PD 56-80). In the adult animals, basal levels of extracellular KYNA, measured in the hippocampus by in vivo microdialysis, were elevated (+12%), whereas extracellular glutamate levels were significantly reduced (-13%). In separate adult animals, early kynurenine treatment was shown to impair performance in two behavioral tasks linked to hippocampal function, the passive avoidance test and the Morris water maze test. Collectively, these studies introduce a novel, naturalistic rat model of SZ, and also suggest that increases in brain KYNA during a vulnerable period in brain development may play a significant role in the pathophysiology of the disease.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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......, 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....

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

    NARCIS (Netherlands)

    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.

    2016-01-01

    Background & Aims: 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

  11. Use of osteopathic manipulative treatment to manage compensated trendelenburg gait caused by sacroiliac somatic dysfunction.

    Science.gov (United States)

    Gilliss, Adam C; Swanson, Randel L; Janora, Deanna; Venkataraman, Venkat

    2010-02-01

    Gait dysfunctions are commonly encountered in the primary care setting. Compensated Trendelenburg gait is a gait dysfunction that was originally described in patients with weakness of ipsilateral hip abduction. This condition is thought to result from neuronal injury or myopathy. No treatment modalities currently exist for compensated Trendelenburg gait. The authors present a case in which osteopathic manipulative treatment may have improved a Trendelenburg gait dysfunction in a man aged 65 years with multiple sclerosis. Evidence of this improvement was obtained with the GaitMat II system for measuring numerous gait parameters. Based on the results reported in the present case, the authors propose that compensated Trendelenburg gait may arise from somatic dysfunction and may be corrected by osteopathic manipulative treatment.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Diet Induced Obesity in Sprague Dawley Rats Causes Microvascular and Neural Dysfunction

    Science.gov (United States)

    Davidson, Eric P.; Coppey, Lawrence J.; Calcutt, Nigel A.; Oltman, Christine L.; Yorek, Mark A.

    2010-01-01

    Background The objective was to determine the effect of diet induced obesity (DIO) on microvascular and neural function. Methods Rats were fed a standard or high fat diet for up to 32 weeks. Measurements were performed of vasodilation in epineurial arterioles by videomicroscopy, endoneurial blood flow by hydrogen clearance, nerve conduction velocity by electrical stimulation, size-frequency distribution of myelinated fibers of the sciatic nerve, intraepidermal nerve fiber density using confocal microscopy and thermal nociception using the Hargreaves method. Results Rats fed a high fat diet for 32 weeks developed sensory neuropathy as indicated by slowing of sensory nerve conduction velocity and thermal hypoalgesia. Motor nerve conduction velocity and endoneurial blood flow were not impaired. Mean axonal diameter of myelinated fibers of the sciatic nerve was unchanged in high fat fed rats compared to control. Intraepidermal nerve fiber density was significantly reduced in high fat fed rats. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased and expression of neutral endopeptidase (NEP) increased in epineurial arterioles of rats fed a high fat diet. In contrast, insulin-mediated vascular relaxation was increased in epineurial arterioles. NEP activity was significantly increased in the skin of the hindpaw. Markers of oxidative stress were increased in the aorta and serum of high fat fed rats but not in epineurial arterioles. Conclusion Chronic obesity causes microvascular and neural dysfunction. This is associated with increased expression of NEP but not oxidative stress in epineurial arterioles. NEP degrades vasoactive peptides which may explain the decrease in microvascular function. PMID:20503263

  16. 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

    2013-06-05

    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.

  17. Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice.

    Science.gov (United States)

    Nogami, Tatsuya; Beppu, Hideyuki; Tokoro, Takashi; Moriguchi, Shigeki; Shioda, Norifumi; Fukunaga, Kohji; Ohtsuka, Toshihisa; Ishii, Yoko; Sasahara, Masakiyo; Shimada, Yutaka; Nishijo, Hisao; Li, En; Kitajima, Isao

    2011-06-01

    Mutations of the ATRX gene, which encodes an ATP-dependent chromatin-remodeling factor, were identified in patients with α-thalassemia X-linked mental retardation (ATR-X) syndrome. There is a milder variant of ATR-X syndrome caused by mutations in the Exon 2 of the gene. To examine the impact of the Exon 2 mutation on neuronal development, we generated ATRX mutant (ATRX(ΔE2)) mice. Truncated ATRX protein was produced from the ATRX(ΔE2) mutant allele with reduced expression level. The ATRX(ΔE2) mice survived and reproduced normally. There was no significant difference in Morris water maze test between wild-type and ATRX(ΔE2) mice. In a contextual fear conditioning test, however, total freezing time was decreased in ATRX(ΔE2) mice compared to wild-type mice, suggesting that ATRX(ΔE2) mice have impaired contextual fear memory. ATRX(ΔE2) mice showed significantly reduced long-term potentiation in the hippocampal CA1 region evoked by high-frequency stimulation. Moreover, autophosphorylation of calcium-calmodulin-dependent kinase II (αCaMKII) and phosphorylation of glutamate receptor, ionotropic, AMPA 1 (GluR1) were decreased in the hippocampi of the ATRX(ΔE2) mice compared to wild-type mice. These findings suggest that ATRX(ΔE2) mice may have fear-associated learning impairment with the dysfunction of αCaMKII and GluR1. The ATRX(ΔE2) mice would be useful tools to investigate the role of the chromatin-remodeling factor in the pathogenesis of abnormal behaviors and learning impairment.

  18. 糖尿病性认知功能障碍研究进展%Progress on diabetic cognitive dysfunction

    Institute of Scientific and Technical Information of China (English)

    王萌; 纪汶君; 陈莉娜

    2015-01-01

    糖尿病性认知功能障碍是糖尿病的重要并发症之一。胰岛素通过MAPK和PI3-K/Akt信号通路对认知功能具有重要保护作用。胰岛素抵抗可导致tau蛋白的过度磷酸化,形成神经纤维节;可竞争性抑制胰岛素降解酶,减少β淀粉样蛋白的降解;增强氧化应激,破坏神经元结构和功能的完整性,从而损伤认知功能。%Diabetic cognitive dysfunction is one of the important complications of diabetes mellitus .Insulin plays an important protective role in cognitive function through MAPK and PI 3-K/Akt signaling pathway .Insulin resistance may give rise to excessive tau protein phosphorylation , formation of neurofibrillary tangles inhibits insulin degrading enzyme , reduces the degradation of amyloid β;enhances oxidative stress , further damages the integrity of the neu-ronal structure and function and eventually leads to cognitive dysfunction .

  19. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker.

    Science.gov (United States)

    Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

    2016-07-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.

  20. [Incidence and risk factors of postoperative cognitive dysfunction in patients underwent coronary artery bypass grafting surgery].

    Science.gov (United States)

    Ge, Yali; Ma, Zhengliang; Shi, Hongwei; Zhao, Yamei; Gu, Xiaoping; Wei, Haiyan

    2014-10-01

    To investigate the incidence rate and the risk factors for postoperative cognitive dysfunction (POCD) in patients underwent coronary artery bypass grafting surgery. A total of 147 patients underwent elective coronary artery bypass grafting (CABG) surgery between January to July 2013 were included in this study. POCD was diagnosed using a neuropsychological test battery. All enrolled patients were interviewed on the day before surgery, the seventh day and 3 months after surgery, respectively, by the same researcher, and were divided into two groups based on the results: the POCD group and the non-POCD group. The information, including age, sex, body mass index, educational status, comorbidities, history of smoking and drinking, ASA grade, left ventricular ejection fraction, operation method, duration of operations, regional cerebral oxygen saturation, the lowest haemoglobin concentrations and the haemoglobin concentration decline rate during the operation, tracheal catheter retention time, postoperative pain on visual analogue scales (VAS) and systemic inflammatory response syndrome score (SIRS score), were recorded based on a schedule of survey. Multivariate logistic regression was used to analyze the risk factors for POCD. A total of 101 patients finished this study. On 7 days and 3 months after surgery, 38 and 21 cases showed POCD, with an incidence rate at 37.6% and 20.8%, respectively. Interestingly, there was no significant difference in incidence of POCD between CABG and OPCABG group on both 7 days and 3 months after surgery (P>0.05). The logistic stepwise regression analysis indicated that the risk factors for POCD included advanced age (OR=1.177, 95%CI 1.071-1.292, P=0.001), the haemoglobin concentration decline rate (OR=1.334, 95%CI 1.152-1.545, PSIRS score (OR=2.815, 95%CI 1.014-7.818, P=0.047). The incidence rate of POCD was 37.6% and 20.8% on 7 days and 3 months after surgery respectively. Advanced age, the haemoglobin concentration decline rate and

  1. Impact of general versus epidural anesthesia on early post-operative cognitive dysfunction following hip and knee surgery

    Directory of Open Access Journals (Sweden)

    Mandal Sripurna

    2011-01-01

    Full Text Available Background : Post-operative cognitive dysfunction is the subtle cerebral complication temporally seen following surgery. The aim of this study was to compare the influence of either general anesthesia (GA or epidural anesthesia (EA on the early post-operative neurocognitive outcome in elderly (>59 years subjects undergoing hip and knee surgery. Methods : A total of 60 patients were recruited in a prospective, randomized, parallel-group study, comparable by age and sex. They were enrolled and randomized to receive either EA (n = 30 or GA (n = 30. All of them were screened using the Mini Mental State Examination (MMSE, with components of the Kolkata Cognitive Screening Battery. The operated patients were re-evaluated 1 week after surgery using the same scale. The data collected were analyzed to assess statistical significance. Results : We observed no statistical difference in cognitive behavior in either group pre-operatively, which were comparable with respect to age, sex and type of surgery. Grossly, a significant difference was seen between the two groups with respect to the perioperative changes in verbal fluency for categories and MMSE scores. However, these differences were not significant after the application of the Bonferroni correction for multiple analyses, except the significant differences observed only in the MMSE scores. Conclusions : We observed a difference in cognitive outcome with GA compared with EA. Certain aspects of the cognition were affected to a greater extent in this group of patients undergoing hip and knee surgery.

  2. Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level.

    Science.gov (United States)

    Kasbe, Prajapati; Jangra, Ashok; Lahkar, Mangala

    2015-01-01

    Mangiferin is a phytochemical primarily present in the stem, leaves and bark of Mangifera indica. It offers neuroprotection mainly through inhibition of oxidative stress, and decreasing proinflammatory cytokines level in the brain. Aluminium has been reported to cause oxidative stress-associated damage in the brain. In the present investigation, protective effect of mangiferin against aluminium chloride (AlCl3)-induced neurotoxicity and cognitive impairment was studied in male Swiss albino mice. AlCl3 (100 mg/kg) was administered once daily through oral gavage for 42 days. Mangiferin (20 and 40 mg/kg, p.o.) was given to mice for last 21 days of the study. We found cognitive dysfunction in AlCl3-treated group, which was assessed by Morris water maze test, and novel object recognition test. AlCl3-treated group showed elevated level of oxidative stress markers, proinflammatory cytokines level and lowered hippocampal brain-derived neurotrophic factor (BDNF) content. Mangiferin (40 mg/kg) prevented the cognitive deficits, hippocampal BDNF depletion, and biochemical anomalies induced by AlCl3-treatment. In conclusion, our data demonstrated that mangiferin offers neuroprotection in AlCl3-induced neurotoxicity and it may be a potential therapeutic approach in the treatment of oxido-nitrosative stress and inflammation-associated neurotoxicity. Copyright © 2015 Elsevier GmbH. All rights reserved.

  3. Cognitive impairment in childhood onset epilepsy: up-to-date information about its causes.

    Science.gov (United States)

    Kim, Eun-Hee; Ko, Tae-Sung

    2016-04-01

    Cognitive impairment associated with childhood-onset epilepsy is an important consequence in the developing brain owing to its negative effects on neurodevelopmental and social outcomes. While the cause of cognitive impairment in epilepsy appears to be multifactorial, epilepsy-related factors such as type of epilepsy and underlying etiology, age at onset, frequency of seizures, duration of epilepsy, and its treatment are considered important. In recent studies, antecedent cognitive impairment before the first recognized seizure and microstructural and functional alteration of the brain at onset of epilepsy suggest the presence of a common neurobiological mechanism between epilepsy and cognitive comorbidity. However, the overall impact of cognitive comorbidity in children with epilepsy and the independent contribution of each of these factors to cognitive impairment have not been clearly delineated. This review article focuses on the significant contributors to cognitive impairment in children with epilepsy.

  4. 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

  5. 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

    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. 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. 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. 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. Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy.

  6. Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy.

    Directory of Open Access Journals (Sweden)

    Patricia A Reis

    Full Text Available Neurological impairments are frequently detected in children surviving cerebral malaria (CM, the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW mice with Plasmodium berghei ANKA (PbA or a lethal strain of Plasmodium yoelii XL (PyXL, respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders.

  7. Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice

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    Anil Kumar

    2011-01-01

    l (D-galactose. Centella asiatica also attenuated enhanced acetylcholine esterase enzyme level in D-galactose senescence mice. Present study highlights the protective effect of Centella asiatica against D-galactose induced behavioral, biochemical and mitochondrial dysfunction in mice.

  8. 老年消化道肿瘤患者术后认知功能障碍12例临床分析%Clinical Analysis of Postoperative Cognitive Dysfunction in 12 Elderly Patients with Gastrointestinal Cancer

    Institute of Scientific and Technical Information of China (English)

    杨峥; 刘强; 周跃宁

    2011-01-01

    [Objective]To explore the cause, prevention and treatment of postoperative cognitive dysfunction in elderly patients with gastrointestinal cancer.[Methods]The clinical data of 136 elderly patients(aged over 65 years old) with gastrointestinal cancer after operation were analyzed retrospectively.[Results]Of 136 cases, 12 patients (8.8%) had postoperative cognitive dysfunction and were cured after treatment.[Conclusion]The cause of postoperative cognitive dysfunction in elderly cancer patients is multifactorial.Pertinent prevention and treatment before and after operation can obtain a good prognosis.%[目的]探讨老年消化道肿瘤患者术后认知功能障碍发生的原因和防治经验.[方法]回顾性分析136例65岁以上的消化道肿瘤患者术后的临床资料.[结果]136例患者出现术后认知功能障碍12例,占8.8%,经治疗后均痊愈.[结论]老年肿瘤患者术后精神障碍发生的原因是多方面的,通过手术前后有针对性的预防和治疗,一般预后良好.

  9. 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.

  10. Regional Coherence Alterations Revealed by Resting-State fMRI in Post-Stroke Patients with Cognitive Dysfunction.

    Directory of Open Access Journals (Sweden)

    Cheng-Yu Peng

    Full Text Available Post-stroke cognitive dysfunction greatly influences patients' quality of life after stroke. However, its neurophysiological basis remains unknown. This study utilized resting-state functional magnetic resonance imaging (fMRI to investigate the alterations in regional coherence in patients after subcortical stroke.Resting-state fMRI measurements were acquired from 16 post-stroke patients with poor cognitive function (PSPC, 16 post-stroke patients with good cognitive function (PSGC and 30 well-matched healthy controls (HC. Regional homogeneity (ReHo was used to detect alterations in regional coherence. Abnormalities in regional coherence correlated with scores on neuropsychological scales.Compared to the HC and the PSGC, the PSPC showed remarkably decreased ReHo in the bilateral anterior cingulate cortex and the left posterior cingulate cortex/precuneus. ReHo in the bilateral anterior cingulate cortex positively correlated with the scores on the Symbol Digit Modalities Test (r = 0.399, P = 0.036 and the Complex Figure Test-delayed recall subtest (r = 0.397, P = 0.036 in all post-stroke patients. Moreover, ReHo in the left posterior cingulate cortex/precuneus positively correlated with the scores on the Forward Digit Span Test (r = 0.485, P = 0.009 in all post-stroke patients.Aberrant regional coherence was observed in the anterior and posterior cingulate cortices in post-stroke patients with cognitive dysfunction. ReHo could represent a promising indicator of neurobiological deficiencies in post-stroke patients.

  11. Response activity of alveolar macrophages in pulmonary dysfunction caused by Leptospira infection

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    M. Marinho

    2008-01-01

    Full Text Available Leptopspirosis is a syndrome with different clinical manifestations including the most severe and often fatal forms of pulmonary disease of unknown etiology. Pulmonary injury during the inflammatory process has been associated with the excessive number of alveolar macrophages (AMs and polymorphonuclear leukocytes stimulated in the lungs and with the production of reactive oxygen and nitrogen intermediates and other inflammatory mediators. The aim of the present work was to evaluate the cellular immune response of AMs or inflammatory cells of hamsters during leptospirosis. The activity of AMs was determined by measuring nitric oxide (NO and protein production as well as inflammatory cell infiltration in bronchoalveolar lavage (BAL fluid. Pulmonary activity during infection was monitored by measuring pH, pressure of oxygen (PaO2, and pressure of carbon dioxide (PaCO2 in blood samples. Cellular immune response and its role in the genesis of leptospirosis have been incriminated as the main causes of tissue and pulmonary injuries, which consequently lead to the pulmonary dysfunction in severe cases of leptospirosis. The present results show a low production of NO in both supernatant of alveolar macrophage culture and BAL. In the latter, protein production was high and constant, especially during acute infection. Total and differential cell count values were 2.5X10(6 on day 4; 7.3X10(6 on day 21; and 2.3X10(6 on day 28 after infection, with lymphocytes (84.04% predominating over neutrophils (11.88% and monocytes (4.07%. Arterial blood gas analysis showed pulmonary compromising along with the infectious process, as observed in parameter values (mean±SD evidenced in the infected versus control group: PaO2 (60.47mmHg±8.7 vs. 90.09mmHg±9.18, PaCO2 (57.01mmHg±7.87 vs. 47.39mmHg±4.5 and pH (7.39±0.03 vs. 6.8±1.3. Results indicated that Leptospira infection in hamsters is a good experimental model to study leptospirosis. However, some of the immune

  12. 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

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    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.

  13. Research Advance in the Pathogenesis Study of Postoperative Cognitive Dysfunction%POCD发病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    张雄军; 王德明

    2012-01-01

    POCD is characterized by a persistent decline in cognitive function following anesthesia and surgery, identified by preoperative and postoperative cognitive testing. This testing requires a sensitive and comprehensive neuropsy-chological test battery assessing a variety of cognitive domains. However, the investigation and diagnosis of POCD is hampered by the absence of a consensus regarding the tests to be used as well as the operational definition of POCD. Consequently, the comparison between studies investi-gating POCD is diffkult.Therefore, further elaboration of POCD factors and pathogenesis, will help establish standards for POCD detection, diagnosis and control methods.%术后认知功能障碍(Postoperative Cognitive Dysfunction,POCD)的特征性表现是麻醉和手术后认知功能的持续性下降.这种多认知领域的功能需要感觉和广泛的神经学检测来评估,由于不同的检测仪器、不同的时间点和应用不同的统计学方法,因而对POCD一直没有统一的定义,各POCD间的研究也缺乏比较性.因此,进一步阐述POCD的影响因素及发病机制,有利于对POCD的研究建立标准的检测、诊断和防治方法.

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

    NARCIS (Netherlands)

    van Zutphen, Tim; Ciapaite, Jolita; Bloks, Vincent W.; Ackereley, Cameron; Gerding, Albert; Jurdzinski, Angelika; Allgayer de Moraes, Roberta; 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

    2016-01-01

    BACKGROUND & AIMS: 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 produc

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

    NARCIS (Netherlands)

    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.

    2016-01-01

    Background & Aims: 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 produc

  16. 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

  17. 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 (p<0.036, effect size 0.51). In the PE group, 'accuracy index of attention domain showed greater improvement than TAU alone at 6-month follow-up (p<0.025, effect size 0.61). For several other cognitive domains, significant improvements were observed with YT or PE compared with TAU alone (p<0.05, effect sizes 0.30-1.97). Both YT and PE improved attention 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.

  18. Assessment of Dysfunctional Cognitions in Binge-Eating Disorder: Factor Structure and Validity of the Mizes Anorectic Cognitions Questionnaire-Revised (MAC-R)

    Science.gov (United States)

    Carrard, Isabelle; Rothen, Stephane; Kruseman, Maaike; Khazaal, Yasser

    2017-01-01

    Background: Dysfunctional cognitions regarding weight and shape and their implications for self-esteem are considered core features of anorexia nervosa and bulimia nervosa. However, they have also been associated with the severity of binge eating disorder (BED). Therefore, they should be screened with appropriate instruments to tailor treatment to individual patient needs. The Mizes Anorectic Cognitions-Revised (MAC-R) is a self-report questionnaire that lists dysfunctional cognitions related to three hypothesized core beliefs typical of the psychopathology of eating disorders: weight and eating as the basis of approval from others; the belief that rigid self-control is fundamental to self-worth; and the rigidity of weight- and eating-regulation efforts. Objectives: The goal of the study was to confirm the factor structure and to assess the validity of the MAC-R among a sample that met full-threshold and subthreshold criteria for BED. Methods: We used data of women meeting full-threshold (n = 94) and subthreshold (n = 22) criteria for BED to conduct confirmatory factor analyses and to compute Spearman's correlations, in order to assess factorial, convergent, and discriminant validity. Results: Two models having a structure of three factors with or without a total score proved to be acceptable. The MAC-R total score was correlated with questionnaires assessing dimensions related to eating disorder psychopathology, adding to the validity of the questionnaire. Conclusion: These results were similar to those found in studies on the psychometric properties of the MAC among samples with anorexia nervosa or bulimia nervosa, encouraging the use of the MAC-R as a research or clinical tool in order to further document the core beliefs underlying BED. PMID:28261139

  19. Assessment of Dysfunctional Cognitions in Binge-Eating Disorder: Factor Structure and Validity of the Mizes Anorectic Cognitions Questionnaire-Revised (MAC-R).

    Science.gov (United States)

    Carrard, Isabelle; Rothen, Stephane; Kruseman, Maaike; Khazaal, Yasser

    2017-01-01

    Background: Dysfunctional cognitions regarding weight and shape and their implications for self-esteem are considered core features of anorexia nervosa and bulimia nervosa. However, they have also been associated with the severity of binge eating disorder (BED). Therefore, they should be screened with appropriate instruments to tailor treatment to individual patient needs. The Mizes Anorectic Cognitions-Revised (MAC-R) is a self-report questionnaire that lists dysfunctional cognitions related to three hypothesized core beliefs typical of the psychopathology of eating disorders: weight and eating as the basis of approval from others; the belief that rigid self-control is fundamental to self-worth; and the rigidity of weight- and eating-regulation efforts. Objectives: The goal of the study was to confirm the factor structure and to assess the validity of the MAC-R among a sample that met full-threshold and subthreshold criteria for BED. Methods: We used data of women meeting full-threshold (n = 94) and subthreshold (n = 22) criteria for BED to conduct confirmatory factor analyses and to compute Spearman's correlations, in order to assess factorial, convergent, and discriminant validity. Results: Two models having a structure of three factors with or without a total score proved to be acceptable. The MAC-R total score was correlated with questionnaires assessing dimensions related to eating disorder psychopathology, adding to the validity of the questionnaire. Conclusion: These results were similar to those found in studies on the psychometric properties of the MAC among samples with anorexia nervosa or bulimia nervosa, encouraging the use of the MAC-R as a research or clinical tool in order to further document the core beliefs underlying BED.

  20. 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.

  1. 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

  2. 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

    2016-08-05

    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.

  3. Duration of thyroid dysfunction correlates with all-cause mortality. the OPENTHYRO Register Cohort.

    Directory of Open Access Journals (Sweden)

    Anne Sofie Laulund

    Full Text Available 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 mortality. METHODS: Register-based follow-up study of 239,768 individuals with a serum TSH measurement from hospitals and/or general practice in Funen, Denmark. Measurements were performed at a single laboratory from January 1st 1995 to January 1st 2011. Cox regression was used for mortality analyses and Charlson Comorbidity Index (CCI was used as comorbidity score. RESULTS: Hazard ratios (HR with 95% confidence intervals (CI for mortality with decreased (4.0 mIU/L levels of TSH were 2.22; 2.14-2.30; P<0.0001 and 1.28; 1.22-1.35; P<0.0001, respectively. Adjusting for age, gender, CCI and diagnostic setting attenuated the risk estimates (HR 1.23; 95% CI: 1.19-1.28; P<0.0001, mean follow-up time 7.7 years, and HR 1.07; 95% CI: 1.02-1.13; P = 0.004, mean follow-up time 7.2 years for decreased and elevated values of TSH, respectively. Mortality risk increased by a factor 1.09; 95% CI: 1.08-1.10; P<0.0001 or by a factor 1.03; 95% CI: 1.02-1.04; P<0.0001 for each six months a patient suffered from decreased or elevated TSH, respectively. Subdividing according to degree of thyroid dysfunction, overt hyperthyroidism (HRovert 1.12; 95% CI: 1.06-1.19; P<0.0001, subclinical hyperthyroidism (HRsubclinical 1.09; 95% CI: 1.02-1.17; P = 0.02 and overt hypothyroidism (HRovert 1.57; 95% CI: 1.34-1.83; P<0.0001, but not subclinical hypothyroidism (HRsubclinical 1.03; 95% CI: 0.97-1.09; P = 0.4 were associated with increased mortality. CONCLUSIONS AND RELEVANCE: In a large-scale, population-based cohort with long-term follow-up (median 7.4 years, overt and subclinical hyperthyroidism and overt but not subclinical hypothyroidism were associated with increased

  4. 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

    BACKGROUND: There is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed...... to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder. METHODS: In this 4-week, pilot, open-label, domain-based study (e.g. cognition), we recruited 19 individuals with major depressive disorder (MDD......) or bipolar disorder (BD) and an impairment in executive function, defined as a below-average performance in the Trail Making Test-B (TMTB). Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy. RESULTS: Participants had significant increases from baseline to week 4 in the TMTB standard...

  5. Subjective cognitive dysfunction in first-episode and chronic schizophrenic patients.

    Science.gov (United States)

    Moritz, S; Lambert, M; Andresen, B; Böthern, A; Naber, D; Krausz, M

    2001-01-01

    Previous studies indicate that first-episode and chronic schizophrenic patients do not differ regarding neuropsychological performance as assessed with standard cognitive tasks. For the present study, it was investigated whether first-episode and chronic schizophrenics report similar subjective cognitive deficits. The Frankfurt Complaint Questionnaire (FCQ), a scale devised for assessing subjective cognitive disturbances in schizophrenia, was administered to 20 first-episode and 36 chronic schizophrenic patients, as well as 20 healthy controls. The schizophrenic subsamples did not differ on any of the FCQ subscales or on a "lie scale," measuring illness denial. Psychopathological ratings were comparable for both groups. As expected, healthy subjects reported significantly less cognitive and perceptual problems than schizophrenic patients. In marked contrast to a Kraepelinian view of schizophrenia, the present data confirm previous studies conducted with objective neuropsychological tests that schizophrenia is a neurodevelopmental rather than a neurodegenerative disorder.

  6. Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway

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    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

  7. 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. PMID:26903935

  8. 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

  9. 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.

  10. 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.

  11. 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  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.

  12. 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.

  13. Brain dysfunction in phenylketonuria : Is phenylalanine toxicity the only possible cause?

    NARCIS (Netherlands)

    van Spronsen, F. J.; Hoeksma, Marieke; Reijngoud, Dirk-Jan

    In phenylketonuria, mental retardation is prevented by a diet that severely restricts natural protein and is supplemented with a phenylalanine-free amino acid mixture. The result is an almost normal outcome, although some neuropsychological disturbances remain. The pathology underlying cognitive

  14. Brain dysfunction in phenylketonuria : Is phenylalanine toxicity the only possible cause?

    NARCIS (Netherlands)

    van Spronsen, F. J.; Hoeksma, Marieke; Reijngoud, Dirk-Jan

    2009-01-01

    In phenylketonuria, mental retardation is prevented by a diet that severely restricts natural protein and is supplemented with a phenylalanine-free amino acid mixture. The result is an almost normal outcome, although some neuropsychological disturbances remain. The pathology underlying cognitive dys

  15. 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

  16. 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

  17. Left coronary artery stenosis causing left ventricular dysfunction in two children with supravalvular aortic stenosis.

    Science.gov (United States)

    Yildiz, Okan; Altin, Firat H; Kaya, Mehmet; Ozyılmaz, Isa; Guzeltas, Alper; Erek, Ersin

    2015-04-01

    Congenital supravalvar aortic stenosis (SVAS) is an arteriopathy associated with Williams-Beuren syndrome (WBS) and other isolated elastin gene deletions. Cardiovascular manifestations associated with WBS are characterized by obstructive arterial lesions such as SVAS and pulmonary artery stenosis in addition to bicuspid aortic valve and mitral valve prolapse. However, coronary artery ostial stenosis may be associated with SVAS, and it increases the risk of sudden death and may complicate surgical management. In this report, we present our experience with two patients having SVAS and left coronary artery ostial stenosis with associated left ventricular dysfunction. © The Author(s) 2014.

  18. Reversible Cognitive Frailty, Dementia, and All-Cause Mortality. The Italian Longitudinal Study on Aging.

    Science.gov (United States)

    Solfrizzi, Vincenzo; Scafato, Emanuele; Seripa, Davide; Lozupone, Madia; Imbimbo, Bruno P; D'Amato, Angela; Tortelli, Rosanna; Schilardi, Andrea; Galluzzo, Lucia; Gandin, Claudia; Baldereschi, Marzia; Di Carlo, Antonio; Inzitari, Domenico; Daniele, Antonio; Sabbà, Carlo; Logroscino, Giancarlo; Panza, Francesco

    2017-01-01

    Cognitive frailty, a condition describing the simultaneous presence of physical frailty and mild cognitive impairment, has been recently defined by an international consensus group. We estimated the predictive role of a "reversible" cognitive frailty model on incident dementia, its subtypes, and all-cause mortality in nondemented older individuals. We verified if vascular risk factors or depressive symptoms could modify this predictive role. Longitudinal population-based study with 3.5- and 7-year of median follow-up. Eight Italian municipalities included in the Italian Longitudinal Study on Aging. In 2150 older individuals from the Italian Longitudinal Study on Aging, we operationalized reversible cognitive frailty with the presence of physical frailty and pre-mild cognitive impairment subjective cognitive decline, diagnosed with a self-report measure based on item 14 of the Geriatric Depression Scale. Incidence of dementia, its subtypes, and all-cause mortality. Over a 3.5-year follow-up, participants with reversible cognitive frailty showed an increased risk of overall dementia [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.02-5.18], particularly vascular dementia (VaD), and all-cause mortality (HR 1.74, 95% CI 1.07-2.83). Over a 7-year follow-up, participants with reversible cognitive frailty showed an increased risk of overall dementia (HR 2.12, 95% CI 1.12-4.03), particularly VaD, and all-cause mortality (HR 1.39, 95% CI 1.03-2.00). Vascular risk factors and depressive symptoms did not have any effect modifier on the relationship between reversible cognitive frailty and incident dementia and all-cause mortality. A model of reversible cognitive frailty was a short- and long-term predictor of all-cause mortality and overall dementia, particularly VaD. The absence of vascular risk factors and depressive symptoms did not modify the predictive role of reversible cognitive frailty on these outcomes. Copyright © 2016 AMDA – The Society for Post-Acute and

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

    DEFF Research Database (Denmark)

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

    , the temporal pole, and posterior cingulate gyrus in patients. In addition we found widespread negative correlations between RTH and mini-mental state examination (MMSE) scores in all major lobes except the occipital lobe (figure). Conclusions: The widespread negative correlation between RTH and MMSE...... is consistent with the capillary dysfunction hypothesis of AD. High capillary transit time heterogeneity is hypothesized to limit the oxygen availability to the tissue....

  20. 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.

  1. 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

  2. Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death.

    Science.gov (United States)

    Parker, J A; Connolly, J B; Wellington, C; Hayden, M; Dausset, J; Neri, C

    2001-11-06

    Huntington's disease (HD) is a dominant neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt). HD pathogenesis appears to involve the production of mutated N-terminal htt, cytoplasmic and nuclear aggregation of htt, and abnormal activity of htt interactor proteins essential to neuronal survival. Before cell death, neuronal dysfunction may be an important step of HD pathogenesis. To explore polyQ-mediated neuronal toxicity, we expressed the first 57 amino acids of human htt containing normal [19 Gln residues (Glns)] and expanded (88 or 128 Glns) polyQ fused to fluorescent marker proteins in the six touch receptor neurons of Caenorhabditis elegans. Expanded polyQ produced touch insensitivity in young adults. Noticeably, only 28 +/- 6% of animals with 128 Glns were touch sensitive in the tail, as mediated by the PLM neurons. Similar perinuclear deposits and faint nuclear accumulation of fusion proteins with 19, 88, and 128 Glns were observed. In contrast, significant deposits and morphological abnormalities in PLM cell axons were observed with expanded polyQ (128 Glns) and partially correlated with touch insensitivity. PLM cell death was not detected in young or old adults. These animals indicate that significant neuronal dysfunction without cell death may be induced by expanded polyQ and may correlate with axonal insults, and not cell body aggregates. These animals also provide a suitable model to perform in vivo suppression of polyQ-mediated neuronal dysfunction.

  3. 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.

  4. 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.

  5. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Emily Banks

    Full Text Available BACKGROUND: Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes. METHODS AND FINDINGS: We conducted a prospective population-based Australian study (the 45 and Up Study linking questionnaire data from 2006-2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality. Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31-1.95, heart failure (8.00, 2.64-24.2, peripheral vascular disease (1.92, 1.12-3.29, "other" CVD (1.26, 1.05-1.51, all CVD combined (1.35, 1.19-1.53, and all-cause mortality (1.93, 1.52-2.44. For men with previous CVD, corresponding RRs (95% CI were 1.70 (1.46-1.98, 4.40 (2.64-7.33, 2.46 (1.63-3.70, 1.40 (1.21-1.63, 1.64 (1.48-1.81, and 2.37 (1.87-3.01, respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22-2.26, atrioventricular and left bundle branch

  6. The THINC-Integrated Tool (THINC-it) Screening Assessment for Cognitive Dysfunction: Validation in Patients With Major Depressive Disorder.

    Science.gov (United States)

    McIntyre, Roger S; Best, Michael W; Bowie, Christopher R; Carmona, Nicole E; Cha, Danielle S; Lee, Yena; Subramaniapillai, Mehala; Mansur, Rodrigo B; Barry, Harry; Baune, Bernhard T; Culpepper, Larry; Fossati, Philippe; Greer, Tracy L; Harmer, Catherine; Klag, Esther; Lam, Raymond W; Wittchen, Hans-Ulrich; Harrison, John

    2017-07-01

    To validate the THINC-integrated tool (THINC-it)-a freely available, patient-administered, computerized screening tool integrating subjective and objective measures of cognitive function in adults with major depressive disorder (MDD). Subjects aged 18 to 65 years (n = 100) with recurrent MDD experiencing a major depressive episode of at least moderate severity were evaluated and compared to age-, sex-, and education-matched healthy controls (n = 100). Between January and June 2016, subjects completed the THINC-it, which includes variants of the Choice Reaction Time Identification Task (IDN), One-Back Test, Digit Symbol Substitution Test, Trail Making Test-Part B, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). The THINC-it required approximately 10 to 15 minutes for administration and was capable of detecting cognitive deficits in adults with MDD. A total of 44.4% of adults with MDD exhibited cognitive performance at ≥ 1.0 SD below that of healthy controls on standardized mean scores of the THINC-it. Concurrent validity of the overall tool, based on a calculated composite score, was acceptable (r = 0.539, P < .001). Concurrent validity of the component tests ranged from -0.083 (IDN) to 0.929 (PDQ-5-D). Qualitative survey results indicated that there was a high level of satisfaction and perceived value in administering the THINC-it regarding its impact on the appropriateness and quality of care being received. The THINC-it is a valid and sensitive tool for detecting cognitive dysfunction in adults with MDD that is free, easy to use, and rapidly administered. The THINC-it should be incorporated into the assessment and measurement of all patients with MDD, particularly among those with enduring functional impairment. ClinicalTrials.gov identifier: NCT02508493.

  7. Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years.

    Science.gov (United States)

    Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Ron, Maria; Penny, Sophie; Thompson, Alan J; Ciccarelli, Olga

    2013-05-01

    We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability.

  8. 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.

  9. The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington's disease.

    Science.gov (United States)

    Polyzos, Aris A; McMurray, Cynthia T

    2017-01-01

    Mitochondrial dysfunction and ensuing oxidative damage is typically thought to be a primary cause of Huntington's disease, Alzheimer's disease, and Parkinson disease. There is little doubt that mitochondria (MT) become defective as neurons die, yet whether MT defects are the primary cause or a detrimental consequence of toxicity remains unanswered. Oxygen consumption rate (OCR) and glycolysis provide sensitive and informative measures of the functional status MT and the cells metabolic regulation, yet these measures differ depending on the sample source; species, tissue type, age at measurement, and whether MT are measured in purified form or in a cell. The effects of these various parameters are difficult to quantify and not fully understood, but clearly have an impact on interpreting the bioenergetics of MT or their failure in disease states. A major goal of the review is to discuss issues and coalesce detailed information into a reference table to help in assessing mitochondrial dysfunction as a cause or consequence of Huntington's disease. Published by Elsevier B.V.

  10. Providencia alcalifaciens causes barrier dysfunction and apoptosis in tissue cell culture: potent role of lipopolysaccharides on diarrheagenicity.

    Science.gov (United States)

    Asakura, Hiroshi; Momose, Yoshika; Ryu, C-H; Kasuga, Fumiko; Yamamoto, Shigeki; Kumagai, Susumu; Igimi, Shizunobu

    2013-01-01

    Providencia alcalifaciens is a member of the Enterobacteriaceae family that occasionally causes diarrheagenic illness in humans via the intake of contaminated foods. Despite the epidemiological importance of P. alcalifaciens, little is known about its pathobiology. Here we report that P. alcalifaciens causes barrier dysfunction in Caco-2 cell monolayers and induces apoptosis in calf pulmonary artery endothelial cells. P. alcalifaciens infection caused a 30% reduction in transepithelial resistance in Caco-2 cell monolayers, which was greater than that for cells infected with Shigella flexneri or non-pathogenic Escherichia coli. As with viable bacteria, bacterial lysates treated with heat, benzonase or proteinase, but not with polymixin B, were also involved in the cellular response. TLR4 antibody neutralisation significantly restored the P. alcalifaciens-induced transepithelial resistance reduction in Caco-2 cells, suggesting that lipopolysaccharides (LPSs) might play a central role in this cellular response. Western blotting further indicated that P. alcalifaciens LPSs reduced occludin levels, whereas LPSs from Shigella or E. coli did not. Although the viability of Caco-2 cells was not altered significantly, the calf pulmonary artery endothelial cell line was highly sensitive to P. alcalifaciens infection. This sensitivity was indeed dependent on LPS, which induced rapid apoptosis. Together, these data show that P. alcalifaciens LPSs participate in epithelial barrier dysfunction and endothelial apoptosis. The findings give insight into the LPS-dependent cell signal events affecting diarrheagenicity during infection with P. alcalifaciens.

  11. The Challenges of Diagnosing Cognitive Dysfunction with Neuropsychiatric Systemic Lupus Erythematosus in Childhood.

    Science.gov (United States)

    AlE'ed, Ashwaq; Vega-Fernandez, Patricia; Muscal, Eyal; Hinze, Claas; Tucker, Lori B; Appenzeller, Simone; Bader-Meunier, Brigitte; Roth, Johannes; Torrente-Segarra, Vicenç; Klein-Gitelman, Marisa S; Levy, Deborah M; Roebuck-Spencer, Tresa; Brunner, Hermine

    2016-12-19

    The diagnosis of Neuropsychiatric systemic lupus erythematosus disease (NPSLE) is challenging. The Automated Neuropsychological Assessment Metrics (ANAM) has been shown to be an accessible and promising tool for evaluating possible NPSLE in adult and childhood lupus. In this review, we present information about the development and use of Ped-ANAM; the benefit of using Ped-ANAM in children with and without NPSLE in the assessment and follow up of their disease condition; and the correlation of Ped-ANAM to imaging studies such as magnetic resonance imaging (MRI). PedANAM was validated in children with cSLE in different studies. Cognitive performance can be a challenging clinical feature to efficiently assess. However, research with the Ped-ANAM has produced a Cognitive Performance Score (CPS) that allows for a reliable and efficient estimation of cognitive ability and the presence of cognitive limitations that children with cSLE may show. Compared with traditional neurocognitive assessment tools, Ped-ANAM-CPS offers a promising alternative to overcome the difficulties that practitioners previously faced. This article is protected by copyright. All rights reserved.

  12. Metacognitive capacity predicts severity of trauma-related dysfunctional cognitions in adults with posttraumatic stress disorder.

    Science.gov (United States)

    Davis, Louanne W; Leonhardt, Bethany L; Siegel, Alysia; Brustuen, Beth; Luedtke, Brandi; Vohs, Jennifer L; James, Alison V; Lysaker, Paul H

    2016-03-30

    Deficits in metacognition have been proposed as a barrier to adaptive responding to trauma. However, little is known about how different aspects of metacognitive capacity relate to responses to trauma and whether their potential link to such responses is independent of the overall level of psychopathology. To explore both issues, negative trauma-related cognitions about the self, the world, and self-blame, as measured by the Posttraumatic Cognitions Inventory (PTCI), were correlated with concurrent measures of depression, posttraumatic stress disorder symptoms, and two forms of metacognition; the Metacognitions questionnaire (MCQ-30), which focuses on specific thoughts, and the Metacognition Assessment Scale Abbreviated (MAS-A) which focuses on the degree to which persons can form complex representations of self and other. Participants were 51 veterans of the wars in Iraq and Afghanistan who had a PTSD diagnosis primarily involving a combat-related index trauma. Correlations revealed that being younger and more depressed were linked with greater levels of negative cognitions about self and the world. Lower levels of self-reflectivity on the MAS-A and higher levels of cognitive self-consciousness on the MCQ-30 were uniquely related to greater levels of self-blame even after controlling for age, level of depression, and PTSD. Implications for research and treatment are discussed.

  13. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1

    NARCIS (Netherlands)

    Omrani, A; van der Vaart, T; Mientjes, E; van Woerden, G M; Hojjati, M R; Li, K W; Gutmann, D H; Levelt, C N; Smit, A B; Silva, A J; Kushner, S A; Elgersma, Y

    2015-01-01

    Cognitive impairments are a major clinical feature of the common neurogenetic disease neurofibromatosis type 1 (NF1). Previous studies have demonstrated that increased neuronal inhibition underlies the learning deficits in NF1, however, the molecular mechanism underlying this cell-type specificity h

  14. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1

    NARCIS (Netherlands)

    Omrani, A; van der Vaart, T; Mientjes, E; van Woerden, G M; Hojjati, M R; Li, K W; Gutmann, D H; Levelt, C N; Smit, A B; Silva, A J; Kushner, S A; Elgersma, Y

    2015-01-01

    Cognitive impairments are a major clinical feature of the common neurogenetic disease neurofibromatosis type 1 (NF1). Previous studies have demonstrated that increased neuronal inhibition underlies the learning deficits in NF1, however, the molecular mechanism underlying this cell-type specificity

  15. Do patients with OCD and pathological gambling have similar dysfunctional cognitions

    NARCIS (Netherlands)

    G.E. Anholt; P.M.G. Emmelkamp; D.C. Cath; P. van Oppen; H. Nelissen; J.H. Smit

    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. T

  16. Cognitive Dysfunction Is Worse among Pediatric Patients with Bipolar Disorder Type I than Type II

    Science.gov (United States)

    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 =…

  17. Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction.

    Science.gov (United States)

    Dettwiler, S; McKee, T; Hadaya, K; Chappuis, F; van Delden, C; Moll, S

    2010-06-01

    Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

  18. Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats.

    Science.gov (United States)

    Shi, Chengmei; Yi, Duan; Li, Zhengqian; Zhou, Yongde; Cao, Yiyun; Sun, Yan; Chui, Dehua; Guo, Xiangyang

    2017-03-30

    Several animal studies demonstrated that the volatile anesthetic isoflurane could influence the blood-brain barrier (BBB) integrity, which involved the cognitive impairment. Increasing evidence has also shown that the receptor for advanced glycation end-products (RAGE) played a major role in maintaining the integrity of BBB. The present study aimed to determine whether the RAGE-specific antibody protects against BBB disruption and cognitive impairment induced by isoflurane exposure in aged rats. 108 aged rats were randomly divided into four groups: (1) control group (Control); (2) 4h of 2% isoflurane exposure group (ISO); (3) RAGE antibody (20μL, 2.5μg/μL) treated+4h of 2% isoflurane exposure group (anti-RAGE+ISO); (4) RAGE antibody (20μL, 2.5μg/μL) treated group (anti-RAGE). The isoflurane anesthesia resulted in the upregulation of hippocampal RAGE expression, disruption of BBB integrity, neuroinflammation, and beta-amyloid (Aβ) accumulation in aged rats. In addition, significant cognitive deficits in the Morris water maze test was also observed. The antibody pretreatment resulted in significant improvements in BBB integrity. Furthermore, the expression of RAGE and proinflammatory mediators, as well as, Aβ accumulation were attenuated. Moreover, the antibody administration attenuated the isoflurane-induced cognitive impairment in aged rats. These results demonstrate that RAGE signaling is involved in BBB damage after isoflurane exposure. Thus, the RAGE antibody represents a novel therapeutic intervention to prevent isoflurane-induced cognitive impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 高同型半胱氨酸血症与老年人认知功能障碍相关性研究%Correlation of high homocysteine and cognitive dysfunction in elderly patients

    Institute of Scientific and Technical Information of China (English)

    杨昊翔; 尹立勇; 崔志杰

    2011-01-01

    patients cataloged as the mild cognitive impairment and 45 dementia patients cataloged as the dementia group, and 100 individuals which were selected randomly from the remained 898 eases as control group. The conceivable risk factors which may affect patients' cognitive function included age, education, smoking history, alcohol abuse, hypertension, blood glucose, blood lipids and others. We inserted those conceivable factors to a non-conditional logistic regression analysis to prove that the homoeysteine was the eventual independent risk factor of cognitive dysfunction. Besides, comparison was made in homocysteine for the further study among mild cognitive dysfunction patients, dementia patients and the normal individuals. Results Through multiple regression analysis, we redressed the influence caused by age, education,smoking,alcohol,hypertension,blood sugar and blood lipids. So,it cames to the decision that high homocysteine was a risk factor to cognitive dysfunction and it was confirmed that high homocysteine level significantly correlated to the degree of cognitive dysfunction ( P <0.05). Mild cognitive impairment group: Hey (20.03±9.02) μmol/L; dementia group: Hcy(26. 11±13.29) μmol/L; The Hcy of dementia and mild cognitive impairment group was higher than that of the elderly normal control group (16.34 ± 6.76) μmol/L, and the difference was statistically significant ( P < 0.05). Conclusion High homocysteine is the risk factor of cognitive dysfunction of the elderly, and its level of both sides is significantly correlated with the degree of cognitive dysfunction.

  20. Effectiveness of a Cognitive Behavioral Therapy for Dysfunctional Eating among Patients Admitted for Bariatric Surgery: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    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.

  1. PSD-93 Attenuates Amyloid-β-Mediated Cognitive Dysfunction by Promoting the Catabolism of Amyloid-β.

    Science.gov (United States)

    Yu, Linjie; Liu, Yi; Yang, Hui; Zhu, Xiaolei; Cao, Xiang; Gao, Jun; Zhao, Hui; Xu, Yun

    2017-01-01

    Amyloid-β (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Postsynaptic density protein 93 (PSD-93) is a key scaffolding protein enriched at postsynaptic sites. The aim of the present study was to examine whether PSD-93 overexpression could alleviate Aβ-induced cognitive dysfunction in APPswe/PS1dE9 (APP/PS1) mice by reducing Aβ levels in the brain. The level of PSD-93 was significantly decreased in the hippocampus of 6-month-old APP/PS1 mice compared with that in wild-type mice. Following lentivirus-mediated PSD-93 overexpression, cognitive function, synaptic function, and amyloid burden were investigated. The open field test, Morris water maze test, and fear condition test revealed that PSD-93 overexpression ameliorated spatial memory deficits in APP/PS1 mice. The facilitation of long-term potentiation induction was observed in APP/PS1 mice after PSD-93 overexpression. The expression of somatostatin receptor 4 (SSTR4) and neprilysin was increased, while the amyloid plaque load and Aβ levels were decreased in the brains of APP/PS1 mice. Moreover, PSD-93 interacted with SSTR4 and affected the level of SSTR4 on cell membrane, which was associated with the ubiquitination. Together, these findings suggest that PSD-93 attenuates spatial memory deficits and decreases amyloid levels in APP/PS1 mice, which might be associated with Aβ catabolism, and overexpression of PSD-93 might be a potential therapy for AD.

  2. P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    Segundo J. Guzman

    2016-01-01

    Full Text Available ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer’s disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.

  3. Prenatal exposure to polycyclic aromatic hydrocarbons and cognitive dysfunction in children

    OpenAIRE

    Jedrychowski, Wiesław A.; Perera, Frederica P.; Camann, David; Spengler, John; Butscher, Maria; Mroz, Elzbieta; Majewska, Renata; Flak, Elżbieta; Jacek, Ryszard; Sowa, Agata

    2014-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced by combustion of fossil fuel and other organic materials. Both experimental animal and human studies have reported the harmful impacts of PAH compounds on fetal growth and neurodevelopment, including verbal IQ of children. Here, we have assessed the association between cognitive function of children and prenatal PAH exposures. The study is part of an ongoing, longitudinal investigation of the health effec...

  4. 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.

  5. Incidence and risk factors for postoperative cognitive dysfunction in older adults undergoing major noncardiac surgery: A prospective study.

    Science.gov (United States)

    Shoair, Osama A; Grasso Ii, Mario P; Lahaye, Laura A; Daniel, Ronsard; Biddle, Chuck J; Slattum, Patricia W

    2015-01-01

    Postoperative cognitive dysfunction (POCD) is a decline in cognitive function that occurs after surgery. The purpose of this study was to estimate the incidence and identify potential risk factors of POCD in older adults undergoing major noncardiac surgery. A total of 69 patients aged 65 years or older undergoing major noncardiac surgery were enrolled. Patients' cognitive function was assessed before and 3 months after surgery using a computerized neurocognitive battery. A nonsurgical control group of 54 older adults was recruited to adjust for learning effects from repeated administration of neurocognitive tests. Data about potential risk factors for POCD were collected before, during, and after surgery, including patient, medication, and surgery factors. The incidence of POCD was calculated using the Z-score method. A multivariable logistic regression model was used to identify risk factors for POCD. POCD was present in eleven patients (15.9%, 95% confidence interval [CI] = 7.3-24.6) 3 months after major noncardiac surgery. Carrying the apolipoprotein E4 (APOE4) genotype (odds ratio [OR] = 4.74, 95% CI = 1.09-22.19), using one or more highly anticholinergic or sedative-hypnotic drugs at home prior to surgery (OR = 5.64, 95% CI = 1.35-30.22), and receiving sevoflurane for anesthesia (OR = 6.43, 95% CI = 1.49-34.66) were associated with the development of POCD. POCD was observed in 15.9% of older adults after major noncardiac surgery. Risk factors for POCD in these patients were carrying the APOE4 genotype, using one or more highly anticholinergic or sedative-hypnotic drugs prior to surgery, and receiving sevoflurane for anesthesia.

  6. Brain Dysfunction as One Cause of CFS Symptoms Including Difficulty with Attention and Concentration

    Directory of Open Access Journals (Sweden)

    Benjamin H Natelson

    2013-05-01

    Full Text Available We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS patients into subgroups. To date, we have shown that stratifying based on the presence or absence of co-morbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres. We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group. Objective evidence of orthostatic intolerance may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms. We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly. Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each.

  7. 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.

  8. Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction.

    Science.gov (United States)

    Goetzman, Eric S; Alcorn, John F; Bharathi, Sivakama S; Uppala, Radha; McHugh, Kevin J; Kosmider, Beata; Chen, Rimei; Zuo, Yi Y; Beck, Megan E; McKinney, Richard W; Skilling, Helen; Suhrie, Kristen R; Karunanidhi, Anuradha; Yeasted, Renita; Otsubo, Chikara; Ellis, Bryon; Tyurina, Yulia Y; Kagan, Valerian E; Mallampalli, Rama K; Vockley, Jerry

    2014-04-11

    Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation enzyme whose expression in humans is low or absent in organs known to utilize fatty acids for energy such as heart, muscle, and liver. This study demonstrates localization of LCAD to human alveolar type II pneumocytes, which synthesize and secrete pulmonary surfactant. The physiological role of LCAD and the fatty acid oxidation pathway in lung was subsequently studied using LCAD knock-out mice. Lung fatty acid oxidation was reduced in LCAD(-/-) mice. LCAD(-/-) mice demonstrated reduced pulmonary compliance, but histological examination of lung tissue revealed no obvious signs of inflammation or pathology. The changes in lung mechanics were found to be due to pulmonary surfactant dysfunction. Large aggregate surfactant isolated from LCAD(-/-) mouse lavage fluid had significantly reduced phospholipid content as well as alterations in the acyl chain composition of phosphatidylcholine and phosphatidylglycerol. LCAD(-/-) surfactant demonstrated functional abnormalities when subjected to dynamic compression-expansion cycling on a constrained drop surfactometer. Serum albumin, which has been shown to degrade and inactivate pulmonary surfactant, was significantly increased in LCAD(-/-) lavage fluid, suggesting increased epithelial permeability. Finally, we identified two cases of sudden unexplained infant death where no lung LCAD antigen was detectable. Both infants were homozygous for an amino acid changing polymorphism (K333Q). These findings for the first time identify the fatty acid oxidation pathway and LCAD in particular as factors contributing to the pathophysiology of pulmonary disease.

  9. Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1

    Science.gov (United States)

    Giudice, Jimena; Xia, Zheng; Li, Wei; Cooper, Thomas A.

    2016-01-01

    The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development. RNA-sequencing of mRNA from homozygous neonatal hearts identified a network of cell cycle genes significantly up-regulated and down-regulation of ion transport and circadian genes. Cell cycle genes are enriched for Celf1 binding sites supporting a regulatory role in mRNA stability of these transcripts. We also identified a cardiac splicing network coordinated by Celf1 depletion. Target events contain multiple Celf1 binding sites and enrichment in GU-rich motifs. Identification of direct Celf1 targets will advance our knowledge in the mechanisms behind developmental networks regulated by Celf1 and diseases where Celf1 is mis-regulated. PMID:27759042

  10. 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.

  11. Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles.

    Science.gov (United States)

    Priestley, Jessica R C; Buelow, Matthew W; McEwen, Scott T; Weinberg, Brian D; Delaney, Melanie; Balus, Sarah F; Hoeppner, Carlyn; Dondlinger, Lynn; Lombard, Julian H

    2013-09-01

    We investigated the effect of suppressing plasma angiotensin II (ANG II) levels on arteriolar relaxation in the hamster cheek pouch. Arteriolar diameters were measured via television microscopy during short-term (3-6days) high salt (HS; 4% NaCl) diet and angiotensin converting enzyme (ACE) inhibition with captopril (100mg/kg/day). ACE inhibition and/or HS diet eliminated endothelium-dependent arteriolar dilation to acetylcholine, endothelium-independent dilation to the NO donor sodium nitroprusside, the prostacyclin analogs carbacyclin and iloprost, and the KATP channel opener cromakalim; and eliminated arteriolar constriction during KATP channel blockade with glibenclamide. Scavenging of superoxide radicals and low dose ANG II infusion (25ng/kg/min, subcutaneous) reduced oxidant stress and restored arteriolar dilation in arterioles of HS-fed hamsters. Vasoconstriction to topically-applied ANG II was unaffected by HS diet while arteriolar responses to elevation of superfusion solution PO2 were unaffected (5% O2, 10% O2) or reduced (21% O2) by HS diet. These findings indicate that sustained exposure to low levels of circulating ANG II leads to widespread dysfunction in endothelium-dependent and independent vascular relaxation mechanisms in cheek pouch arterioles by increasing vascular oxidant stress, but does not potentiate O2- or ANG II-induced constriction of arterioles in the distal microcirculation of normotensive hamsters. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Chloroplast dysfunction causes multiple defects in cell cycle progression in the Arabidopsis crumpled leaf mutant.

    Science.gov (United States)

    Hudik, Elodie; Yoshioka, Yasushi; Domenichini, Séverine; Bourge, Mickaël; Soubigout-Taconnat, Ludivine; Mazubert, Christelle; Yi, Dalong; Bujaldon, Sandrine; Hayashi, Hiroyuki; De Veylder, Lieven; Bergounioux, Catherine; Benhamed, Moussa; Raynaud, Cécile

    2014-09-01

    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.

  13. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia

    Science.gov (United States)

    Kohl, Susanne; Zobor, Ditta; Chiang, Wei-Chieh; Weisschuh, Nicole; Staller, Jennifer; Menendez, Irene Gonzalez; Chang, Stanley; Beck, Susanne C; Garrido, Marina Garcia; Sothilingam, Vithiyanjali; Seeliger, Mathias W; Stanzial, Franco; Benedicenti, Francesco; Inzana, Francesca; Héon, Elise; Vincent, Ajoy; Beis, Jill; Strom, Tim M; Rudolph, Günther; Roosing, Susanne; den Hollander, Anneke I; Cremers, Frans P M; Lopez, Irma; Ren, Huanan; Moore, Anthony T; Webster, Andrew R; Michaelides, Michel; Koenekoop, Robert K; Zrenner, Eberhart; Kaufman, Randal J; Tsang, Stephen H; Wissinger, Bernd; Lin, Jonathan H

    2015-01-01

    Achromatopsia (ACHM) is an autosomal recessive disorder characterized by color blindness, photophobia, nystagmus and severely reduced visual acuity. Using homozygosity mapping and whole-exome and candidate gene sequencing, we identified ten families carrying six homozygous and two compound-heterozygous mutations in the ATF6 gene (encoding activating transcription factor 6A), a key regulator of the unfolded protein response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. Patients had evidence of foveal hypoplasia and disruption of the cone photoreceptor layer. The ACHM-associated ATF6 mutations attenuate ATF6 transcriptional activity in response to ER stress. Atf6−/− mice have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age. This new ACHM-related gene suggests a crucial and unexpected role for ATF6A in human foveal development and cone function and adds to the list of genes that, despite ubiquitous expression, when mutated can result in an isolated retinal photoreceptor phenotype. PMID:26029869

  14. Upregulation of RCAN1 causes Down syndrome-like immune dysfunction.

    Science.gov (United States)

    Martin, Katherine R; Layton, Daniel; Seach, Natalie; Corlett, Alicia; Barallobre, Maria Jose; Arbonés, Maria L; Boyd, Richard L; Scott, Bernadette; Pritchard, Melanie A

    2013-07-01

    People with Down syndrome (DS) are more susceptible to infections and autoimmune disease, but the molecular genetic basis for these immune defects remains undetermined. In this study, we tested whether increased expression of the chromosome 21 gene RCAN1 contributes to immune dysregulation. We investigated the immune phenotype of a mouse model that overexpresses RCAN1. RCAN1 transgenic (TG) mice exhibit T cell abnormalities that bear a striking similarity to the abnormalities described in individuals with DS. RCAN1-TG mice display T cell developmental defects in the thymus and peripheral immune tissues. Thymic cellularity is reduced by substantial losses of mature CD4 and CD8 thymocytes and medullary epithelium. In peripheral immune organs T lymphocytes are reduced in number and exhibit reduced proliferative capacity and aberrant cytokine production. These T cell defects are stem cell intrinsic in that transfer of wild type bone marrow into RCAN1-TG recipients restored medullary thymic epithelium and T cell numbers in the thymus, spleen and lymph nodes. However, bone marrow transplantation failed to improve T cell function, suggesting an additional role for RCAN1 in the non-haemopoietic compartment. RCAN1 therefore facilitates T cell development and function, and when overexpressed, may contribute to immune dysfunction in DS.

  15. 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.

  16. 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.)

  17. 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.

  18. Circulating microparticles from Crohn's disease patients cause endothelial and vascular dysfunctions.

    Directory of Open Access Journals (Sweden)

    Daniela Leonetti

    Full Text Available BACKGROUND: Microparticles (MPs are small vesicles released during cell activation or apoptosis. They are involved in coagulation, inflammation and vascular dysfunction in several diseases. We characterized circulating MPs from Crohn's Disease (CD patients and evaluated their effects on endothelial function and vascular reactivity after in vivo injection into mice. METHODS: Circulating MPs and their cellular origins were examined by flow cytometry from blood samples from healthy subjects (HS and inactive or active CD patients. MPs were intravenously injected into mice. After 24 hours, endothelial function and vascular reactivity were assessed. RESULTS: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD. Active CD patients compared to HS displayed increased total circulating MPs, pro-coagulant MPs and those from platelets, endothelium, erythrocytes, leukocytes, activated leukocytes and activated platelets. A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index. MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice aorta and flow-induced dilation in mice small mesenteric arteries, MPs from inactive CD patients being more effective than those from active patients. CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites. CONCLUSIONS: We provide evidence that MPs from CD patients significantly alter endothelial and vascular function and therefore, may play a role in CD pathophysiology, at least by contributing to uncontrolled vascular-dependent intestinal damage.

  19. Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice.

    Directory of Open Access Journals (Sweden)

    Pennapa Chonpathompikunlert

    Full Text Available Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8 mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.

  20. Abnormal tau induces cognitive impairment through two different mechanisms: synaptic dysfunction and neuronal loss.

    Science.gov (United States)

    Di, J; Cohen, L S; Corbo, C P; Phillips, G R; El Idrissi, A; Alonso, A D

    2016-02-18

    The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimer-like dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization to the nucleus. Induction of PH-Tau triggered neuronal death (60% in CA3), astrocytosis, and loss of the processes in CA1. These findings suggest, that phosphorylated tau is sufficient to induce neurodegeneration and that two different mechanisms can induce cognitive impairment depending on the levels of PH-Tau expression.

  1. The Process of the Treatment of Cognitive Dysfunction after Craniocerebral Trauma%颅脑外伤后认知功能障碍的治疗进展

    Institute of Scientific and Technical Information of China (English)

    江玥; 张安仁

    2015-01-01

    认知功能障碍是颅脑损伤后常见的功能障碍,可表现为注意力困难、记忆力降低、执行功能、推理、判断、思维等各种能力的缺失。脑外伤后认知功能障碍的程度与康复训练的疗效直接相关,本文回顾近年文献,从药物治疗、针灸治疗、中药治疗、高压氧疗法、重复经颅磁刺激、康复训练等方面总结颅脑外伤后认知功能障碍的治疗进展。%Cognitive dysfunction is a common dysfunction after craniocerebral trauma, which can be expressed as attention difficulty, memory reduc-tion and the lack of abilities such as executive function, reasoning, judgement and thinking. The degree of cognitive dysfunction after craniocerebral trauma is directly related to the efficacy of rehabilitation training, this article would review the literatures in recent years, summarize the process of treatment of cognitive dysfunction after craniocerebral trauma from aspects such as medication, acupuncture therapy, herbal medication, hyperbaric oxygenation therapy, repetitive transcranial magnetic stimulation and rehabilitation trainning.

  2. Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23

    NARCIS (Netherlands)

    Smeets, Cleo J. L. M.; Jezierska, Justyna; Watanabe, Hiroyuki; Duarri Pique, Anna; Fokkens, Michiel R.; Meijer, Michel; Zhou, Qin; Yakovleva, Tania; Boddeke, Erik; den Dunnen, Wilfred; van Deursen, Jan; Bakalkin, Georgy; Kampinga, Harm H.; van de Sluis, Bart; Verbeek, Dineke S.

    2015-01-01

    Spinocerebellar ataxia type 23 is caused by mutations in PDYN, which encodes the opioid neuropeptide precursor protein, prodynorphin. Prodynorphin is processed into the opioid peptides, a-neoendorphin, and dynorphins A and B, that normally exhibit opioid-receptor mediated actions in pain signalling

  3. 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

    ]. All-cause mortality was increased in overt and subclinical hyperthyroidism [age adjusted incidence rates of 16 and 15 per 1000 person-years, respectively; incidence rate ratios (IRRs) 1.25 [95% confidence interval (CI) 1.15-1.36] and 1.23 (95% CI 1.16-1.30)] compared with euthyroid (incidence rate...... of 12 per 1000 person-years). Risk of MACEs was elevated in overt and subclinical hyperthyroidism [IRRs 1.16 (95% CI 1.05-1.27) and 1.09 (95% CI 1.02-1.16)] driven by heart failure [IRRs 1.14 (95% CI 0.99-1.32) and 1.20 (95% CI 1.10-1.31)]. A reduction of all-cause mortality was observed in subclinical...... 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....

  4. Activated platelets from diabetic rats cause endothelial dysfunction by decreasing Akt/endothelial NO synthase signaling pathway.

    Directory of Open Access Journals (Sweden)

    Keiko Ishida

    Full Text Available Diabetes is associated with endothelial dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. The purpose of this study was to characterize circulating platelets in diabetes and clarify their effects on endothelial function. Male Wistar rats were injected with streptozotocin (STZ to induce diabetes. Each experiment was performed by incubating carotid arterial rings with platelets (1.65×10(7 cells/mL; 30 min isolated from STZ or control rats. Thereafter, the vascular function was characterized in isolated carotid arterial rings in organ bath chambers, and each expression and activation of enzymes involved in nitric oxide and oxidative stress levels were analyzed. Endothelium-dependent relaxation induced by acetylcholine was significantly attenuated in carotid arteries treated with platelets isolated from STZ rats. Similarly, treatment with platelets isolated from STZ rats significantly reduced ACh-induced Akt/endothelial NO synthase signaling/NO production and enhanced TXB2 (metabolite of TXA2, while CD61 (platelet marker and CD62P (activated platelet marker were increased in carotid arteries treated with platelets isolated from STZ rats. Furthermore, the platelets isolated from STZ rats decreased total eNOS protein and eNOS dimerization, and increased oxidative stress. These data provide direct evidence that circulating platelets isolated from diabetic rats cause dysfunction of the endothelium by decreasing NO production (via Akt/endothelial NO synthase signaling pathway and increasing TXA2. Moreover, activated platelets disrupt the carotid artery by increasing oxidative stress.

  5. Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

    Directory of Open Access Journals (Sweden)

    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.

  6. Methoxychlor causes mitochondrial dysfunction and oxidative damage in the mouse ovary.

    Science.gov (United States)

    Gupta, R K; Schuh, R A; Fiskum, G; Flaws, J A

    2006-11-01

    Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by causing ovarian atrophy, persistent estrous cyclicity, and antral follicle atresia (apoptotic cell death). Oxidative damage resulting from reactive oxygen species (ROS) generation has been demonstrated to lead to toxicant-induced cell death. Thus, this work tested the hypothesis that MXC causes oxidative damage to the mouse ovary and affects mitochondrial respiration in a manner that stimulates ROS production. For the in vitro experiments, mitochondria were collected from adult cycling mouse ovaries, treated with vehicle (dimethyl sulfoxide; DMSO) or MXC, and subjected to polarographic measurements of respiration. For the in vivo experiments, adult cycling CD-1 mice were dosed with either vehicle (sesame oil) or MXC for 20 days. After treatment, ovarian mitochondria were isolated and subjected to measurements of respiration and fluorimetric measurements of H2O2 production. Some ovaries were also fixed and processed for immunohistochemistry using antibodies for ROS production markers: nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHG). Ovaries from in vivo experiments were also used to measure the mRNA expression and activity of antioxidants such as Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX), and catalase (CAT). The results indicate that MXC significantly impairs mitochondrial respiration, increases production of H2O2, causes more staining for nitrotyrosine and 8-OHG in antral follicles, and decreases the expression and activity of SOD1, GPX, and CAT as compared to controls. Collectively, these data indicate that MXC inhibits mitochondrial respiration, causes ROS production, and decreases antioxidant expression and activity in the ovary, specifically in the antral follicles. Therefore, it is possible that MXC causes atresia of ovarian antral follicles by inducing oxidative stress through mitochondrial production of ROS.

  7. 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 Aβ1-42 mouse model of AD. Single intracerebroventricular injections of Aβ1-42 (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 Aβ1-42 injection significantly decreased the Aβ1-42-induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ1-42-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 Aβ1-42-treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by Aβ1-42 injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in Aβ1-42-treated mice. Our results suggest that fisetin has a potent neuroprotective effect against Aβ1-42-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.

  8. PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction.

    Science.gov (United States)

    Fast, Rikke; Rodell, Anders; Gjedde, Albert; Mouridsen, Kim; Alstrup, Aage K; Bjarkam, Carsten R; West, Mark J; Berendt, Mette; Møller, Arne

    2013-01-01

    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 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 group (n = 4) of healthy dogs with radioactively labeled PiB ([(11)C]PiB). Structural magnetic resonance imaging brain scans were obtained from each dog. Tracer washout analysis yielded parametric maps of PiB retention in brain. In the CCD group, dogs had significant retention of [(11)C]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 (AβPP). The 6E10 stain revealed intracellular material positive for Aβ or AβPP, or both, in Purkinje cells. The brains of the two groups of dogs did not have significantly different patterns of [(11)C]PiB binding, suggesting that the material detected with 6E10 is AβPP rather than Aβ. As the comparison with the histological images revealed no correlation between the [(11)C]PiB and Aβ and AβPP deposits in post-mortem brain, the marked intracellular staining implies intracellular involvement of amyloid processing in the dog brain. We conclude that PET maps of [(11)C]PiB retention in brain of dogs with CCD fundamentally differ from the images obtained in most humans with AD.

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

    Directory of Open Access Journals (Sweden)

    Rikke eFast

    2013-12-01

    Full Text Available 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 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 group (n=4 of healthy dogs with radioactively labeled PiB ([11C]PiB. Structural MRI brain scans were obtained from each dog. Tracer washout analysis yielded parametric maps of PIB retention in brain. In the CCD group, dogs had significant retention of [11C]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 (AβPP. The 6E10 stain revealed intracellular material positive for Aβ or AβPP, or both, in Purkinje cells. The brains of the two groups of dogs did not have significantly different patterns of [11C]PiB binding, suggesting that the material detected with 6E10 is AβPP rather than Aβ. As the comparison with the histological images revealed no correlation between the [11C]PiB and Aβ and AβPP deposits in post-mortem brain, the marked intracellular staining implies intracellular involvement of amyloid processing in the dog brain. We conclude that PET maps of [11C]PiB retention in brain of dogs with CCD fundamentally differ from the images obtained in most humans with AD.

  10. Protective Effect of Thunbergia laurifolia (Linn. on Lead Induced Acetylcholinesterase Dysfunction and Cognitive Impairment in Mice

    Directory of Open Access Journals (Sweden)

    Moe Pwint Phyu

    2013-01-01

    Full Text Available Thunbergia laurifolia (linn., TL, a natural phenolic compound, has been reported to have many benefits and medicinal properties. The current study ascertains the total phenolic content present in TL aqueous leaf extract and also examines the antioxidant ability of the extract in preserving acetylcholinesterase (AChE activity of mice exposed to lead in vivo and in vitro model. Mice were given lead acetate (Pb in drinking water (1 g/L together with TL 100 and 200 mg/kg/day. The result showed that Pb induced AChE dysfunction in both in vitro and in vivo studies. TL significantly prevented Pb induced neurotoxicity in a dose-dependent manner which was indicated by comparatively better performance of TL treated mice in Morris Water Maze Swimming Test and increased AChE activity in the tissue sample collected from the brains of these mice. TL also exhibited the greatest amount of phenolic content, which has a significant positive correlation with its antioxidant capacity (P<0.05. Taken together, these data suggested that the total phenolic compounds in TL could exhibit antioxidant and in part neuroprotective properties. It may play a potential treatment strategy for Pb contamination.

  11. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System

    Directory of Open Access Journals (Sweden)

    Qing-Qing Xu

    2016-01-01

    Full Text Available Sodium Tanshinone IIA sulfonate (STS is a derivative of Tanshinone IIA (Tan IIA. Tan IIA has been reported to possess neuroprotective effects against Alzheimer’s disease (AD. However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP- induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE and increased the activity of choline acetyltransferase (ChAT in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD and decreased the levels of malondialdehyde (MDA and reactive oxygen species (ROS in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3. STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

  12. Dysfunctional breathing and reaching one’s physiological limit as causes of exercise-induced dyspnoea

    Directory of Open Access Journals (Sweden)

    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.

  13. Restoration of glyoxalase enzyme activity precludes cognitive dysfunction in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    More, Swati S; Vartak, Ashish P; Vince, Robert

    2013-02-20

    Pathologically high brain levels of reactive dicarbonyls such as methylglyoxal or glyoxal initiate processes that lead ultimately to neurodegeneration, presented clinically as Alzheimer's disease and other cognitive or motor impairment disorders. Methylglyoxal and glyoxal result from glycolysis and normal metabolic pathways. Their reaction products with proteins (advanced glycation end products), and their primary chemical toxicities are both linked unequivocally to the primary pathologies of Alzheimer's disease, namely, amyloid plaques and neurofibrillary tangles. Generation of dicarbonyls is countered through the reduction of dicarbonyls by the glutathione-dependent glyoxalase enzyme system. Although glyoxalase-I is overexpressed in early and middle stages of Alzheimer's disease, glutathione depletion in the Alzheimer's afflicted brain cripples its efficacy. Due to the lack of a suitable pharmacological tool, the restoration of glyoxalase enzyme activity in pre-Alzheimer's or manifest Alzheimer's remains yet unvalidated as a means for anti-Alzheimer's therapy development. Disclosed herein are the results of a preclinical study into the therapeutic efficacy of ψ-GSH, a synthetic cofactor of glyoxalase, in mitigating Alzheimer's indicators in a transgenic mouse model (APP/PS1) that is predisposed to Alzheimer's disease. ψ-GSH administration completely averts the development of spatial mnemonic and long-term cognitive/cued-recall impairment. Amyloid β deposition and oxidative stress indicators are drastically reduced in the ψ-GSH-treated APP/PS1 mouse. ψ-GSH lacks discernible toxicity at strikingly high doses of 2000 mg/kg. The hypothesis that restoring brain glyoxalase activity would ameliorate neurogeneration stands validated, thus presenting a much needed new target for design of anti-Alzheimer's therapeutics. Consequently, ψ-GSH is established as a candidate for drug-development.

  14. Mitochondrial dysfunction due to Leber's hereditary optic neuropathy as a cause of visual loss during assessment for epilepsy surgery.

    Science.gov (United States)

    Niehusmann, Pitt; Surges, Rainer; von Wrede, Randi D; Elger, Christian E; Wellmer, Jörg; Reimann, Jens; Urbach, Horst; Vielhaber, Stefan; Bien, Christian G; Kunz, Wolfram S

    2011-01-01

    Assessment for epilepsy surgery may require invasive measures such as implantation of intracranial electrodes or the Wada test. These investigations are commonly well tolerated. However, complications, including visual disturbances of various etiologies, have been reported. Here we describe two patients with pharmacoresistant temporal lobe epilepsy (TLE) who displayed loss of vision in the context of presurgical assessment and in whom mutations associated with Leber's hereditary optic neuropathy (LHON) were detected. Genetic analysis revealed in one patient the frequent mitochondrial G11778A LHON mutation in ND4. In the second patient, the mitochondrial C4640A mutation in ND2 was detected. This rare LHON mutation enhanced the sensitivity of the patient's muscle and brain tissue to amobarbital, a known blocker of the mitochondrial respiratory chain. Mitochondrial dysfunction has been reported in epilepsy. Thus, the presence of LHON mutations can be a rare cause of visual disturbances in patients with epilepsy and may have predisposed to development of epilepsy.

  15. Oxidative stress causes renal dopamine D1 receptor dysfunction and salt-sensitive hypertension in Sprague-Dawley rats.

    Science.gov (United States)

    Banday, Anees A; Lau, Yuen-Sum; Lokhandwala, Mustafa F

    2008-02-01

    Renal dopamine plays an important role in maintaining sodium homeostasis and blood pressure (BP) during increased sodium intake. The present study was carried out to determine whether renal dopamine D1 receptor (D1R) dysfunction contributes to increase in salt sensitivity during oxidative stress. Male Sprague-Dawley rats, divided into various groups, received tap water (vehicle); 1% NaCl (high salt [HS]); L-buthionine sulfoximine (BSO), an oxidant; and HS plus BSO with or without Tempol, an antioxidant, for 12 days. Compared with vehicle, HS intake increased urinary dopamine production and decreased basal renal Na/K-ATPase activity but did not affect BP. BSO-treated rats exhibited oxidative stress and a mild increase in BP. In these rats, D1R expression and G protein coupling were reduced, and SKF38393, a D1R agonist, failed to inhibit Na/K-ATPase activity and promote sodium excretion. Concomitant administration of BSO and HS caused oxidative stress, D1R dysfunction, and a marked increase in BP. Although renal dopamine production was increased, it failed to reduce the basal Na/K-ATPase activity in these animals. Treatment of BSO plus HS rats with Tempol decreased oxidative stress and restored endogenous, as well as exogenous, D1R agonist-mediated Na/K-ATPase inhibition and normalized BP. In conclusion, during HS intake, the increased dopamine production via Na/K-ATPase inhibition prevents an increase in BP. During oxidative stress, D1R function is defective, and there is mild hypertension. However, in the presence of oxidative stress, HS intake causes marked elevation in BP, which results from a defective renal D1R function leading to the failure of dopamine to inhibit Na/K-ATPase and promote sodium excretion.

  16. Early involvement of lysosome dysfunction in the degeneration of cerebral cortical neurons caused by the lipid peroxidation product 4-hydroxynonenal.

    Science.gov (United States)

    Zhang, Shi; Eitan, Erez; Mattson, Mark P

    2017-03-01

    Free radical-mediated oxidative damage to proteins, lipids, and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy-lysosome pathway in rat primary cortical neurons. We found that HNE, at a concentration that causes apoptosis over a 48-72 h period, increases protein levels of LC3 II and p62 and within 1 and 4 h of exposure, respectively; LC3 II and p62 immunoreactive puncta were observed in the cytoplasm of HNE-treated neurons at 6 h. The extent of up-regulation of p62 and LC3 II in response to HNE was not affected by co-treatment with the lysosome inhibitor bafilomycin A1, suggesting that the effects of HNE on autophagy were secondary to lysosome inhibition. Indeed, we found that neurons exposed to HNE exhibit elevated pH levels, and decreased protein substrate hydrolysis and cathepsin B activity. Neurons exposed to HNE also exhibited the accumulation of K63-linked polyubiquitinated proteins, which are substrates targeted for lysosomal degradation. Moreover, we found that the levels of LAMP2a and constitutively active heat-shock protein 70, and numbers of LAMP2a-positive lysosomes, are decreased in neurons exposed to HNE. Our findings demonstrate that the lipid peroxidation product HNE causes early impairment of lysosomes which may contribute to the accumulation of damaged and dysfunctional proteins and organelles and consequent neuronal death. Because impaired lysosome function is increasingly recognized as an early event in the neuronal death that occurs in neurodegenerative

  17. Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial.

    Science.gov (United States)

    Geng, Ying-Jie; Wu, Qing-Hua; Zhang, Rui-Qin

    2017-05-01

    To compare the incidence of postoperative cognitive dysfunction (POCD) in elderly surgical patients (>60years) receiving different anesthetics (propofol, sevoflurane, or isoflurane) and to identify potential biomarkers of POCD in this patient population. Prospective, randomized, double-blind clinical trial. University-affiliated teaching hospital. One hundred and fifty elderly patients scheduled for laparoscopic cholecystectomy. Elderly patients undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol, sevoflurane, or isoflurane anesthesia. Cognitive function was assessed using neuropsychological tests at baseline (1day before surgery [D0]), and on postoperative day 1 (D1) and day 3 (D3). Plasma S-100β and Aβ1-40 protein, IL-1β, IL-6 and TNF-α concentrations were assessed before induction of anesthesia (T0), after extubation (T1), and 1h (T2) and 24h (T3) postoperatively. The incidence of POCD was significantly lower in the propofol group compared to the isoflurane group and the sevoflurane group at D1 and D3 (propofol vs. isoflurane: D1 and D3, Ppropofol vs. sevoflurane: D1, P=0.012; D3, P=0.013). The incidence of POCD was significantly lower in the sevoflurane group compared to the isoflurane group at D1 (P=0.041), but not at D3. Postoperatively, plasma S-100β and Aβ1-40 protein, IL-1β, IL-6, and TNF-α concentrations were significantly decreased in the propofol group compared to the isoflurane group. Propofol anesthesia may be an option for elderly surgical patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

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    Nutchareeporn Nillert

    2017-01-01

    Full Text Available Neuroinflammation is pathological evidence of Alzheimer’s disease (AD that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β and tumor necrosis factor-α (TNFα, which may lead to neuronal damage and eventual death. Aged garlic extract (AGE has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight, orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42 into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats.

  19. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

    Science.gov (United States)

    Nillert, Nutchareeporn; Pannangrong, Wanassanun; Welbat, Jariya Umka; Chaijaroonkhanarak, Wunnee; Sripanidkulchai, Kittisak; Sripanidkulchai, Bungorn

    2017-01-01

    Neuroinflammation is pathological evidence of Alzheimer’s disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42)-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight), orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42) into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR) test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats. PMID:28054940

  20. Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients: A Longitudinal Study.

    Science.gov (United States)

    Chai, Chao; Wang, Zhiye; Fan, Linlin; Zhang, Mengjie; Chu, Zhiqiang; Zuo, Chao; Liu, Lei; Mark Haacke, E; Guo, Wenmei; Shen, Wen; Xia, Shuang

    2016-03-01

    The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs).Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups with and without CMBs. In the CMB group, 8 of 33 patients did not have a mini-mental state examination (MMSE) because of blurred vision. Multiple logistic regression was used to investigate the risk factors for CMBs. Partial correlation was used to explore the correlation between the increased number of CMBs and the change of MMSE scores.CMBs were seen in 33 (54%) hemodialysis patients. Both age and pre/postdialysis systolic blood pressure (SBP) positively correlated with CMBs. Serum iron (SI), and high-density lipoprotein cholesterol (HDL-c) negatively correlated with CMBs (all P CMBs and MMSE, 9 patients had scores CMBs in these patients were located in the brainstem and basal ganglia. Considering age and follow-up time as the co-confounding factors, the number of new CMBs over the 2 imaging time points negatively correlated with the change of MMSE scores (r = -0.673, P = 0.023).The presence of new CMBs was a risk factor for cognitive dysfunction and the location of CMBs may be correlated with cognitive impairment. Both SI and HDL-c were protective factors for the CMBs. The risk factors for CMBs included age, pre- and postdialysis SBP.

  1. Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients

    Science.gov (United States)

    Chai, Chao; Wang, Zhiye; Fan, Linlin; Zhang, Mengjie; Chu, Zhiqiang; Zuo, Chao; Liu, Lei; Mark Haacke, E.; Guo, Wenmei; Shen, Wen; Xia, Shuang

    2016-01-01

    Abstract The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs). Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups with and without CMBs. In the CMB group, 8 of 33 patients did not have a mini-mental state examination (MMSE) because of blurred vision. Multiple logistic regression was used to investigate the risk factors for CMBs. Partial correlation was used to explore the correlation between the increased number of CMBs and the change of MMSE scores. CMBs were seen in 33 (54%) hemodialysis patients. Both age and pre/postdialysis systolic blood pressure (SBP) positively correlated with CMBs. Serum iron (SI), and high-density lipoprotein cholesterol (HDL-c) negatively correlated with CMBs (all P CMBs and MMSE, 9 patients had scores CMBs in these patients were located in the brainstem and basal ganglia. Considering age and follow-up time as the co-confounding factors, the number of new CMBs over the 2 imaging time points negatively correlated with the change of MMSE scores (r = −0.673, P = 0.023). The presence of new CMBs was a risk factor for cognitive dysfunction and the location of CMBs may be correlated with cognitive impairment. Both SI and HDL-c were protective factors for the CMBs. The risk factors for CMBs included age, pre- and postdialysis SBP. PMID:27015171

  2. Loss of pRB causes centromere dysfunction and chromosomal instability.

    Science.gov (United States)

    Manning, Amity L; Longworth, Michelle S; Dyson, Nicholas J

    2010-07-01

    Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.

  3. Abnormalities of the DNA methylation mark and its machinery: an emerging cause of neurologic dysfunction.

    Science.gov (United States)

    Weissman, Jacqueline; Naidu, Sakkubai; Bjornsson, Hans T

    2014-07-01

    Recently, Mendelian disorders of the DNA methylation machinery have been described which demonstrate the complex roles of epigenetics in neurodevelopment and disease. For example, defects of DNMT1, the maintenance methyltransferase, lead to adult-onset progressive neurologic disorders, whereas defects of the de novo methyltransferases DNMT3A and DNMT3B lead to nonprogressive neurodevelopmental conditions. Furthermore, patients with DNMT3A deficiency demonstrate overgrowth, a feature common to disorders of histone machinery and imprinting disorders, highlighting the interconnectedness of the many epigenetic layers. Disorders of the DNA methylation machinery include both the aforementioned "writers" and also the "readers" of the methyl mark, such as MeCP2, the cause of Rett syndrome. Any dosage disruption, either haploinsufficiency or overexpression of DNA methylation machinery leads to widespread gene expression changes in trans, disrupting expression of a subset of target genes that contribute to individual disease phenotypes. In contrast, classical imprinting disorders such as Angelman syndrome have been thought generally to cause epigenetic dysregulation in cis. However, the recent description of multilocus methylation disorders challenges this generalization. Here, in addition to summarizing recent developments in identifying the pathogenesis of these diseases, we highlight clinical considerations and some unexpected therapeutic opportunities, such as topoisomerase inhibitors for classical imprinting disorders.

  4. Synergistical neuroprotection of rofecoxib and statins against malonic acid induced Huntington's disease like symptoms and related cognitive dysfunction in rats.

    Science.gov (United States)

    Kumar, Anil; Sharma, Neha; Mishra, Jitendriya; Kalonia, Harikesh

    2013-06-05

    Malonic acid (MA) is a reversible inhibitor of succinate dehydrogenase (SDH) which induces mitochondrial dysfunction followed by secondary excitotoxicity and apoptosis due to generation of reactive oxygen species. Therapeutic potential of rofecoxib and statins have been well documented in several experimental models of neurodegenerative disorders, however, its exact mechanism of action is not known properly. Therefore, the present study is an attempt to investigate the effect of rofecoxib along with the statins against MA induced behavioural and biochemical alterations in rats. Single intrastriatal MA (6 µmol) significantly caused motor incordination, memory dysfunction and alteration in the antioxidant enzyme levels, mitochondrial enzyme complex (I, II, IV) activities, mitochondrial redox ratio and pro-inflammatory cytokine [tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] levels in the striatum as compared to the naive group. Fourteen days treatment with rofecoxib, atorvastatin, simvastatin significantly attenuated these behavioural, biochemical, and cellular alterations as compared to control (MA treated group). However, the treatment of rofecoxib along with atorvastatin or simvastatin significantly attenuated these behavioural, biochemical, and cellular alterations as compared to their individual effects. The results of the present study demonstrated that rofecoxib modulates the protective effects of statins against MA-induced neurobehavioral and related biochemical and cellular alterations in rats. This further provides evidence toward the involvement of neuroinflammatory cascade in the pathogenesis of Huntington's disease.

  5. Executive dysfunction and gray matter atrophy in amnestic mild cognitive impairment.

    Science.gov (United States)

    Zheng, Dongming; Sun, Hongzan; Dong, Xiaoyu; Liu, Baiwei; Xu, Yongchuan; Chen, Sipan; Song, Lichun; Zhang, Hong; Wang, Xiaoming

    2014-03-01

    Recent studies have shown that impairment in executive function (EF) is common in patients with amnestic mild cognitive impairment (aMCI). However, the neuroanatomic basis of executive impairment in patients with aMCI remains unclear. In this study, multiple regression voxel-based morphometry analyses were used to examine the relationship between regional gray matter volumes and EF performance in 50 patients with aMCI and 48 healthy age-matched controls. The core EF components (response inhibition, working memory and task switching, based on the EF model of Miyake et al) were accessed with computerized tasks. Atrophic brain areas related to decreases in the three EF components in patients with aMCI were located in the frontal and temporal cortices. Within the frontal cortex, the brain region related to response inhibition was identified in the right inferior frontal gyrus. Brain regions related to working memory were located in the left anterior cingulate gyrus, left premotor cortex, and right inferior frontal gyrus, and brain regions related to task shifting were distributed in the bilateral frontal cortex. Atrophy in the right inferior frontal gyrus was most closely associated with a decrease in all three EF components in patients with aMCI. Our data, from the perspective of brain morphology, contribute to a better understanding of the role of these brain areas in the neural network of EF.

  6. 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).

  7. PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis

    Science.gov (United States)

    Ogata, Takehiro; Kasahara, Takeru; Nakanishi, Naohiko; Miyagawa, Kotaro; Naito, Daisuke; Hamaoka, Tetsuro; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

    2016-01-01

    Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. However, it remains unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here, we present a characterization of the hearts of PTRF/Cavin-1-null (PTRF−/−) mice. Electron microscopy revealed the reduction of caveolae in cardiomyocytes of PTRF−/− mice. PTRF−/− mice at 16 weeks of age developed a progressive cardiomyopathic phenotype with wall thickening of left ventricles and reduced fractional shortening evaluated by echocardiography. Electrocardiography revealed that PTRF−/− mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads. Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was also induced in PTRF−/− hearts. Western blotting analysis and quantitative RT-PCR revealed that Cav3 expression was suppressed in PTRF−/− hearts compared with that in wild-type (WT) ones. ERK1/2 was activated in PTRF−/− hearts compared with that in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and cardiomyopathy, which is partly attributable to Cav3 reduction in the heart. PMID:27612189

  8. Uric Acid Amplifies Aβ Amyloid Effects Involved in the Cognitive Dysfunction/Dementia: Evidences From an Experimental Model In Vitro.

    Science.gov (United States)

    Desideri, Giovambattista; Gentile, Roberta; Antonosante, Andrea; Benedetti, Elisabetta; Grassi, Davide; Cristiano, Loredana; Manocchio, Antonello; Selli, Sara; Ippoliti, Rodolfo; Ferri, Claudio; Borghi, Claudio; Giordano, Antonio; Cimini, Annamaria

    2017-05-01

    There is still a considerable debate concerning whether uric acid is neuroprotective or neurotoxic agent. To clarify this topic, we tested the effects of uric acid on neuronal cells biology by using differentiated SHSY5Y neuroblastoma cells incubated with amyloid β to reproduce an in vitro model of Alzheimer's disease. The incubation of cells with uric acid at the dose of 40 µM or higher significantly reduced cell viability and potentiated the proapoptotic effect of amyloid β. Finally, uric acid enhanced the generation of 4-hydroxynonenal and the expression of PPARβ/δ promoted by amyloid β, indicating a prooxidant effects. In conclusion, uric acid could exert a detrimental influence on neuronal biology being this influence further potentiated by the concomitant exposure to neurotoxic stimuli. This effect is evident for uric acid concentrations close to those achievable in cerebrospinal fluid in presence of mild hyperuricemia thus suggesting a potential role of uric acid in pathophysiology of cognitive dysfunction. These effects are influenced by the concentrations of uric acid and by the presence of favoring conditions that commonly occur in neurodegenerative disorders and well as in the aging brain, including increased oxidative stress and exposure to amyloid β. J. Cell. Physiol. 232: 1069-1078, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. The role of self-awareness and cognitive dysfunction in Parkinson's disease with and without impulse-control disorder.

    Science.gov (United States)

    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.

  10. The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: A sub-analysis of the MEMREHAB trial.

    Science.gov (United States)

    Chiaravalloti, Nancy D; DeLuca, John

    2015-10-01

    This study examined the influence of processing speed (PS) on benefit from treatment with the modified Story Memory Technique(©) (mSMT), a behavioral intervention shown to improve new learning and memory in multiple sclerosis (MS). This double-blind, placebo-controlled, randomized clinical trial included 85 participants with clinically definite MS, 45 assigned to the treatment group and 40 to the placebo-control group. Participants completed baseline and follow-up neuropsychological assessment. The present study represents a post-hoc analysis to examine the role of PS on treatment efficacy. The treatment group showed a significantly improved CVLT learning slope relative to the placebo group post-treatment, after co-varying PS performance. SDMT performance was a significant predictor of benefit from mSMT treatment, beyond group assignment. Post-hoc analysis indicated a significant correlation between the SDMT and overall cognition, indicating that the SDMT may be serving as a proxy for overall cognitive impairment. Performance on measures of cognitive dysfunction aside from learning and memory impact the benefit of mSMT treatment. While the current study focused on PS as a critical factor, PS may be serving as a marker for generalized cognitive dysfunction. Implications for cognitive rehabilitation in MS are discussed. © The Author(s), 2015.

  11. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation.

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P; Luthi-Carter, Ruth; Lowdell, Mark W; Björkqvist, Maria; Ostroff, Gary R; Aronin, Neil; Tabrizi, Sarah J

    2014-03-01

    Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.

  12. Insight into the mechanism of reproductive dysfunction caused by neonicotinoid pesticides.

    Science.gov (United States)

    Hoshi, Nobuhiko; Hirano, Tetsushi; Omotehara, Takuya; Tokumoto, Junko; Umemura, Yuria; Mantani, Youhei; Tanida, Takashi; Warita, Katsuhiko; Tabuchi, Yoshiaki; Yokoyama, Toshifumi; Kitagawa, Hiroshi

    2014-01-01

    Neonicotinoids, which were developed in the 1990 s as an insecticide having selective toxicity, were later found to cause reproductive abnormalities in experimental animals. In Japan there is an attempt to preserve endangered animals, including the Japanese crested ibis, and there is a question of whether neonicotinoids affect the reproduction of this bird, since they are used in its habitat. Hence, we investigated whether the daily oral administration of the neonicotinoid clothianidin (CTD) has any deleterious effects on the reproductive function of mature male only or both young male and female quails as experimental animals. Vacuolization and the number of germ cells having fragmented DNA in seminiferous tubules, as well as the number and size of vacuoles in hepatocytes, increased dose-dependently. The ovaries showed abnormal histology in the granulosa cells, which produce progesterone. There were significant differences in egg-laying rates and embryo weights between the groups. Glutathione Peroxidase 4 (GPx4) and Manganese Superoxide Dismutase (Mn-SOD), which protect the organism from oxidative damage, showed a dose-dependent decrease. Thus, it is possible neonicotinoids affect the bird's reproductive system through oxidative stress, reflecting an imbalance between the production of reactive oxygen species (ROS) and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. Responding to our study, Sado Island has since succeeded in breeding Japanese crested ibis in the wild without the use of neonicotinoids.

  13. Corticosteroids prevent acute lung dysfunction caused by thoracic irradiation in unanesthetized sheep

    Energy Technology Data Exchange (ETDEWEB)

    Loyd, J.E.; Bolds, J.M.; Wickersham, N.; Malcolm, A.W.; Brigham, K.L.

    1988-11-01

    We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H/sub 2/O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.

  14. Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction.

    Science.gov (United States)

    Reiner, Željko; Guardamagna, Ornella; Nair, Devaki; Soran, Handrean; Hovingh, Kees; Bertolini, Stefano; Jones, Simon; Ćorić, Marijana; Calandra, Sebastiano; Hamilton, John; Eagleton, Terence; Ros, Emilio

    2014-07-01

    Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. The age at onset and rate of progression vary greatly and this may relate to the nature of the underlying mutations. Patients presenting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age. Children and adults typically present with some combination of dyslipidaemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy. Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood. Given that these clinical manifestations are shared with other cardiovascular, liver and metabolic diseases, it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, endocrinologists, cardiologists and hepatologists on how to recognize individuals with this life-limiting disease. A diagnostic algorithm is proposed with a view to achieving definitive diagnosis using a recently developed blood test for lysosomal acid lipase. Finally, current management options are reviewed in light of the ongoing development of enzyme replacement therapy with sebelipase alfa (Synageva BioPharma Corp., Lexington, MA, USA), a recombinant human lysosomal acid lipase enzyme.

  15. Surgical incision-induced nociception causes cognitive impairment and reduction in synaptic NMDA receptor 2B in mice.

    Science.gov (United States)

    Zhang, Xiaoqin; Xin, Xin; Dong, Yuanlin; Zhang, Yiying; Yu, Buwei; Mao, Jianren; Xie, Zhongcong

    2013-11-06

    Postoperative cognitive dysfunction (POCD) is associated with impairments in daily functioning, and increased morbidity and mortality. However, the causes and neuropathogenesis of POCD remain largely unknown. Uncontrolled pain often occurs postoperatively. We therefore set out to determine the effects of surgical incision-induced nociception on the cognitive function and its underlying mechanisms in 3- and 9-month-old mice. The mice had surgical incision in the hindpaw and then were tested for nociceptive threshold, learning, and memory. Brain levels of NMDA receptor and cyclin-dependent kinase 5 (CDK5) were also assessed. We found that surgical incision-induced nociception in mice led to a decreased freezing time in the tone test (which assesses the hippocampus-independent learning and memory function), but not the context test, of Fear Conditioning System at 3 and 7 d, but not 30 d post incision in 9-month-old, but not 3-month-old mice. Consistently, the surgical incision selectively decreased synaptic NMDA receptor 2B levels in the medial prefrontal cortex, and increased levels of tumor necrosis factor-α and CDK5 in the cortex, but not hippocampus, of the mice. Finally, eutectic mixture of local anesthetics and CDK5 inhibitor, roscovitine, attenuated the surgical incision-induced reduction in the synaptic NMDA receptor 2B levels and learning impairment. These results suggested that surgical incision-induced nociception reduced the synaptic NMDA receptor 2B level in the medial prefrontal cortex of mice, which might lead to hippocampus-independent learning impairment, contributing to POCD. These findings call for further investigation to determine the role of surgical incision-induced nociception in POCD.

  16. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress.

    Science.gov (United States)

    Liang, S; Wang, T; Hu, X; Luo, J; Li, W; Wu, X; Duan, Y; Jin, F

    2015-12-03

    Increasing numbers of studies have suggested that the gut microbiota is involved in the pathophysiology of stress-related disorders. Chronic stress can cause behavioral, cognitive, biochemical, and gut microbiota aberrations. Gut bacteria can communicate with the host through the microbiota-gut-brain axis (which mainly includes the immune, neuroendocrine, and neural pathways) to influence brain and behavior. It is hypothesized that administration of probiotics can improve chronic-stress-induced depression. In order to examine this hypothesis, the chronic restraint stress depression model was established in this study. Adult specific pathogen free (SPF) Sprague-Dawley rats were subjected to 21 days of restraint stress followed by behavioral testing (including the sucrose preference test (SPT), elevated-plus maze test, open-field test (OFT), object recognition test (ORT), and object placement test (OPT)) and biochemical analysis. Supplemental Lactobacillus helveticus NS8 was provided every day during stress until the end of experiment, and selective serotonin reuptake inhibitor (SSRI) citalopram (CIT) served as a positive control. Results showed that L. helveticus NS8 improved chronic restraint stress-induced behavioral (anxiety and depression) and cognitive dysfunction, showing an effect similar to and better than that of CIT. L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels, and more hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression than in chronic stress rats. Taken together, these results indicate an anti-depressant effect of L. helveticus NS8 in rats subjected to chronic restraint stress depression and that this effect could be due to the microbiota-gut-brain axis. They also suggest the therapeutic potential of L. helveticus NS8 in stress-related and possibly other

  17. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Soo Lim

    Full Text Available There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ, is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48 were treated for 5 months with low concentrations (30 or 300 microg kg(-1 day(-1 of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent.

  18. Mycobacterium ulcerans infections cause progressive muscle atrophy and dysfunction, and mycolactone impairs satellite cell proliferation.

    Science.gov (United States)

    Houngbédji, Germain Mabèrou; Bouchard, Patrice; Frenette, Jérôme

    2011-03-01

    Clinical observations from Buruli ulcer (BU) patients in West Africa suggest that severe Mycobacterium ulcerans infections can cause skeletal muscle contracture and atrophy leading to significant impairment in function. In the present study, male mice C57BL/6 were subcutaneously injected with M. ulcerans in proximity to the right biceps muscle, avoiding direct physical contact between the infectious agent and the skeletal muscle. The histological, morphological, and functional properties of the muscles were assessed at different times after the injection. On day 42 postinjection, the isometric tetanic force and the cross-sectional area of the myofibers were reduced by 31% and 29%, respectively, in the proximate-infected muscles relative to the control muscles. The necrotic areas of the proximate-infected muscles had spread to 7% of the total area by day 42 postinjection. However, the number of central nucleated fibers and myogenic regulatory factors (MyoD and myogenin) remained stable and low. Furthermore, Pax-7 expression did not increase significantly in mycolactone-injected muscles, indicating that the satellite cell proliferation is abrogated by the toxin. In addition, the fibrotic area increased progressively during the infection. Lastly, muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (atrogin-1/MAFbx), two muscle-specific E3 ubiquitin ligases, were upregulated in the presence of M. ulcerans. These findings confirmed that skeletal muscle is affected in our model of subcutaneous infection with M. ulcerans and that a better understanding of muscle contractures and weakness is essential to develop a therapy to minimize loss of function and promote the autonomy of BU patients.

  19. Cholesterol homeostasis failure in the brain: implications for synaptic dysfunction and cognitive decline.

    Science.gov (United States)

    Segatto, Marco; Leboffe, Loris; Trapani, Laura; Pallottini, Valentina

    2014-01-01

    Cholesterol is one of the most important molecules in cell physiology because of its involvement in several biological processes: for instance, it determines both physical and biochemical properties of cell membranes and proteins. Disruption to cholesterol homeostasis leads to coronary heart disease, atherosclerosis and metabolic syndrome. Strong evidence suggests that cholesterol also has a crucial role in the brain as various neurological and neurodegenerative disorders, including Alzheimer's, Huntington's and Parkinson diseases are associated with disruptions to cholesterol homeostasis. Here, we summarize the current knowledge about the role cholesterol plays at synaptic junctions and the pathological consequences caused by disruptions in the homeostatic maintenance of this compound.

  20. Related factors and predictors of cognitive dysfunction in chronic kidney disease on maintenance hemodialysis in Nigeria

    Directory of Open Access Journals (Sweden)

    Lukman Femi Owolabi

    2016-01-01

    Full Text Available Background: Previous studies suggest a high frequency of cognitive impairment (CI in persons with chronic kidney disease (CKD; however, factors associated with CI and predictors of CI in persons with CKD remain largely unclear. The aim of this study was to determine the factors associated with CI and predictors of CI in CKD patients on maintenance hemodialysis. Materials and Methods: The first stage of the study included recruitment of 100 apparently healthy participants aimed at determining the reference values. The second stage of the study included eighty CKD patients on maintenance hemodialysis. The iron psychology (FEPSY was used to assess the memory, psychomotor speed, concentration, and attention using simple auditory reaction time (ART and visual reaction time (VRT tasks, recognition memory tests (RMT, finger tapping task (FTT, and binary choice task (BCT. Results: Using normative values generated in this study, 41 (51.3% and 43 (53.8% CKD patients had abnormal scores on ART dominant (D and nondominant (ND sides, respectively. Forty (50% and 42 (52.5% patients had abnormal scores on VRT D and ND sides, respectively. Twenty-one (26.3% and 68 (85% had abnormal scores on BCT and computer-assisted visual scanning task, respectively. Sixty-four (80% and 65 (81.3% had abnormal scores on RMT (words and RMT, respectively. Fifty-two (65% and 48 (60% patients had abnormal scores on D and ND sides of (FTT, respectively. Factors associated with psychomotor speed impairment were duration of CKD from diagnosis (P = 0.0001 and 0.043 in D and ND ART, respectively, duration on dialysis (P = 0.0001 across board in D and ND ART as well as in D and ND VRT, respectively, and plasma urea (PU and plasma creatinine (PCr (P < 0.05. Factors found to be associated with memory impairment included age (P = 0.045 and 0.025 on words and figures RMT, respectively, PU (P = 0.002 and 0.005 on words and figures RMT, respectively, and PCr (P = 0.012 and 0.040 on words and

  1. Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants.

    Science.gov (United States)

    Kutschera, J; Tomaselli, J; Maurer, U; Mueller, W; Urlesberger, B

    2005-03-01

    The objective of this study was to assess minor neurological dysfunction, cognitive development, and somatic development after dexamethasone therapy in very-low-birthweight infants. Thirty-three children after dexamethasone treatment were matched to 33 children without dexamethasone treatment. Data were assessed at the age of 3-7 years. Dexamethasone was started between the 7th and the 28th day of life over 7 days with a total dose of 2.35 mg/kg/day. Exclusion criteria were asphyxia, malformations, major surgical interventions, small for gestational age, intraventricular haemorrhage grades III and IV, periventricular leukomalacia, and severe psychomotor retardation. Each child was examined by a neuropediatrician for minor neurological dysfunctions and tested by a psychologist for cognitive development with a Kaufman Assessment Battery for Children and a Draw-a-Man Test. There were no differences in demographic data, growth, and socio-economic status between the two groups. Fine motor skills and gross motor function were significantly better in the control group (pdevelopment of speech, social development, and the Kaufman Assessment Battery for Children. After dexamethasone treatment, children showed a higher rate of minor neurological dysfunctions. Neurological development was affected even without neurological diagnosis. Further long-term follow-up studies will be necessary to fully evaluate the impact of dexamethasone on neurological and cognitive development.

  2. 电压门控性钾通道与认知功能障碍的研究进展%Voltage-gated potassium channels in cognitive dysfunction

    Institute of Scientific and Technical Information of China (English)

    颜文慧; 王萌(综述); 陈莉娜(审校)

    2015-01-01

    The growing number of cognitive dysfunction patients is bringing heavy mental and financial burdens to the society and families.Voltage-gated potassium channels (Kv), which consist of delayed rectifier potassium channels and transient outward po -tassium channels , are involved in the incidence of cognitive dysfunction .This review summarized the role of Kv channels in cognitive dysfunction and their relationship with N-methyl-D-aspartic acid receptors ( NMDARs) that play an important role in the process of learning and memory .%认知功能障碍患者的增多给社会、家庭带来了沉重的精神和经济负担。电压门控性钾通道( voltage-gated potas-sium channels, Kv)主要分为延迟整流钾通道和瞬时外向钾通道,参与认知功能障碍的发生。文中对Kv通道与认知功能障碍,以及Kv通道与在学习和记忆过程中起重要作用的N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体之间的关系作一综述。

  3. Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

    Science.gov (United States)

    Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

    2016-01-01

    The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented

  4. Hydrogen-rich saline attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels

    Science.gov (United States)

    Li, Cheng; Hou, Lengchen; Chen, Dan; Lin, Fuqing; Chang, Tao; Li, Mengzhu; Zhang, Lingling; Niu, Xiaoyin; Wang, Huiying; Fu, Shukun; Zheng, Junhua

    2017-01-01

    Objectives: The inhaled general anesthetic isoflurane has been shown to induce caspase-3 activation in vitro and in vivo. The underlying mechanisms and functional consequences of this activity remain unclear. Isoflurane can induce caspase-3 activation by causing accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and reduction in adenosine triphosphate (ATP) levels. This study aimed to investigate the protective effect of hydrogen, a novel antioxidant, against isoflurane-induced caspase-3 activation and cognitive impairment. Methods: H4 human neuroglioma cells overexpressing human amyloid precursor protein were treated with saline or hydrogen-rich saline (HS, 300 μM), with or without 2% isoflurane, for 6 h or 3 h. Western blot analysis, fluorescence assays, and a mitochondrial swelling assay were used to evaluate caspase-3 activation, levels of ROS and ATP, and mitochondrial function. The effect of the interaction of isoflurane (1.4% for 2 h) and HS (5 mL/kg) on cognitive function in mice was also evaluated using a fear conditioning test. Results: We found that HS attenuated isoflurane-induced caspase-3 activation. Moreover, HS treatment mitigated isoflurane-induced ROS accumulation, opening of mitochondrial permeability transition pores, reduction in mitochondrial membrane potential, and reduction in cellular ATP levels. Finally, HS significantly alleviated isoflurane-induced cognitive impairment in mice. Conclusions: Our results suggest that HS attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. These findings warrant further research into the underlying mechanisms of this activity, and indicate that HS has the potential to attenuate anesthesia neurotoxicity.

  5. Neuropsychological Testing and Machine Learning Distinguish Alzheimer’s Disease from Other Causes for Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    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.

  6. Neuropsychological Testing and Machine Learning Distinguish Alzheimer's Disease from Other Causes for Cognitive Impairment.

    Science.gov (United States)

    Gurevich, Pavel; Stuke, Hannes; Kastrup, Andreas; Stuke, Heiner; Hildebrandt, Helmut

    2017-01-01

    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.

  7. Respiratory dysfunction by AFG3L2 deficiency causes decreased mitochondrial calcium uptake via organellar network fragmentation

    Science.gov (United States)

    Maltecca, Francesca; De Stefani, Diego; Cassina, Laura; Consolato, Francesco; Wasilewski, Michal; Scorrano, Luca; Rizzuto, Rosario; Casari, Giorgio

    2012-01-01

    The mitochondrial protein AFG3L2 forms homo-oligomeric and hetero-oligomeric complexes with paraplegin in the inner mitochondrial membrane, named m-AAA proteases. These complexes are in charge of quality control of misfolded proteins and participate in the regulation of OPA1 proteolytic cleavage, required for mitochondrial fusion. Mutations in AFG3L2 cause spinocerebellar ataxia type 28 and a complex neurodegenerative syndrome of childhood. In this study, we demonstrated that the loss of AFG3L2 in mouse embryonic fibroblasts (MEFs) reduces mitochondrial Ca2+ uptake capacity. This defect is neither a consequence of global alteration in cellular Ca2+ homeostasis nor of the reduced driving force for Ca2+ internalization within mitochondria, since cytosolic Ca2+ transients and mitochondrial membrane potential remain unaffected. Moreover, experiments in permeabilized cells revealed unaltered mitochondrial Ca2+ uptake speed in Afg3l2−/− cells, indicating the presence of functional Ca2+ uptake machinery. Our results show that the defective Ca2+ handling in Afg3l2−/− cells is caused by fragmentation of the mitochondrial network, secondary to respiratory dysfunction and the consequent processing of OPA1. This leaves a number of mitochondria devoid of connections to the ER and thus without Ca2+ elevations, hampering the proper Ca2+ diffusion along the mitochondrial network. The recovery of mitochondrial fragmentation in Afg3l2−/− MEFs by overexpression of OPA1 rescues the impaired mitochondrial Ca2+ buffering, but fails to restore respiration. By linking mitochondrial morph