Li, Zhigui; Hao, Shuang; Yin, Hongqiang; Gao, Jing; Yang, Zhuo
The underlying mechanisms of cognitive impairment in diabetes remain incompletely characterized. Here we show that the autophagic inhibition by 3-methyladenine (3-MA) aggravates cognitive impairment in streptozotocin-induced diabetic mice, including exacerbation of anxiety-like behaviors and aggravation in spatial learning and memory, especially the spatial reversal memory. Further neuronal function identification confirmed that both long term potentiation (LTP) and depotentiation (DPT) were exacerbated by autophagic inhibition in diabetic mice, which indicating impairment of synaptic plasticity. However, no significant change of pair-pulse facilitation (PPF) was recorded in diabetic mice with autophagic suppression compared with the diabetic mice, which indicated that presynaptic function was not affected by autophagic inhibition in diabetes. Subsequent hippocampal neuronal cell death analysis showed that the apoptotic cell death, but not the regulated necrosis, significantly increased in autophagic suppression of diabetic mice. Finally, molecular mechanism that may lead to cell death was identified. The long non-coding RNA PVT1 (plasmacytoma variant translocation 1) expression was analyzed, and data revealed that PVT1 was decreased significantly by 3-MA in diabetes. These findings show that PVT1-mediated autophagy may protect hippocampal neurons from impairment of synaptic plasticity and apoptosis, and then ameliorates cognitive impairment in diabetes. These intriguing findings will help pave the way for exciting functional studies of autophagy in cognitive impairment and diabetes that may alter the existing paradigms.
Jin, Yang; Peng, Jian; Wang, Xiaona; Zhang, Dong; Wang, Tianyin
Bacterial endotoxin lipopolysaccharide (LPS) can induce systemic inflammation, and therefore disrupt learning and memory processes. Ginsenoside Rg1, a major bioactive component of ginseng, is shown to greatly improve cognitive function. The present study was designed to further investigate whether administration of ginsenoside Rg1 can ameliorate LPS-induced cognitive impairment in the Y-maze and Morris water maze (MWM) task, and to explore the underlying mechanisms. Results showed that exposure to LPS (500 μg/kg) significantly impaired working and spatial memory and that repeated treatment with ginsenoside Rg1 (200 mg/kg/day, for 30 days) could effectively alleviate the LPS-induced cognitive decline as indicated by increased working and spatial memory in the Y-maze and MWM tests. Furthermore, ginsenoside Rg1 treatment prevented LPS-induced decrease of acetylcholine (ACh) levels and increase of acetylcholinesterase (AChE) activity. Ginsenoside Rg1 treatment also reverted the decrease of alpha7 nicotinic acetylcholine receptor (α7 nAChR) protein expression in the prefrontal cortex (PFC) and hippocampus of LPS-treated rats. These findings suggest that ginsenoside Rg1 has protective effect against LPS-induced cognitive deficit and that prevention of LPS-induced changes in cholinergic system is crucial to this ameliorating effect.
Jiang, Xia; Jia, Lin-Wei; Li, Xiao-Hong; Cheng, Xiang-Shu; Xie, Jia-Zhao; Ma, Zhi-Wei; Xu, Wei-Jie; Liu, Yue; Yao, Yun; Du, Lai-Ling; Zhou, Xin-Wen
Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.
Full Text Available 7,8-Dihydroxyflavone (7,8-DHF, a tyrosine kinase B (TrkB agonist that mimics the neuroprotective properties of brain-derived neurotrophic factor, which can not efficiently deliver into the brain, has been reported to be useful in ameliorating cognitive impairment in many diseases. Researches have indicated that apolipoprotein E-knockout (ApoE-KO mouse was associated with cognitive alteration via various mechanisms. Our present study investigated the possible mechanisms of cognitive impairment of ApoE-KO mouse fed with western type diet and the protective effects of 7,8-DHF in improving spatial learning and memory in ApoE-KO mouse. 5-weeks-old ApoE-KO mice and C57BL/6 mice were chronically treated with 7,8-DHF (with a dosage of 5mg/kg or vehicles orally for 25 weeks, and then subjected to Morris water maze at the age of 30 weeks to evaluate the cognitive performances. Afterwards, histology analysis and western blotting were performed. Spatial learning and memory deficits were observed in ApoE-KO mice, which were consistent with higher expression of active-asparaginyl endopeptidase (active-AEP as well as AEP-derived truncated tauN368 compared with normal group. In addition to that, long-term treatment of 7,8-DHF dramatically ameliorated cognitive decline in ApoE-KO mice, accompanied by the activation in phosphorylated protein kinase B (Akt/glycogen synthase kinase-3β (GSK-3β pathway and down-regulated expression of tau S396 and PHF-tau (phosphorylated tau at ser396 and ser404 epitope. These findings suggested that cognitive impairment of ApoE-KO mouse might associate with tau pathology and 7,8-DHF could activate AKT and then phosphorylate its downstream molecule to inhibit expression of abnormal tau, meanwhile, 7,8-DHF could reduce the expression of active-AEP and then inhibit production of truncated tauN368.
Tawfik, Mona K
Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.
Lee, Jae-Min; Park, Jong-Min; Song, Min Kyung; Oh, Yoo Joung; Kim, Chang-Ju; Kim, Youn-Jung
Vascular dementia is the progressive change in blood vessels that leads to neuronal injuries in vulnerable areas induced by chronic cerebral hypoperfusion (CCH). CCH induces disruption of blood-brain barrier (BBB), and this BBB disruption can initiate the cognitive impairment and white matter injury. In the present study, we evaluated the effect of treadmill exercise on the cognitive impairment, white matter injury, and BBB disruption induced by CCH. Vascular dementia was induced by permanent bilateral common carotid arteries occlusion (BCCAO) in rats. The rats in the exercise group were made to run on a treadmill for 30min once a day for 14 weeks, starting 4 weeks after birth. Our results revealed that treadmill exercise group was alleviated the cognitive impairment and myelin degradation induced by CCH. The disruption of BBB after CCH indicates degradation of occludin, zonula occluden-1 (ZO-1), and up-regulation of matrix metalloproteinases (MMPs). Treadmill exercise may provide protective effects on BBB disruption from degradation of occludin, ZO-1, and overexpression of MMP-9 after CCH. These findings suggest that treadmill exercise ameliorates cognitive impairment and white matter injury from BBB disruption induced by CCH in rats. The present study will be valuable for means of prophylactic and therapeutic intervention for patients with CCH.
Luo, Pan; Zhang, Xiaoxue; Lu, Yun; Chen, Cheng; Li, Changjun; Zhou, Mei; Lu, Qing; Xu, Xulin; Shen, Guanxin; Guo, Lianjun
Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Two weeks later, rats were treated with 30 mg/kg fluoxetine (intragastric injection, i.g.) for 6 weeks. Cognitive function was evaluated by Morris water maze (MWM) and novel objects recognition (NOR) test. Long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Western blotting was used to quantify the protein levels. Our results showed that fluoxetine treatment significantly improved the cognitive impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, 2VO caused an up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) surface expressions in the hippocampal CA1 area and fluoxetine also effectively recovered the disorder of HCN2 surface expressions, which may be a possible mechanism that fluoxetine treatment ameliorates cognitive impairments in rats with CCH.
Zhang, Lei; Zhang, Hu-Qin; Liang, Xiang-Yan; Zhang, Hai-Feng; Zhang, Ting; Liu, Fang-E
Sleep deprivation (SD) has been shown to induce oxidative stress which causes cognitive impairment. Melatonin, an endogenous potent antioxidant, protects neurons from oxidative stress in many disease models. The present study investigated the effect of melatonin against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. SD was induced in rats using modified multiple platform model. Melatonin (15 mg/kg) was administered to the rats via intraperitoneal injection. The open field test and Morris water maze were used to evaluate cognitive ability. The cerebral cortex (CC) and hippocampus were dissected and homogenized. Nitric oxide (NO) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) enzyme activity of hippocampal and cortical tissues (10% wet weight per volume) were performed to determine the level of oxidative stress. The expression of brain-derived neurotrophic factor (BDNF) and calcium-calmodulin dependent kinase II (CaMKII) proteins in CC and hippocampus was assayed by means of immunohistochemistry. The results revealed that SD impairs cognitive ability, while melatonin treatment prevented these changes. In addition, melatonin reversed SD-induced changes in NO, MDA and SOD in both of the CC and hippocampus. The results of immunoreactivity showed that SD decreased gray values of BDNF and CaMKII in CC and hippocamal CA1, CA3 and dentate gyrus regions, whereas melatonin improved the gray values. In conclusion, our results suggest that melatonin prevents cognitive impairment induced by SD. The possible mechanism may be attributed to its ability to reduce oxidative stress and increase the levels of CaMKII and BDNF in CC and hippocampus.
Dichgans, Martin; Leys, Didier
Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.
Zhou, Dongsheng; Liu, Huaxia; Li, Chenli; Wang, Fangyan; Shi, Yaosheng; Liu, Lingjiang; Zhao, Xin; Liu, Aiming; Zhang, Junfang; Wang, Chuang; Chen, Zhongming
Amyloid-beta (Aβ) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3β (GSK3β) pathway and deactivates GSK3β signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learning and memory performance, reduce Aβ and phosphorylated tau levels in mouse model of Alzheimer's disease (AD). However, it still remains unclear whether atorvastatin is responsible for regulation of AKT/GSK3β signaling and contributes to subsequent down-regulation of Aβ1-42 and phosphorylated tau in APP/PS1 transgenic (Tg APP/PS1) mice. Herein, we aimed to investigate the possible impacts of atorvastatin (10 mg/kg, p.o.) on the memory deficit by behavioral tests and changes of AKT/GSK3β signaling in hippocampus and prefrontal cortex by western blot test in Tg APP/PS1 mice. The results showed that treatment with atorvastatin significantly reversed the memory deficit in the Tg APP/PS1 mice in a novel object recognition and the Morris water maze tests. Moreover, atorvastatin significantly attenuated Aβ1-42 accumulation and phosphorylation of tau (Ser396) in the hippocampus and prefrontal cortex of Tg APP/PS1 mice. In addition, atorvastatin treatment also increased phosphorylation of AKT, inhibited GSK3β activity by increasing phosphorylation of GSK3β (Ser9) and decreasing the beta-site APP cleaving enzyme 1 (BACE1) expression. These results indicated that the memory ameliorating effect of atorvastatin may be, in part, by regulation the AKT/GSK3β signaling which may contribute to down-regulation of Aβ1-42 and tau hyperphosphorylation.
Rubovitch, Vardit; Zilberstein, Yael; Chapman, Joab; Schreiber, Shaul; Pick, Chaim G.
Blast induced traumatic brain injury (B-TBI) may cause various degrees of cognitive and behavioral disturbances but the exact brain pathophysiology involved is poorly understood. It was previously suggested that ganglioside alteration on the axon surface as well as axonal regenerating inhibitors (ARIs) such as myelin associated glycoprotein (MAG) were involved in axonal outgrowth inhibition (AOI), leading to brain damage. GM1 ganglioside content in the brain was significantly reduced while GD1 ganglioside was not affected. The axonal regeneration was also reduced as seen by the phosphorylated NF-H expression. Moreover, B-TBI induced a significant elevation in MAG expression in the brains of the injured mice. The blast injured mice exhibited a significant decline in spatial memory as seen by the Y-maze test. In addition, the injured mice showed pronounced damage to the visual memory (as evaluated by the Novel object recognition test). A single low dose of GM1 (2 mg/kg; IP), shortly after the injury, prevented both the cognitive and the cellular changes in the brains of the injured mice. These results enlighten part of the complicated mechanism that underlies the damage induced by B-TBI and may also suggest a potential new treatment strategy for brain injuries. PMID:28112258
Arteaga, Olatz; Revuelta, M; Urigüen, L; Martínez-Millán, L; Hilario, E; Álvarez, A
As the interest in the neuroprotective possibilities of docosahexaenoic acid (DHA) for brain injury has grown in the recent years, we aimed to investigate the long-term effects of this fatty acid in an experimental model of perinatal hypoxia-ischemia in rats. To this end, motor activity, aspects of learning, and memory function and anxiety, as well as corticofugal connections visualized by using tracer injections, were evaluated at adulthood. We found that in the hours immediately following the insult, DHA maintained mitochondrial inner membrane integrity and transmembrane potential, as well as the integrity of synaptic processes. Seven days later, morphological damage at the level of the middle hippocampus was reduced, since neurons and myelin were preserved and the astroglial reactive response and microglial activation were seen to be diminished. At adulthood, the behavioral tests revealed that treated animals presented better long-term working memory and less anxiety than non-treated hypoxic-ischemic animals, while no difference was found in the spontaneous locomotor activity. Interestingly, hypoxic-ischemic injury caused alterations in the anterograde corticofugal neuronal connections which were not so evident in rats treated with DHA. Thus, our results indicate that DHA treatment can lead to long-lasting neuroprotective effects in this experimental model of neonatal hypoxia-ischemic brain injury, not only by mitigating axonal changes but also by enhancing cognitive performance at adulthood.
... stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It can involve problems with memory, language, thinking and judgment that are greater than normal age-related changes. If you have mild cognitive impairment, you may ...
Lance A. Johnson
Full Text Available Obesity, metabolic syndrome (MetS and type 2 diabetes (T2D are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D, multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV, a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.
Johnson, Lance A; Zuloaga, Kristen L; Kugelman, Tara L; Mader, Kevin S; Morré, Jeff T; Zuloaga, Damian G; Weber, Sydney; Marzulla, Tessa; Mulford, Amelia; Button, Dana; Lindner, Jonathan R; Alkayed, Nabil J; Stevens, Jan F; Raber, Jacob
Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.
α₄β₂ Nicotinic receptor stimulation of the GABAergic system within the orbitofrontal cortex ameliorates the severe crossmodal object recognition impairment in ketamine-treated rats: implications for cognitive dysfunction in schizophrenia.
Cloke, Jacob M; Winters, Boyer D
Schizophrenia is associated with atypical multisensory integration. Rats treated sub-chronically with NMDA receptor antagonists to model schizophrenia are severely impaired on a tactile-to-visual crossmodal object recognition (CMOR) task, and this deficit is reversed by systemic nicotine. The current study assessed the receptor specificity of the ameliorative effect of nicotine in the CMOR task, as well as the potential for nicotinic receptor (nAChR) interactions with GABA and glutamate. Male Long-Evans rats were treated sub-chronically for 10 days with ketamine or saline and then tested on the CMOR task after a 10-day washout. Systemic nicotine given before the sample phase of the CMOR task reversed the ketamine-induced impairment, but this effect was blocked by co-administration of the GABAA receptor antagonist bicuculline at a dosage that itself did not cause impairment. Pre-sample systemic co-administration of the NMDA receptor antagonist MK-801 did not block the remediating effect of nicotine in ketamine-treated rats. The selective α7 nAChR agonist GTS-21 and α4β2 nAChR agonist ABT-418 were also tested, with only the latter reversing the ketamine impairment dose-dependently; bicuculline also blocked this effect. Similarly, infusions of nicotine or ABT-418 into the orbitofrontal cortex (OFC) reversed the CMOR impairment in ketamine-treated rats, and systemic bicuculline blocked the effect of intra-OFC ABT-418. These results suggest that nicotine-induced agonism of α4β2 nAChRs within the OFC ameliorates CMOR deficits in ketamine-treated rats via stimulation of the GABAergic system. The findings of this research may have important implications for understanding the nature and potential treatment of cognitive impairment in schizophrenia.
Acharya, Munjal M; Martirosian, Vahan; Christie, Lori-Ann; Riparip, Lara; Strnadel, Jan; Parihar, Vipan K; Limoli, Charles L
Past preclinical studies have demonstrated the capability of using human stem cell transplantation in the irradiated brain to ameliorate radiation-induced cognitive dysfunction. Intrahippocampal transplantation of human embryonic stem cells and human neural stem cells (hNSCs) was found to functionally restore cognition in rats 1 and 4 months after cranial irradiation. To optimize the potential therapeutic benefits of human stem cell transplantation, we have further defined optimal transplantation windows for maximizing cognitive benefits after irradiation and used induced pluripotent stem cell-derived hNSCs (iPSC-hNSCs) that may eventually help minimize graft rejection in the host brain. For these studies, animals given an acute head-only dose of 10 Gy were grafted with iPSC-hNSCs at 2 days, 2 weeks, or 4 weeks following irradiation. Animals receiving stem cell grafts showed improved hippocampal spatial memory and contextual fear-conditioning performance compared with irradiated sham-surgery controls when analyzed 1 month after transplantation surgery. Importantly, superior performance was evident when stem cell grafting was delayed by 4 weeks following irradiation compared with animals grafted at earlier times. Analysis of the 4-week cohort showed that the surviving grafted cells migrated throughout the CA1 and CA3 subfields of the host hippocampus and differentiated into neuronal (∼39%) and astroglial (∼14%) subtypes. Furthermore, radiation-induced inflammation was significantly attenuated across multiple hippocampal subfields in animals receiving iPSC-hNSCs at 4 weeks after irradiation. These studies expand our prior findings to demonstrate that protracted stem cell grafting provides improved cognitive benefits following irradiation that are associated with reduced neuroinflammation.
Pavlović Dragan M.
Full Text Available Mild cognitive impairment (MCI is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer's disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.
Ji, Li-Li; Peng, Jun-Bo; Fu, Chang-Hai; Cao, Dong; Li, Dan; Tong, Lei; Wang, Zhen-Yu
Among learning and memory processes, fear memories are crucial in some psychiatric disorders like post-traumatic stress disorder (PTSD). Accumulating evidence shows that the sigma-1 receptor (Sig-1R) has comprehensive involvement in cognitive impairment and neuroprotective effects. It has also been reported that BDNF appears to enhance extinction of fear in anxiety disorders via the MAPK signaling cascade. However, it remains unclear whether BDNF-TrkB-MAPK pathway may be mechanistically involved in the therapeutic effect of sigma-1 receptor in the development of PTSD. To address this question, rats were subjected to a classical single-prolonged stress procedure (SPS) and kept undisturbed for 7 days. After that, rats were re-stressed by re-exposure to the forced swim component of SPS (RSPS). Behavior tests were subsequently performed to assess anxiety and cognitive impairments. Furthermore, we analyzed the expression of BDNF and the phosphorylation of TrkB and three MAPK pathways, namely, the ERK, JNK and p38. We found that the levels of BDNF and p-TrkB were increased following the RSPS procedure, which were reversed by the administration of PRE-084. Meanwhile, among the three MAPK signaling pathways, only the p-ERK expression was increased following the RSPS procedure. Collectively, our results indicate that BDNF-TrkB-ERK signaling pathway may be involved in the activation of sigma-1 receptor to yield therapeutic benefits for PTSD.
Zhao, Xu; Liu, Chunmei; Xu, Mengjie; Li, Xiaolong; Bi, Kaishun; Jia, Ying
Lignan compounds extracted from Schisandra chinensis (Turcz.) Baill. have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease. This study was designed to investigate the effects of total lignans of Schisandra chinensis (TLS) on cognitive function and neurodegeneration in the model of AD induced by Aβ1-42 in vivo and in vitro. It was found that intragastric infusion with TLS (50 and 200 mg/kg) to Aβ1-42-induced mice significantly increased the number of avoidances in the shuttle-box test and swimming time in the target quadrant in the Morris water maze test. TLS at dose of 200 mg/kg significantly restored the activities of total antioxidant capacity (T-AOC), as well as the level of malondialdehyde (MDA) both in the hippocampus and cerebral cortex in mice. Results of histopathological examination indicated that TLS noticeably ameliorated the neurodegeneration in the hippocampus in mice. On the other hand, TLS (100 μM) could protect the Aβ1-42-induced primary mouse neuronal cells by blocking the decrease of mitochondrial membrane potential (MMP), change the expressions of Bcl-2 (important regulator in the mitochondria apoptosis pathway). Moreover, TLS also decreased the activity of β-secretase 1 (BACE1), crucial protease contributes to the hydrolysis of amyloid precursor protein (APP), and inhibited the expression of JKN/p38, which involved in the MAPKs signaling pathways in both mice and primary mouse neuronal cells. In summary, TLS might protect against cognitive deficits and neurodegeneration by releasing the damage of oxidative stress, inhibiting the expression of BACE1 and the MAPKs inflammatory signaling pathways.
Full Text Available Lignan compounds extracted from Schisandra chinensis (Turcz. Baill. have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease. This study was designed to investigate the effects of total lignans of Schisandra chinensis (TLS on cognitive function and neurodegeneration in the model of AD induced by Aβ1-42 in vivo and in vitro. It was found that intragastric infusion with TLS (50 and 200 mg/kg to Aβ1-42-induced mice significantly increased the number of avoidances in the shuttle-box test and swimming time in the target quadrant in the Morris water maze test. TLS at dose of 200 mg/kg significantly restored the activities of total antioxidant capacity (T-AOC, as well as the level of malondialdehyde (MDA both in the hippocampus and cerebral cortex in mice. Results of histopathological examination indicated that TLS noticeably ameliorated the neurodegeneration in the hippocampus in mice. On the other hand, TLS (100 μM could protect the Aβ1-42-induced primary mouse neuronal cells by blocking the decrease of mitochondrial membrane potential (MMP, change the expressions of Bcl-2 (important regulator in the mitochondria apoptosis pathway. Moreover, TLS also decreased the activity of β-secretase 1 (BACE1, crucial protease contributes to the hydrolysis of amyloid precursor protein (APP, and inhibited the expression of JKN/p38, which involved in the MAPKs signaling pathways in both mice and primary mouse neuronal cells. In summary, TLS might protect against cognitive deficits and neurodegeneration by releasing the damage of oxidative stress, inhibiting the expression of BACE1 and the MAPKs inflammatory signaling pathways.
Li, J; Ding, X; Zhang, R; Jiang, W; Sun, X; Xia, Z; Wang, X; Wu, E; Zhang, Y; Hu, Y
So far, no effective disease-modifying therapies for Alzheimer's disease (AD) aiming at protecting or reversing neurodegeneration of the disease have been established yet. The present work aims to elucidate the effect of Harpagoside (abbreviated HAR), an iridoid glycosides purified from the Chinese medicinal herb Scrophularia ningpoensis, on neurodegeneration induced by β-amyloid peptide (Aβ) and the underlying molecular mechanism. Here we show that HAR exerts neuroprotective effects against Aβ neurotoxicity. Rats injected aggregated Aβ₁₋₄₀ into the bilateral hippocampus displayed impaired spatial learning and memory ability in a Y-maze test and novel object recognition test, while HAR treatment ameliorated Aβ₁₋₄₀-induced behavioral deficits. Moreover, administration of HAR increased the expression levels of brain-derived neurotrophic factor (BDNF) and activated the extracellular-regulated protein kinase (ERK) and the phosphatidylinositol 3-kinase (PI3-kinase) pathways both in the cerebral cortex and hippocampus of the Aβ₁₋₄₀-insulted rat model. Furthermore, in cultured primary cortical neurons, Aβ₁₋₄₂ induced significant decrease of choline acetyltransferase (ChAT)-positive neuron number and neurite outgrowth length, both of which were dose dependently increased by HAR. In addition, HAR pretreatment also significantly attenuated the decrease of cell viability in Aβ₁₋₄₂-injured primary cortical neurons. Finally, when K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody were added to the culture medium 2 h prior to HAR addition, the protective effect of HAR on Aβ₁₋₄₂-induced neurodegeneration in the primary cortical neuron was almost inhibited. Taken together, HAR exerting neuroprotection effect and ameliorating learning and memory deficit appears to be associated, at least in part, with up-regulation of BDNF content as well as activating its downstream signaling pathways, e.g., MAPK
Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Towards the therapeutics of cognitive impairment of schizophrenia
Full Text Available Rationale Augmentation therapy with serotonin-1A (5-HT1A receptor partial agonists has been suggested to improve cognitive deficits in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production.Objectives and methods The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days of tandospirone (0.05 and 5 mg/kg on brain energy metabolism, as represented by extracellular lactate concentration (eLAC in the medial prefrontal cortex (mPFC of young adult rats..Results Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot shock stress (FS. Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment.Conclusions These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism based on brain energy metabolism by which 5-HT1A agonism improve cognitive impairment in schizophrenia and related disorders.
Xiong, Li; Reijmer, Yael D; Charidimou, Andreas; Cordonnier, Charlotte; Viswanathan, Anand
Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic and hemorrhagic. However the contribution of spontaneous intracerebral hemorrhage presumed due to small vessel diseases on cognitive impairment is underestimated, in contrast to the numerous studies about the role of ischemic vascular disorders on cognition. In this review we summarize recent findings from clinical studies and appropriate basic science research to better elucidate the role and possible mechanisms of intracerebral hemorrhage in cognitive impairment and dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T
People with cognitive disabilities are gaining in a long struggle for recognition of their right to control their lives. In the information society access to the Web is essential to this control. Cognitive barriers to this access are diverse, reflecting the complexity of human cognitive faculties. These barriers are not well managed in current accessibility practice and policy, in part because cognitive accessibility, like usability, cannot be reduced to a checklist of simple attributes. Advances in representing the meaning as well as the form of information, and in supporting configurable presentation and interaction methods, will yield progress. Increased inclusion of people with cognitive disabilities in the processes of technology development and policy making will also pay off.
Yang, Yang; Tang, Bei-Sha; Guo, Ji-Feng
Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice.
Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice. PMID:28058128
Saedi, Elham; Gheini, Mohammad Reza; Faiz, Firoozeh; Arami, Mohammad Ali
There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings. PMID:27660698
Hua Zhou; Zhong Zhao
Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.
Sun, Jun-Jun; Ren, Qing-Guo; Xu, Lin; Zhang, Zhi-Jun
More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients.
Currently, there are no effective pharmaceutical treatments to reduce cognitive decline or prevent dementia. At the same time, the global population is aging, and rates of dementia and mild cognitive impairment (MCI) are on the rise. As such, there is an increasing interest in complementary and alternative interventions to treat or reduce the risk of cognitive decline. Depression is one potentially modifiable risk factor for cognitive decline and dementia. Notably, exercise and yoga are two interventions known to both reduce symptoms of depression and improve cognitive function. The current review discusses the efficacy of exercise and yoga to ameliorate depression and thereby reduce the risk of cognitive decline and potentially prevent dementia. Potential mechanisms of change, treatment implications, and future directions are discussed. PMID:28044084
Full Text Available Cognitive impairment (CI is increasingly recognized as a common adverse consequence of heart failure (HF. Although the exact mechanisms remain unclear, microembolism, chronic or intermittent cerebral hypoperfusion, and/or impaired cerebral vessel reactivity that lead to cerebral hypoxia and ischemic brain damage seem to underlie the development of CI in HF. Cognitive decline in HF is characterized by deficits in one or more cognition domains, including attention, memory, executive function, and psychomotor speed. These deficits may affect patients’ decision-making capacity and interfere with their ability to comply with treatment requirements, recognize and self-manage disease worsening symptoms. CI may have fluctuations in severity over time, improve with effective HF treatment or progress to dementia. CI is independently associated with disability, mortality, and decreased quality of life of HF patients. It is essential therefore for health professionals in their routine evaluations of HF patients to become familiar with assessment of cognitive performance using standardized screening instruments. Future studies should focus on elucidating the mechanisms that underlie CI in HF and establishing preventive strategies and treatment approaches.
Norberto Anizio Ferreira Frota
Full Text Available Abstract Wilson's disease (WD or hepatolenticular degeneration is a rare, genetic and systemic disease, caused by a deficit in the metabolism of copper, leading to its accumulation in different organs, mainly the liver, followed by the central nervous system, especially the basal ganglia. When symptoms begin between the second and third decades of life, approximately 50% of the patients show neurological symptoms. Although dystonia and dysarthria are the most common neurological signs, cognitive changes have been reported since the first cases were described in 1912. Memory change is one of the most common impairments, but other cognitive changes have been reported, including dementia in untreated cases. In this article we review the cognitive changes in WD patients and the occurrence of dementia.
Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.
Andersen, Kjeld; Nybo, Hanne; Gaist, David;
the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24-30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18-23 points, and severe impairment was defined as a score of 0-17 points. Cox...... regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence...
Full Text Available The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.
Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy.
Natalia Vasilyevna Vakhnina
Full Text Available Cognitive impairments (CIs are a highly common type of neurological disorders particularly in elderly patients. Choice of a therapeutic strategy for CI is determined by the etiology of abnormalities and their degree. Measures to prevent CI progression and dementia: adequate treatment of existing cardiovascular diseases, prevention of stroke, balanced nutrition, moderate physical and intellectual exercises, and combatting overweight and low activity are of basic value in treating mild and moderate CIs. According to the data of a number of investigations, the above measures reduce the risk of dementia, including in the genetically predisposed. Pharmacotherapy for mild and moderate CIs generally comprises vasoactive, neurometabolic, and noradrenergic agents. The indication for the use of memantine and/or acetylcholinergic agents, i.e. basic therapy for the most common forms of dementia (Alzheimer's disease, Lewy body dementia, vascular, and mixed dementia, hepatic colics is severe CIs. The long-term use of memantine and/or acetylcholinergic agents alleviates the cognitive and behavioral symptoms of dementia, enhances self-dependence in patients, and prolongs their active lifetime.
Magnuson, Allison; Mohile, Supriya; Janelsins, Michelle
Aging is a risk factor for cognitive impairment as well as cancer. However, the interplay between these three entities - aging, cognition and cancer - is not well understood. Mounting evidence indicates that both cancer and cancer therapies, such as chemotherapy, can negatively affect cognition and that older adults with pre-existing cognitive impairment may be more susceptible to cognitive decline with therapy than younger patients. For an older adult, decline in cognition may significantly compromise their ability to remain independent in the community. Pre-existing cognitive impairment, at the time of a cancer diagnosis, may also carry an increased risk of treatment-related adverse events in older adults receiving chemotherapy. Growing research suggests behavioral interventions may be helpful in improving chemotherapy-related cognitive changes; however, these interventions have been mainly evaluated in younger patients in whom pre-existing cognitive impairment is less prevalent. Here we review the studies on: cognitive changes associated with cancer and cancer therapies with an emphasis on studies conducted in older adults, relevant screening tools to evaluate cognition in the geriatric oncology setting, and possible intervention strategies for managing cognitive impairment.
Hota, Sunil Kumar; Barhwal, Kalpana; Baitharu, Iswar; Prasad, Dipti; Singh, Shashi Bala; Ilavazhagan, Govindasamy
Hypobaric hypoxia induced memory impairment has been attributed to several factors including increased oxidative stress, depleted mitochondrial bioenergetics, altered neurotransmission and apoptosis. This multifactorial response of the brain to hypobaric hypoxia limits the use of therapeutic agents that target individual pathways for ameliorating hypobaric hypoxia induced memory impairment. The present study aimed at exploring the therapeutic potential of a bacoside rich leaf extract of Bacopa monniera in improving the memory functions in hypobaric conditions. The learning ability was evaluated in male Sprague Dawley rats along with memory retrieval following exposure to hypobaric conditions simulating an altitude of 25,000 ft for different durations. The effect of bacoside administration on apoptosis, cytochrome c oxidase activity, ATP levels, and oxidative stress markers and on plasma corticosterone levels was investigated. Expression of NR1 subunit of N-methyl-d-aspartate receptors, neuronal cell adhesion molecules and was also studied along with CREB phosphorylation to elucidate the molecular mechanisms of bacoside action. Bacoside administration was seen to enhance learning ability in rats along with augmentation in memory retrieval and prevention of dendritic atrophy following hypoxic exposure. In addition, it decreased oxidative stress, plasma corticosterone levels and neuronal degeneration. Bacoside administration also increased cytochrome c oxidase activity along with a concomitant increase in ATP levels. Hence, administration of bacosides could be a useful therapeutic strategy in ameliorating hypobaric hypoxia induced cognitive dysfunctions and other related neurological disorders.
Sun, Li; Xie, Keliang; Zhang, Changsheng; Song, Rui; Zhang, Hong
Cognitive decline after surgery in the elderly population is a major clinical problem with high morbidity. Hyperbaric oxygen (HBO) preconditioning can induce significant neuroprotection against acute neurological injury. We hypothesized that HBO preconditioning would prevent the development of postoperative cognitive impairment. Elderly male rats (20 months old) underwent stabilized tibial fracture operation under general anesthesia after HBO preconditioning (once a day for 5 days). Separate cohorts of animals were tested for cognitive function with fear conditioning and Y-maze tests, or euthanized at different times to assess the blood-brain barrier integrity, systemic and hippocampal proinflammatory cytokines, and caspase-3 activity. Animals exhibited significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after surgery, which were significantly prevented by HBO preconditioning. Furthermore, HBO preconditioning significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1 β (IL-1β), IL-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, HBO preconditioning markedly improved blood-brain barrier integrity and caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that HBO preconditioning could significantly mitigate surgery-induced cognitive impairment, which is strongly associated with the reduction of systemic and hippocampal proinflammatory cytokines and caspase-3 activity.
Leonard A. Jason
Full Text Available Chronic fatigue syndrome (CFS is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994. Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS, is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009. Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment. A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.
Full Text Available Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD and a major influencing factor on patients' daily living ability. Mild cognitive impairment (MCI is a cognitive state between normal aging and dementia, and the living capability of MCI patients relatively remains. MCI often occurs in PD, with its clinical features presenting as the impairment in working memory and (or attention, executive function, language ability, memory and visuospatial function. Here we try to depict the general picture of PD-MCI from the view of epidemiology, pathology, clinical presentation, imaging and diagnostic criteria.
differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen.
Full Text Available Aim: to identify the degree of cognitive impairment (CN and to optimize the treatment of patients with multiple sclerosis (MS. Material and methods. A total of 695 patients (278 men and 417 women were ranged from 18 to 63 years. The mean age was 30.2±0.7 years: women (417 28.5±0.5 years, while for men (278 31.8±0.7 years. Relaps-ing-remitting type (RT of MS was established in 520 patients (74.8%, secondary progressive type (VPT MS in 132 patients (18.9% and primary progressive type (PPT MS in 10 patients (1.5%. Clinically isolated syndrome (CIS was detected in 33 patients (4.8%. The diagnosis of MS 662 patients according to the criteria McDonald etal. (2005. Score of neurologic deficit was carried out on an extended scale of disability (Expanded Disability Status Scale — EDSS. CN were evaluated by conventional tests. To estimate the orientation in time, assessment of short-term and long-term memory, attention and concentration, as well as executive functions, memory, language, evaluation of optical-spatial activities, conceptual thinking, the account used by the Montreal Cognitive Assessment Scale (MoCA. For the screening of dementia with a primary lesion of the frontal lobes and subcortical cerebral structures used battery frontal test to assess frontal dysfunction. Results. The ratio of male (265 and female (397 was 1:1.5. The severity of the condition patients EDSS scale ranged from 1.5 to 8.0 points, and the average score was 3.5±1.2. In the group of patients with RT RS average score EDSS was more than a half (2.5±1.1, than in the group of patients with MS VAC (5.5±1.2 and POS PC (6.5±1.2. In the study of history, it was found that the development of the RS (662 patients was preceded by the following conditions: a viral infection in 277 patients (41.84%; fatigue in 147 patients (22.21%; transferred psycho-emotional load from 218 (32.93%; after pregnancy and childbirth in 20 patients (3.02%. Conclusion. Among the patients with MS
Daradkeh, Ghazi; Essa, Musthafa M; Al-Adawi, S Samir; Koshy, Roopa P; Al-Asmi, Abdullah; Waly, Mostafa I
The elderly population is increasing worldwide and it has been suggested that senior citizens will continue to constitute the bulk of the population in many countries. Nutritional status of senior citizens are adversely affected by their frailty, chronic condition and declining cognitive functioning. Conversely, malnourished elderly further deteriorate their frailty, chronic disease and cognitive functioning. The aim of this review article is to recognize the importance of nutritional assessment of elderly population particularly those with cognitive impairment. First part is to highlight characteristic cognitive impairment among senior citizens and the second one highlight t he background in which malnutrition is a factor that leads to increased risk of morbidity and mortality in the elderly. This review also highlight salgorithms for safeguarding nutritional status among senior citizen and focuses on importance of nutritional screening, assessment and early intervention for safeguarding further deterioration of elderly who are likely to prone to cognitive impairment.
Rao, Mukund G; Holla, Bharath; Varambally, Shivarama; Raveendranathan, Dhanya; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N
Piracetam is a cognitive-enhancing agent that is used for the treatment of cognitive impairments of various etiologies. Little is known about its side effect profile, especially in those with psychiatric illness. We herewith present two cases with cognitive impairment who had contrasting responses to piracetam. One of them with organic amnestic syndrome had significant improvement, whereas the other who had an organic personality change as well as a family history of mental illness had significant worsening of behavioral problems after piracetam was introduced. This report highlights the need for caution in the use of piracetam, especially in those with past or family history of psychiatric illness.
Full Text Available Abstract Background We assessed preferences for current health using the visual analogue scale (VAS, standard gamble (SG, time trade-off (TTO, and willingness to pay (WTP in patients with cerebral aneurysms, a population vulnerable to cognitive deficits related to aneurysm bleeding or treatment. Methods We measured VAS, SG, TTO, and WTP values for current health in 165 outpatients with cerebral aneurysms. We assessed cognitive impairment with the Mini Mental State Examination (MMSE; scores Results Eleven patients (7% had MMSE scores Conclusion Cognitive impairment is associated with lower preferences for current health in patients with cerebral aneurysms. Cognitively impaired patients have poor inter-preference test correlations and different response distributions compared to unimpaired patients.
de Haan, Edward H.; Nys, Gudrun M.; Van Zandvoort, Martine J.
Purpose of review This review of the cognitive status following stroke and vascular cognitive impairment starts by questioning the concept of vascular dementia and related concepts. Our position is that in many cases these labels promote a superficial conceptualization of an inherently complex and h
Olsen, Kirsty; Taylor, John-Paul; Thomas, Alan
Driving is an important aspect of daily living and for many older people provides autonomy and psycho-social benefits. Cognitive impairment has been found to impact driving skills at the level of dementia, however, uncertainty remains around the impact of a diagnosis of the pre-dementia condition mild cognitive impairment. Current official guidelines are unclear, and assessment of fitness to drive can be problematical. This editorial examines current official guidance available to the clinician and problems with existing assessment as well as the current position of research specifically into MCI and driving, and considers future direction for research in this field.
Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS, a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT, Poria cum Radix Pini (PRP and Radix Polygalae (RP, is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease.
Laura Leto; Mauro Feola
Cognitive damage in heart failure (HF) involves different domains thus interfering with the ability for single patient to self-care and to cope with treatment regimens, modifying symptoms and health behaviours. Many cerebral and functional changes were detected in brain imaging, involving areas of both grey and white matter deputed to cognition. Although various instruments are available to explore cognition, no consensus was obtained on better tools to be used in HF population. Reduction in cerebral blood flow, decreased cardiac output, altera-tions of cerebrovascular reactivity and modification of blood pressure levels are the main features involved in the etiopathogenetic mecha-nisms of cognitive deficit. Several cardiac variables, laboratory parameters, demographic and clinical elements were studied for their possible relation with cognition and should be properly evaluated to define patients at increased risk of impairment. The present review gathers avail-able data pointing out assured information and discussing possible areas of research development.
Full Text Available The purpose of the study was to identify changes in cognitive abilities that affect patients with relapsing remitting form of multiple sclerosis (MS and to find out which instrument manifests them best. The performance of MS patients was compared to a matched group of healthy people using three neuropsychological tests: Wisconsin card sorting test (WCST, Stroop color and word test and Trail making test (TMT part B. Results on all three tests indicate general cognitive impairments in the group of patients. Compared to the group of healthy people patients with MS exhibited impaired ability of abstract reasoning (WCST, impaired cognitive flexibility and less resistance to irrelevant stimuli (Stroop color and word test, slowed information processing and impaired ability of shifting attention from one symbol to another (TMT. The largest differences between groups occured in Stroop color and word test as well as in TMT. The estimation of cognitive abilities of MS patients is of high importance and sistematicaly observing of changes in those abilities should be considered.
Rooij, F.G. van; Schaapsmeerders, P.; Maaijwee, N.A.; Duijnhoven, D.A. van; Leeuw, F.E. de; Kessels, R.P.; Dijk, E.J. van
BACKGROUND AND PURPOSE: By definition, the symptoms of a transient ischemic attack (TIA) subside completely within 24 hours. Imaging studies show signs of persistent ischemic tissue damage in a substantial amount of patients with TIA. Cerebral infarction can cause permanent cognitive impairment. Whe
Rooij, F.G. van; Schaapsmeerders, P.; Maaijwee, N.A.M.M.; Duijnhoven, D.A. van; de Leeuw, F.E.; Kessels, R.P.C.; Dijk, E.J. van
Background and Purpose—By definition, the symptoms of a transient ischemic attack (TIA) subside completely within 24 hours. Imaging studies show signs of persistent ischemic tissue damage in a substantial amount of patients with TIA. Cerebral infarction can cause permanent cognitive impairment. Whet
Full Text Available Cognitive dysfunction is common non-motor symptom (NMS in Parkinson's disease (PD, which affects the patients' quality of life and increases the burden of caregivers. Cognitive dysfunction in PD can be mild cognitive impairment (MCI or dementia. MCI presents in the early stage of PD and the incidence rate is increasing with the disease progression. In some cases it can advance to dementia. The diagnosis of MCI in PD includes inclusion criteria, exclusion criteria and damage level evaluation. Non-pharmacological therapy, such as exercise and cognitive behavior therapy (CBT can improve the symptoms of MCI in PD, while the pharmacological treatment remains to be further studied. DOI: 10.3969/j.issn.1672-6731.2016.06.002
Objective To investigate metabolite changes in the brain of patients with non-dementia vascular cognitive impairment(VCIND) and mild cognitive impairment(MCI) using magnetic resonance spectroscopy(MRS)
Mason, Sarah; Craig, David; O'Neill, Sonia; Donnelly, Mark; Nugent, Chris
Demographic changes highlight the need to address disabilities associated with the costly morbidities of old age, such as dementia. Memory impairment associated with dementia represents a significant challenge for many older people. Difficulties occur in carrying out activities in their entirety or in commencing them at all. Technology has the potential to help individuals overcome the barriers created by cognitive disability in terms of performing activities of daily living and therefore help to maintain independence and enhance quality of life (Czaja, 2005). This literature review examines the current reported research, which employs electronic reminding technology to support individuals with cognitive impairment. These devices range from everyday technologies, such as phones, to sophisticated interactive devices with specifically designed software. A summary of the current evidence base is presented and recommendations for future practice are made.
Jaszke-Psonka, Magdalena; Piegza, Magdalena; Ścisło, Piotr; Pudlo, Robert; Piegza, Jacek; Badura-Brzoza, Karina; Leksowska, Aleksandra; Hese, Robert T.; Gorczyca, Piotr W.
Aim To evaluate the incidence and severity of the impairment of selected cognitive functions in patients after sudden cardiac arrest (SCA) in comparison to patients after myocardial infarction without SCA and healthy subjects and to analyze the influence of sociodemographic and clinical parameters and the duration of cardiac arrest on the presence and severity of the described disorders. Material and methods The study group comprised 30 cardiac arrest survivors, the reference group comprised ...
LIU Xin Yan; LI Li; XIAO Jia Qing; HE Chang Zhi; LYU Xiu Lin; GAO Lei; YANG Xiao Wei; CUI Xin Gang; FAN Li Hua
ObjectiveWe investigated the feasibility and efficacy of cognitive training for older adults in rural settings and with low education levels, who have mild cognitive impairment (MCI). MethodsForty-five older adults (ages >65 years) with MCI were assigned to treatment or control groups, at a 2:1 ratio. Cognitivetraining occurred in the treatment group for 2 months. The cognitive abilities of the participants were assessed at pre-training, metaphase, and post-training time points, using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), and Hamilton Depression Scale (HAM-D). ResultsFollowing training, cognitive abilities improved in the treatment group, based on the total scores of all 4 measures, as well as specifically on the MoCA and LOTCA. There were differences in the main effects of group and time point on some subscales, but these differences had little, if any, effect on the overall analyses. ConclusionThe present study demonstrated that cognitive training has beneficial effects on attention, language, orientation, visual perception, organization of visual movement, and logical questioning in patients with MCI. Furthermore, the observed effects are long-term changes.
Full Text Available Background: Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia. Methods: This is a cross-sectional study of 300 Chinese participants (age: ≥60 years from the ongoing Epidemiology of Dementia in Singapore study who underwent detailed clinical examinations including retinal photography, brain imaging and neuropsychological testing. Retinal vascular parameters were assessed from optic disc-centered photographs using a semiautomated program. A comprehensive neuropsychological battery was administered, and cognitive function was summarized as composite and domain-specific Z-scores. Cognitive impairment no dementia (CIND and dementia were diagnosed according to standard diagnostic criteria. Results: Among 268 eligible nondemented participants, 78 subjects were categorized as CIND-mild and 69 as CIND-moderate. In multivariable adjusted models, reduced retinal arteriolar and venular fractal dimensions were associated with an increased risk of CIND-mild and CIND-moderate. Reduced fractal dimensions were associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed. Conclusion: A sparser retinal microvascular network, represented by reduced arteriolar and venular fractal dimensions, was associated with cognitive impairment, suggesting that early microvascular damage may be present in preclinical stages of dementia.
Bowler, J V
Vascular dementia (VaD) is increasingly recognised to reflect an outmoded concept in that it identifies cases too late for preventive therapy to have an opportunity to prevent the development of dementia and uses a cognitive paradigm inappropriately based on Alzheimer's disease. A replacement is urgently required and a new concept, that of vascular cognitive impairment (VCI), has been proposed to meet this need. It is imperative that criteria for VCI are developed on the basis of knowledge and data rather than supposition and assumption, as was the case for VaD. This review details the state of knowledge that we have now reached concerning the fundamental points of severity and cognitive paradigm and also covers a number of other imaging-related essential points embracing atrophy, leukoaraiosis, infarct volume and infarct location. Finally, the increasingly important concept of mixed dementia (co-existent Alzheimer's disease and VCI) is discussed.
Jin Bae Weon
Full Text Available Codonopsis lanceolata (Campanulaceae have been traditionally used to treat lung inflammatory diseases, such as asthma, tonsillitis, and pharyngitis. The present study was performed to evaluate the cognitive-enhancing effects of steamed and fermented C. lanceolata in scopolamine-induced memory impairments in mice. Cognitive abilities were determined by the Morris water maze and passive avoidance tests. Mice orally received fermented C. lanceolata extract at doses of 100, 300, or 500 mg/kg body weight. Fermented C. lanceolata extract (500 mg/kg body weight, p.o. significantly shortened the escape latency times that were increased by scopolamine on the 4th day of trial sessions in the Morris water maze task. In addition, it exerted longer step-through latency times than those of the scopolamine-treated group in the passive avoidance test. Furthermore, the neuroprotective effects of fermented C. lanceolata extract on glutamate-induced neurocytotoxicity were investigated in HT22 cells. Fermented C. lanceolata extract showed a relative protection ratio of 59.62% at 500 μg/mL. In conclusion, fermented C. lanceolata extract ameliorated scopolamine-induced memory impairments, exerted neuroprotective effects, and improved activity compared to that found with original C. lanceolata. Further study will be required to investigate the mechanisms underlying this cognitive-enhancing activity.
Ren, Li; Zhang, Fan; Min, Su; Hao, Xuechao; Qin, Peipei; Zhu, Xianlin
Electroconvulsive therapy (ECT) is an effective treatment for depression, but it can induce learning and memory impairment. Our previous study found propofol (γ-aminobutyric acid (GABA) receptor agonist) could ameliorate electroconvulsive shock (ECS, an analog of ECT to animals)-induced cognitive impairment, however, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of propofol on metaplasticity and autophosphorylation of CaMKIIa in stressed rats receiving ECS. Depressive-like behavior and learning and memory function were assessed by sucrose preference test and Morris water test respectively. LTP were tested by electrophysiological experiment, the expression of CaMKIIa, p-T305-CaMKII in hippocampus and CaMKIIα in hippocampal PSD fraction were evaluated by western blot. Results suggested ECS raised the baseline fEPSP and impaired the subsequent LTP, increased the expression of p-T305-CaMKII and decreased the expression of CaMKIIα in hippocampal PSD fraction, leading to cognitive dysfunction in stressed rats. Propofol could down-regulate the baseline fEPSP and reversed the impairment of LTP partly, decreased the expression of p-T305-CaMKII and increased the expression of CaMKIIα in hippocampal PSD fraction and alleviated ECS-induced learning and memory impairment. In conclusion, propofol ameliorates ECS-induced learning and memory impairment, possibly by regulation of synaptic metaplasticity via p-T305-CaMKII.
Full Text Available Mild Cognitive Impairment (MCI causes slight but noticeable disruption in cognitive systems, primarily executive and memory functions. However, it is not clear if the development of sequence learning is affected by an impaired cognitive system and, if so, how. The goal of our study was to investigate the development of probabilistic sequence learning, from the initial acquisition to consolidation, in MCI and healthy elderly control groups. We used the Alternating Serial Reaction Time task (ASRT to measure probabilistic sequence learning. Individuals with MCI showed weaker learning performance than the healthy elderly group. However, using the reaction times only from the second half of each learning block – after the reactivation phase - we found intact learning in MCI. Based on the assumption that the first part of each learning block is related to reactivation/recall processes, we suggest that these processes are affected in MCI. The 24-hour offline period showed no effect on sequence-specific learning in either group but did on general skill learning: the healthy elderly group showed offline improvement in general reaction times while individuals with MCI did not. Our findings deepen our understanding regarding the underlying mechanisms and time course of sequence acquisition and consolidation.
Full Text Available Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%, executive disorders (89%, and social cognition impairment (78%. An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population.
the Qmci is a sensitive and specific test to differentiate between normal cognition (NC), mild cognitive impairment (MCI) and dementia. We compared the sensitivity and specificity of the subtests of the Qmci to determine which best discriminated NC, MCI and dementia.
Wallace, Meredith; Safer, Meredith
Hypersexuality, also referred to in the literature as sexually inappropriate behavior and sexual disinhibition, involves persistent, uninhibited sexual behaviors directed at oneself or at others. For older adults, the literature generally attributes the behavior to biochemical or physiological changes that accompany cognitive impairment-specifically, dementia. Although less common than other behavioral issues, such as aggression and agitation, hypersexuality presents complex logistical and ethical problems for caregivers. This article reviews the current literature on hypersexual behavior. Assessment essentials as well as nonpharmacological and pharmacological treatment approaches are discussed, identifying the need for standardization as well as caregiver education and training.
Vladimir Vladimirovich Zakharov
Full Text Available The paper gives the data of Russian and foreign authors and the results of this paper authors’ investigation of higher cerebral functions in patients who have sustained brain injury (BI. It shows their high prevalence, the predominance of cognitive impairments (CI over neurological disorders in patients with mild and moderate injury, presents their quantitative and qualitative features (a preponderance of focal symptoms in severe injury and neurodynamic disorders in mild injury, describes the predictors of their course and prognosis (the degree of injury is one of the most important predictors, and discusses current trends in the medical correction of detected abnormalities.
Full Text Available We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD. No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area was compared using the Mini Mental State Exam (MMSE, Weschler Memory Scale (WMS and the Weschler Adult Intelligent Scale (WAIS. Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. Results: Chagasic patients showed lower MMSE scores (p<004, poor orientation (p<.004, and attention (p<.007. Lower WMS MQ were associated with CCD (Chi2 5.9; p<.01; Fisher test p<.02. Lower WAIS IQ were associated with CCD (Chi2 6.3, p<.01; Fisher test p<.01 being the digit symbol (p<.03, picture completion (p<.03, picture arrangement (p<.01 and object assembly (p<.03 subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.
The contribution of cerebrovascular disease in the development of cognitive dysfunction and dementia is increasingly recognized. Cerebrovascular damage is heterogeneous, ranging from a clinical stroke to more insidious brain changes. The term vascular cognitive impairment (VCI) has been introduced,
Full Text Available Multiple sclerosis (MS is a common inflammatory demyelinating disease that affects the central nervous system (CNS. It may be accompanied by cognitive impairment, however, the mechanism for cognitive impairment in multiple sclerosis is still unknown. More and more MRI techniques are used to improve the understanding on pathogenetic mechanism of cognitive impairment in multiple sclerosis. This paper summarizes MRI measures currently available to explain the possible mechanism for cognitive impairment of multiple sclerosis. DOI: 10.3969/j.issn.1672-6731.2016.04.012
Xiaofang Chen; Yueji Sun; Haiyan Liu; Yunqiao Ding; Shujuan Liu; Jinghua Chen; Xueying Wang; Zhenpeng Han; Fang Qu
BACKGROUND: Cognitive impairment after stroke associates with various factors, such as age, educational years, etc. Besides concerning about the recovery of limb function after stroke, we should also focus on the rehabilitation of cognition. Moreover, we'd better pay attention to the control of all the risk factors of stroke, and improve the quality of life in stroke patients.OBJECTIVE: To analyze the factors that affect cognitive impairment after stroke.DESIGN: A related factors analysis.SET-FINGS: Department of Neurology of Dalian Port Hospital and Dalian Second People's Hospital.PARTICIPANTS: Totally 148 stroke inpatients were selected from Department of Neurology, Dalian Port Hospital and Dalian Second People's Hospital from April 2004 to December 2005, including 100 males and 48females, aging 45-75 years with an average age of (67±8) years; Their educational years ranged 2-10 years with an average of (6.1 ±3.7) years; The disease course ranged 15-30 days; All were right-handed. Inclusive criteria: All were accorded with the diagnostic standard set by the Fourth National Academic Meeting for Cerebrovascular Disease; Confirmed by CT or MRI; Informed consents were obtained from all the subjects.METHODS: After the disease conditions were stable, the patients were assessed with Wechsler memory scale (WMS) and Wisconsin card sorting test (WCST). WMS included forward and backward recitation of numbers and short-term memory (verbal memory, visual recognition). The number of times for correct and wrong classifications in WCST and the time to complete the trail making tests A and B were recorded. The focal volume, area and layer were recorded at 24 hours after admission. The general data of the patients were recorded, including name, sex, age, educational years, history of hypertension, history of diabetes mellitus.Electroencepalograph (EEC) was examined to record the wave shape, blood lipids were detected, and the cognition related indexes were analyzed with the
Consuelo H Wilkins
Full Text Available Consuelo H Wilkins1,2, Jose Mathews2, Yvette I Sheline21Department of Medicine (Division of Geriatrics and Nutritional Science; 2Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USAAbstract: Older adults with depression often present with signs and symptoms indicative of functional or cognitive impairment. These somatic symptoms make evaluating and treating depression in older adults more complex. Late life depression (LLD, depression in adults over the age of 65, is more frequently associated with cognitive changes. Cognitive impairment in LLD may be a result of the depressive disorder or an underlying dementing condition. Memory complaints are also common in older adults with depression. There is a wide range of cognitive impairment in LLD including decreased central processing speed, executive dysfunction, and impaired short-term memory. The etiology of cognitive impairment in LLD may include cerebrovascular disease, a significant risk factor for LLD, which likely interrupts key pathways between frontal white matter and subcortical structures important in mood regulation. Because depressive symptoms often coexist with dementia, it is important to determine the temporal relationship between depressive symptoms and cognitive change. If depressive symptoms pre-date the cognitive impairment and cognitive symptoms are mild and temporary, LLD is the likely etiology of the cognitive impairment. If cognitive changes appear prior to depressive symptoms and persist after LLD is successfully treated, an underlying dementia is more likely. Clinicians should be exclude common conditions such as thyroid disease which can contribute to depressive symptoms and cognitive impairment prior to treating LLD. Both antidepressants and psychotherapy can be effective in treating LLD. Subsequent evaluations following treatment should also reassess cognition.Keywords: late life depression, cognitive impairment, diagnosis, treatment
Pedersen, Mette; Holt, Nicole E; Grande, Laura
BACKGROUND: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. METHODS......MCI), nonmemory domains (naMCI), and multiple domains (mdMCI). Linear regression models were used to assess the association between MCI status and mobility performance in the Habitual Gait Speed, Figure of 8 Walk, Short Physical Performance Battery, and self-reported Late Life Function and Disability Instrument......). All MCI subtypes performed significantly worse than No-MCI on all mobility measures (p Figure of 8 Walk (p = .054) and Basic Lower Extremity (p = .11). Moreover, compared with aMCI, mdMCI manifested worse performance on the Figure of 8 Walk and Short...
Vogel, Asmus; Stokholm, Jette; Gade, Anders
In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...
Bora, Emre; Yücel, Murat; Pantelis, Christos
It has recently been suggested that cognitive impairment should be included in the diagnostic criteria of schizophrenia. One of the main arguments in support of this suggestion has been the hope that cognitive impairment can help distinguish schizophrenia from bipolar disorder (BD). However, recent evidence shows that cognitive deficits occur in BD and persist beyond euthymia. Further, mood disorders with psychotic features might be expected to manifest greater cognitive impairment, which further complicates the potential to differentiate these disorders. The goal of the current meta-analysis was to examine the magnitude and characteristics of cognitive impairments in affective psychoses (AP). A systematic search of the existing literature sourced 27 studies that met the inclusion criteria. These studies compared cognitive performances of 763 patients with AP (550 BD and 213 major depressive disorder) and 1823 healthy controls. Meta-regression and subgroup analyses were used to examine the effects of moderator variables. Meta-analyses of these studies showed that patients with AP were impaired in all 15 cognitive tasks with large effect sizes for most measures. There were no significant differences between the magnitude of impairments between the BD and major depressive disorder groups. The largest effect size was found for symbol coding, stroop task, verbal learning, and category fluency, reflecting impairments in elementary and complex aspects of attentional processing, as well as learning and memory. In general, the pattern of cognitive impairments in AP was similar to reported findings in euthymic patients with BD, but relatively more pronounced.
Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James
White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…
Dittrich, Kerstin; Stahl, Christoph
Load theory predicts that concurrent cognitive load impairs selective attention. For visual stimuli, it has been shown that this impairment can be selective: Distraction was specifically increased when the stimulus material used in the cognitive load task matches that of the selective attention task. Here, we report four experiments that…
McConnell, David; Feldman, Maurice; Aunos, Marjorie; Prasad, Narasimha
Objectives: The aim of this study was to determine the prevalence of parental cognitive impairment in cases opened for child maltreatment investigation in Canada, and to examine the relationship between parental cognitive impairment and maltreatment investigation outcomes including substantiation, case disposition and court application. Methods:…
Kim, Eunji; Ko, Hae Ju; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Ha Neul; Woo, Eun-Rhan; Ryu, Jong Hoon
Erucic acid is a monounsaturated omega-9 fatty acid isolated from the seed of Raphanus sativus L. that is known to normalize the accumulation of very long chain fatty acids in the brains of patients suffering from X-linked adrenoleukodystrophy. Here, we investigated whether erucic acid enhanced cognitive function or ameliorated scopolamine-induced memory impairment using the passive avoidance, Y-maze and Morris water maze tasks. Erucic acid (3mg/kg, p.o.) enhanced memory performance in normal naïve mice. In addition, erucic acid (3mg/kg, p.o.) ameliorated scopolamine-induced memory impairment, as assessed via the behavioral tasks. We then investigated the underlying mechanism of the memory-enhancing effect of erucic acid. The administration of erucic acid increased the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K), protein kinase C zeta (PKCζ), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and additional protein kinase B (Akt) in the hippocampus. These results suggest that erucic acid has an ameliorative effect in mice with scopolamine-induced memory deficits and that the effect of erucic acid is partially due to the activation of PI3K-PKCζ-ERK-CREB signaling as well as an increase in phosphorylated Akt in the hippocampus. Therefore, erucic acid may be a novel therapeutic agent for diseases associated with cognitive deficits, such as Alzheimer's disease.
Allen, Nara L.
The aim of the present study was to investigate the effects of a computer cognitive training program on depression levels in older mildly cognitive impaired individuals. Peterson et al. (1999), defines mild cognitive impairment (MCI) as a transitional stage in which an individual's memory deteriorates and his likelihood of developing Alzheimer's…
Xiaohan Xu; Leilei Guo; Guoqing Tian
The problem of cognitive impairment resulting from diabetes is gaining more acceptance and attention. Both type 1 and type 2 diabetes mellitus have been proved to be associated with reduced performance on numerous domains of cognitive function. Although the exact mechanisms of cognitive impairments in diabetes have not been completely understood, hyperglycemia and insulin resistance seem to play significant roles. And other possible risk factors such as hypoglycemia, insulin deficiency, vascu...
Blake, Holly; McKinney, Michelle; Treece, Karen; Lee, Elizabeth; Lincoln, Nadina B.
Objectives: to assess the sensitivity and specificity of a screening battery for detecting cognitive impairment after stroke. Design: a randomized controlled trial. Methods: stroke patients were recruited from hospitals in three centres. Patients were screened for cognitive impairment on the Mini‐Mental State Examination, the Sheffield Screening Test for Acquired Language Disorders and Raven's Coloured Progressive Matrices and received a further battery of assessments of cognitive f...
Nedergaard, H K; Jensen, H I; Toft, P
BACKGROUND: Critical illness is associated with cognitive impairments. Effective treatment or prevention has not been established. The aim of this review was to create a systematic summary of the current evidence concerning clinical interventions during intensive care admission to reduce cognitive...... and sleep quality improvement. Data were synthesized to provide an overview of interventions, quality, follow-up assessments and neuropsychological outcomes. CONCLUSION: None of the interventions had significant positive effects on cognitive impairments following critical illness. Quality was negatively...
Cerebral vascular disease (CVD) is an important cause of cognitive decline and dementia, either alone or in combination with neurodegenerative diseases, such as Alzheimer's Disease (AD). The contribution of CVD to cognitive decline and dementia is referred to as Vascular Cognitive Impairment (VCI).
Full Text Available Amyloid-β peptide (Aβ is known to be directly associated with the progressive neuronal death observed in Alzheimer’s disease (AD. However, effective neuroprotective approaches against Aβ neurotoxicity are still unavailable. In the present study, we investigated the protective effects of Akebia saponin D (ASD, a typical compound isolated from the rhizome of Dipsacus asper Wall, on Aβ1–42-induced impairment of learning and memory formation and explored the probable underlying molecular mechanisms. We found that treatment with ASD (30, 90 or 270 mg/kg significantly ameliorated impaired spatial learning and memory in intracerebroventricularly (ICV Aβ1–42-injected rats, as evidenced by a decrease tendency in escape latency during acquisition trials and improvement in exploratory activities in the probe trial in Morris water maze (MWM. Further study showed that ASD reversed Aβ1–42-induced accumulation of Aβ1–42 and Aβ1–40 in the hippocampus through down-regulating the expression of BACE and Presenilin 2 accompanied with increased the expression of TACE, IDE and LRP-1. Taken together, our findings suggested that ASD exerted therapeutic effects on Aβ-induced cognitive deficits via amyloidogenic pathway.
Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong
Post-operative cognitive dysfunction (POCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain β-amyloid (Aβ) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The Aβ accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2α. γ-Secretase inhibitor compound E ameliorated the surgery-induced brain Aβ accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging- or Alzheimer gene mutation-associated Aβ accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD.
Zhao, Jingjing; Yao, Li; Wang, Changqing; Sun, Yun; Sun, Zhongwu
Patients who survive critical illness commonly suffer cognitive impairments. We aimed to study the effects of cognitive intervention to treat the long-term impairments observed among different populations of intensive care unit (ICU) survivors. The results showed that the intervention significantly suppressed the deterioration of cognitive function in these patients. Medical and neurological ICU survivors were more susceptible than post-anaesthesia ICU patients to severe cognitive damage. In the former, the deterioration of impairments can be slowed by cognitive intervention. In comparison, intervention exerted significantly positive effects on the recovery of the cognitive functions of post-anaesthesia care unit patients. Furthermore, young populations were more likely than older populations to recover from acute cognitive impairments, and the impairment observed among the older population seemed to be multi-factorial and irreversible.
Jellinger, Kurt A
Cognitive impairment is common in Parkinson disease (PD), with long-term longitudinal studies reporting that most PD patients develop dementia. A high proportion of patients with PD and mild cognitive impairment (MCI) progress to dementia within a short time. Impairments occur in a range of cognitive domains, but single-domain impairment is more common than multiple one, non-amnestic more common than amnestic impairment. Although the term MCI applied to PD (PD-MCI) is not without controversy due to the lack of uniform diagnostic consensus criteria, the biological validity of PD-MCI is supported by many recent studies that show heterogenous mechanisms in the clinical presentation, neuropsychology, neuroimaging, biomarkers, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical nervous systems. Prospective studies using specific biomarkers, including amyloid imaging, and cerebro-spinal fluid biomarkers are warranted for an exact diagnosis and prognostic assessment of early cognitive deficits in PD patients.
Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Martinez, Ana; Faghihi, Mohammad A.; Jope, Richard S.; Beurel, Eleonore
Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA– or HDAC4 siRNA–induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1–/– mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets. PMID:28352664
Horstmann, Solveig; Rizos, Timolaos; Rauch, Geraldine; Fuchs, Maximilian; Arden, Cathrin; Veltkamp, Roland
Dementia and atrial fibrillation (AF) are common comorbidities in stroke patients. The potential role of AF in cognitive impairment prior to a first stroke has yet not been characterized. The aim of our study was to evaluate the prevalence of prestroke cognitive impairment in stroke patients, and to identify whether AF is associated with prestroke cognitive impairment. In this prospective, single-center, explorative, observational study, consecutive patients with first ever transient ischemic attack (TIA), ischemic (IS) or hemorrhagic stroke (ICH) were included. For each patient cardiovascular risk factors and the National Institutes of Health Stroke Scale were recorded. Cognitive status prior to the stroke/TIA was assessed using the informant questionnaire on cognitive decline in the elderly (IQCODE). AF was diagnosed according to a standardised procedure that included the documented medical history, ECG upon admission, 24-h Holter-ECG, continuos ECG monitoring, and was categorized into paroxysmal and persistent. Logistic regression analysis was used to evaluate association of AF and prestroke cognitive impairment. A total of 788 patients were enrolled in our study. Of these, 548 (69.5 %) had an IS, TIA was present in 168 (21.3 %) and ICH in 72 (9.1 %) patients. Mean IQCODE was 3.1 (SD 0.4). Prestroke cognitive impairment (IQCODE ≥3.44) was detected in 96 (12.5 %) patients. Of these, 33 patients (4.3 %) were demented before the actual stroke event. AF was independently associated with prestroke cognitive impairment. Patients with an acute stroke frequently show a history of cognitive impairment before the event. AF is independently associated with prestroke cognitive impairment.
Full Text Available Mild cognitive impairment is understood as a cognitive deficit of insufficient severity to fulfil the criteria for Alzheimer’s disease. Many studies have attempted to identify which cognitive functions are most affected by this type of impairment and which is the most sensitive neuropsychological test for early detection. This study investigated sustained and selective attention, processing speed, and the inhibition process using a sample of people divided into three groups mild cognitive impairment, Alzheimer disease and cognitively healthy controls selected and grouped based on their scores in the Mini Mental State Examination and Cambridge Cognitive Examination-revised. Three tests from the Cambridge Neuropsychological Test Automated Battery (Motor Screening Task, Stop Signal Task and Reaction time were used as well as the d2 attention test. The results show that that participants with mild cognitive impairment and Alzheimer disease showed lower levels of concentration compared with the cognitively healthy controls group in the d2 test and longer reaction times in the Cambridge Neuropsychological Test Automated Battery, although the differences were not marked in the latter test. The impairments in basic cognitive processes, such as reaction time and sustained attention, indicate the need to take these functions into account in the test protocols when discriminating between normal aging and early and preclinical dementia processes.
José Ibiapina Siqueira- Neto
Full Text Available ABSTRACT Pemphigus vulgaris is a systemic auto-immune medical condition that mainly manifests with changes in skin and vasculopathy. This is a case report of a 69-year-old male with confirmed histopathologic diagnosis of Pemphigus vulgaris presenting ulterior Cognitive Impairment, mostly in executive function. The patient was treated using steroids, immunomodulatory therapy, fluoxetine and galantamine. Neuropsychological testing and magnetic resonance (MRI were performed. This is the first report of correlational cognitive impairment with Pemphigus vulgaris in the literature. Physicians should be aware of vascular causes for cognitive impairment in patients presenting auto-immune conditions.
Rahel Bieri[1; Michael Jager[1; Nora Bethencourt[1; Urs Peter Mosimann[1,2; Rene Martin Mari[1,3; Tobias Nef[3,4
Intact cognitive abilities are fundamental for driving. Driving-relevant cognition may be affected in older drivers due to aging or cognitive impairment. The aim of this study was to investigate the effects of cognitive impairment on driving-relevant cognition in older persons. Performance in selective and divided attention, eye-hand-coordination, executive functions and the ability to regulate distance and speed of 18 older persons with CI-Group （cognitive impairment group） was compared to performance of older control group （18 age and gender-matched cognitively normal subjects） and young control group （18 gender-matched young subjects）. The CI-Group showed poorer performance than the other two control groups in all cognitive tasks （significance level （p） 〈 0.001, effect size （partial r/e） = 0.63）. Differences between cognitively impaired and cognitively normal subjects were still significant after controlling for age （effect sizes from 0.14 to 0.28）. Dual tasking affected performance of cognitively impaired subjects more than performance of the other two groups （p = 0.016, partial η2 = 0.14）. Results show that cognitive impairment has age-independent detrimental effects on selective and divided attention, eye-hand-coordination, executive functions and the ability to regulate distance and speed. Largest effect sizes are found for reaction times in attention tasks.
Zhang Qiujuan; Yao Xiaoxin; Guo Youmin; Zhang Gejuan; Yang Junle
Objective To study the relationships between cognitive impairment in patients with lacunar infarcts and quantitative CT measures and to determine the independent correlative factors of cognitive impairment. Methods Neuropsychological examination was conducted for 128 patients with acute lacunar infarct. Number, location, and volume of infarcts, cerebral atrophy index and severity of white matter lesions (WMLs) were measured and recorded. Results The number of lacunar infarcts in cognitive impairment (CI) group was significantly larger than that in cognitive normal (CN) group. Mean width of sulcus and sylvian fissure, index of frontal horn and ventricular-brain ratio (VBR) were significantly different in both groups. There were more patients with 3 grades or 4 grades WMLs in CI group (62%) than those in CN group (22%). The total volume of lacunar infarcts showed no statistically significant difference. Logistic regression analysis indicated that the number of lacunar infarcts in frontal subcortex and thalamus, the volume of infarcts in anterior periventricular white matter, width of cerebral sulcus and sylvian fissure were correlated with cognitive impairment respectively. Additionally, age and education were correlative factors of cognitive impairment in patients with lacunar infarct. Conclusion Correlative factors of cognitive impairment in patients with lacunar infarct are not merely one feature, but a combination of infarct features (number, location, and volume), cortical atrophy and host factors (age and education).
Mariegold E. Wollam
Full Text Available Introduction. A family history of Alzheimer’s disease is a significant risk factor for its onset, but the genetic risk associated with possessing multiple risk alleles is still poorly understood. Methods. In a sample of 95 older adults (Mean age = 75.1, 64.2% female, we constructed a genetic risk score based on the accumulation of risk alleles in BDNF, COMT, and APOE. A neuropsychological evaluation and consensus determined cognitive status (44 nonimpaired, 51 impaired. Logistic regression was performed to determine whether the genetic risk score predicted cognitive impairment above and beyond that associated with each gene. Results. An increased genetic risk score was associated with a nearly 4-fold increased risk of cognitive impairment (OR = 3.824, P = .013 when including the individual gene polymorphisms as covariates in the model. Discussion. A risk score combining multiple genetic influences may be more useful in predicting late-life cognitive impairment than individual polymorphisms.
Full Text Available We previously reported that Fructus mume (F. mume extract shows protective effects on memory impairments and anti-inflammatory effects induced by chronic cerebral hypoperfusion. Neurodegeneration of basal cholinergic neurons is also observed in the brain with chronic cerebral hypoperfusion. Therefore, the present study was conducted to examine whether F. mume extracts enhance cognitive function via the action of cholinergic neuron using a scopolamine-induced animal model of memory impairments. F. mume (50, 100, or 200 mg/kg was administered to C57BL/6 mice for 14 days (days 1–14 and memory impairment was induced by scopolamine (1 mg/kg, a muscarinic receptor antagonist for 7 days (days 8–14. Spatial memory was assessed using Morris water maze and hippocampal level of acetylcholinesterase (AChE and choline acetyltransferase (ChAT was examined by ELISA and immunoblotting. Mice that received scopolamine alone showed impairments in acquisition and retention in Morris water maze task and increased activity of AChE in the hippocampus. Mice that received F. mume and scopolamine showed no scopolamine-induced memory impairment and increased activity of AChE. In addition, treatments of F. mume increased ChAT expression in the hippocampus. These results indicated that F. mume might enhance cognitive function via action of cholinergic neurons.
Full Text Available Magdalena I Tolea,1 James E Galvin1–3 1Alzheimer’s Disease Center, Department of Neurology, 2Department of Psychiatry, 3Department of Population Health, New York University School of Medicine, New York, NY, USA Background: Whether older adults with sarcopenia who underperform controls on tests of physical performance and cognition also have a higher likelihood of combined cognitive-physical impairment is not clear. We assessed the impact of sarcopenia on impairment in both aspects of functionality and the relative contribution of its components, muscle mass and strength.Methods: Two hundred and twenty-three community-dwelling adults aged 40 years and older (mean age =68.1±10.6 years; 65% female were recruited and underwent physical functionality, anthropometry, and cognitive testing. Participants with low muscle mass were categorized as pre-sarcopenic; those with low muscle mass and muscle strength as sarcopenic; those with higher muscle mass and low muscle strength only were categorized as non-sarcopenic and were compared on risk of cognitive impairment (Montreal Cognitive Assessment <26; Ascertaining Dementia 8 ≥2, physical impairment (Mini Physical Performance Test <12, both, or neither by ordinal logistic regression. Results: Compared to controls, those with sarcopenia were six times more likely to have combined cognitive impairment/physical impairment with a fully adjusted model showing a three-fold increased odds ratio. The results were consistent across different measures of global cognition (odds ratio =3.46, 95% confidence interval =1.07–11.45 for the Montreal Cognitive Assessment; odds ratio =3.61, 95% confidence interval =1.11–11.72 for Ascertaining Dementia 8. Pre-sarcopenic participants were not different from controls. The effect of sarcopenia on cognition is related to low muscle strength rather than low muscle mass. Conclusion: Individuals with sarcopenia are not only more likely to have single but also to have dual
Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun
Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.
Russo, C; Morabito, F; Luise, F; Piromalli, A; Battaglia, L; Vinci, A; Trapani Lombardo, V; de Marco, V; Morabito, P; Condino, F; Quattrone, A; Aguglia, Umberto
Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease.
Delgado-Alvarado, Manuel; Gago, Belén; Navalpotro-Gomez, Irene; Jiménez-Urbieta, Haritz; Rodriguez-Oroz, María C
Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society.
Renvillard, Signe Groth; Leutscher, Peter; Hjerrild, Simon;
Impaired cognitive function is commonly seen in patients with hepatitis C-virus (HCV). This might be due to a toxic effect of the virus itself or to neuroinflammatory processes with a direct damaging cerebral effect. The symptoms appear in the pre-cirrhotic stage and impair the patient's level...
Rooij, F.G. van; Kessels, R.P.C.; Richard, E.; Leeuw, H.F. de; Dijk, E.J. van
Background: Although by definition a transient ischemic attack (TIA) lasts less than 24 h, many patients experience cognitive complaints beyond focal symptom resolution. However, their prevalence, causes and profile are unclear. We therefore performed a systematic review on cognitive impairment afte
Mild cognitive impairment in Parkinson disease (PD-MCI) shows heterogeneity in the clinical presentation, neuropsychology, neuroimaging, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical systems. Prospective studies using specific biomarkers, including amyloid imaging and CSF biomarkers are important for the diagnosis and prognostic assessment of early cognitive deficits in PD patients.
Full Text Available Advanced carotid disease is known to be associated with symptomatic cerebrovascular diseases, such as stroke or transient ischemic attack (TIA, as well as with poststroke cognitive impairment. However, cognitive decline often occurs in patients with advanced carotid stenosis without clinically evident stroke or TIA, so it is also suspected to be an independent risk factor for dementia. Neurosonological methods enable simple and noninvasive assessment of carotid stenosis in patients at risk of advanced atherosclerosis. Cognitive status in patients diagnosed with advanced carotid stenosis is routinely not taken into consideration, although if cognitive impairment is present, such patients should probably be called symptomatic. In this paper, we discuss results of some most important studies that investigated cognitive status of patients with asymptomatic advanced carotid disease and possible mechanisms involved in the causal relationship between asymptomatic advanced carotid disease and cognitive decline.
Shields, Grant S; Trainor, Brian C; Lam, Jovian C W; Yonelinas, Andrew P
Psychosocial stress influences cognitive abilities, such as long-term memory retrieval. However, less is known about the effects of stress on cognitive flexibility, which is mediated by different neurobiological circuits and could thus be regulated by different neuroendocrine pathways. In this study, we randomly assigned healthy adults to an acute stress induction or control condition and subsequently assessed participants' cognitive flexibility using an open-source version of the Wisconsin Card Sort task. Drawing on work in rodents, we hypothesized that stress would have stronger impairing effects on cognitive flexibility in men than women. As predicted, we found that stress impaired cognitive flexibility in men but did not significantly affect women. Our results thus indicate that stress exerts sex-specific effects on cognitive flexibility in humans and add to the growing body of research highlighting the need to consider sex differences in effects of stress.
Mizoguchi, Hiroyuki; Ibi, Daisuke; Takase, Fumiaki; Nagai, Taku; Kamei, Hiroyuki; Toth, Erika; Sato, Jun; Takuma, Kazuhiro; Yamada, Kiyofumi
Nicotine is hypothesized to have therapeutic effects on attentional and cognitive abnormalities in psychosis. In this study, we investigated the effect of nicotine on impaired spatial working memory in repeated methamphetamine (METH)-treated rats. Rats were administered METH (4 mg/kg, s.c.) once a day for 7 days, and their working memory was assessed with a delayed spatial win-shift task in a radial arm maze. The task consisted of two phases, a training phase and a test phase, separated by a delay. Control animals showed impaired performance in the test phase when the delay time was increased to 120 min or longer, while METH-treated rats showed impaired performance with a shorter delay time of 90 min. Memory impairment in METH-treated rats persisted for at least 14 days after drug withdrawal. METH-induced impairment of working memory was reversed by nicotine (0.3mg/kg, p.o., for 7 days), but the effect was diminished 7 days after the withdrawal. In control rats, nicotine decreased the number of working memory errors in the test with delay time of 120 min when administered before the training phase. Neither post-training nor pre-test administration of nicotine had any effect on working memory. These findings suggest that nicotine may have some protective effect against the impairment of working memory.
Nawata, Yoko; Hiranita, Takato; Yamamoto, Tsuneyuki
(+/-)-3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') abusers have persistent neuropsychiatric deficits including memory impairments after the cessation of abuse. On the other hand, cannabinoid CB(1) receptors have been implicated in learning/memory, and are highly expressed in the hippocampus, a region of the brain believed to have an important function in certain forms of learning and memory. In this study, we clarified the mechanism underlying the cognitive impairment that develops during MDMA withdrawal from the standpoint of the cannabinoid CB(1) receptors. Mice were administered MDMA (10 mg/kg, i.p.) once a day for 7 days. On the 7th day of withdrawal, a novel object recognition task was performed and the amount of cannabinoid CB(1) receptor protein was measured with western blotting. Recognition performance was impaired on the 7th day of withdrawal. This impairment was blocked by AM251, a cannabinoid CB(1) receptor antagonist, administered 30 min before the training trial or co-administered with MDMA. At this time, the level of cannabinoid CB(1) receptor protein increased significantly in the hippocampus but not the prefrontal cortex or striatum. This increase of CB(1) receptor protein in the hippocampus was also blocked by the co-administration of AM251. Furthermore, CB(1) receptor knockout mice showed no impairment of recognition performance on the withdrawal from MDMA. The impairment of recognition memory during withdrawal from MDMA may result from the activation of cannabinoid CB(1) receptors in the hippocampus.
Lin, Chun-Yuan; Tsai, Guochuan E; Lane, Hsien-Yuan
Schizophrenia is a serious neuropsychiatric disease characterized by positive symptoms, negative symptoms and cognitive impairment. Evidence have shown that cognitive impairment sustains in every clinical stage, may relate with the liability, may predict functional outcome in schizophrenia and could be the core symptom of schizophrenia. The treatment of cognitive impairment in schizophrenia could alleviate the burden of the illness and has become the subject of intensive research. In this review, we synthesize current advances of assessing strategies, pharmacological and non-pharmacological treatments of cognitive impairment in schizophrenia. According to the registered records of ClinicalTrials.gov, the most widely studied strategies have aimed at modifying neurochemical mechanisms of dopamine metabolism, glutamate metabolism, γ-aminobutyric acid (GABA) metabolism, serotonin metabolism, acetylcholine metabolism, and oxytocin. Despite preclinical data for putative pro-cognitive drugs, their clinical benefits for schizophrenia patients have been limited. The small sample sizes and the short treatment duration could be related with the suboptimal results. Evidence supported the short-term benefits of cognitive remediation therapy on cognitive domains with small to moderate effects; however, the small sample sizes and the characteristics of subjects limited the generalization of the positive results and the long-term functional outcome is not clear. Combination therapy is promising, by integrating pro-cognitive agents and cognitive rehabilitation programs or combining two kinds of pro-cognitive agents via different mechanisms. Future studies should investigate the pro-cognitive drugs' long-term efficacy, rebound deterioration in psychosis/cognition following discontinuation, and related biomarkers of functional outcome.
Caroline Martins de Araújo
Full Text Available ABSTRACT Patients with migraine often report cognitive complaints, especially regarding attention and memory. Objective: To perform a systematic review of the studies available on cognitive evaluation in patients with migraine. Methods: We evaluated all articles containing the key words: "Migraine", "Cognition" and "Cognitive Impairment." Results: The search strategy resulted in 23 articles. Fifteen out of the 23 studies (65.3% retrieved reported abnormalities on neuropsychological tests in migraine patients, notably tests of memory, attention and information processing speed. Most of the studies showing cognitive changes in migraine were carried out in neurological care facilities. Conversely, among community-based studies, migraine patients were less likely to present cognitive changes. Conclusion: Patients with migraine, especially those followed at neurology clinics, show an elevated risk of mild changes in several cognitive domains. Further studies with greater methodological refinement are warranted in order to clearly establish whether this cognitive dysfunction is associated with an underlying migraine pathophysiological process.
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.
I. V. Rogova
Full Text Available Objective: to study the specific features of development of cognitive impairments (CIs, the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD and to assess an association of CIs with the signs of vascular wall remodeling in them. Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR of і60 ml/min/1.73 m2, signs of renal lesion; 20 with Stages III CKD: a GFR of <60–30 ml/min/1.73 m2, and 11 with Stages VI CKD: a GFR of <30–15 ml/min/1.73 m2. Results and discussion. CIs were more common in the patients with Stages III–IV than in those with Stages I–II, as shown by the scores of the mini-mental state examination (p<0.001, the frontal assessment battery (p=0.001, and the regulatory function test (p<0.001. These tests showed that the magnitude of CIs increased with the higher stage of CKD. Stages III–IV CKD is an independent predictor of CIs in persons with predialysis-stage kidney lesion. CIs were found to be related to hyperhomocysteinemia, anemia, abdominal obesity, left ventricular hypertrophy, and patient age. The signs of atherosclerotic lesion of the common carotid arteries and the indicators of arterial stiffness were also associated with the incidence and magnitude of CIs in CKD. The detection of CIs in patients with early CKD allows one to timely initiate adequate therapy aimed particularly at improving cerebral circulation, eliminating the impact of risk factors, and slowing down the vascular remodeling. The management tactics for patients with CKD must involve the identification and correction of cardiovascular risk factors, and duplex scanning of the wall of the common carotid arteries may be used as a noninvasive method to assess the risk of the development and progression of CIs in predialysis CKD.
Full Text Available Alexandra M Hajduk,1,2 Stephenie C Lemon,3 David D McManus,1,2,4 Darleen M Lessard,1 Jerry H Gurwitz,1,2,4 Frederick A Spencer,5 Robert J Goldberg,1,2 Jane S Saczynski1,2,4 1Division of Epidemiology of Chronic Diseases and Vulnerable Populations, Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA; 2Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, MA, USA; 3Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA; 4Division of Geriatric Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA; 5Department of Medicine, McMaster University, Hamilton, ON, Canada Background: Heart failure (HF is a prevalent chronic disease in older adults that requires extensive self-care to prevent decompensation and hospitalization. Cognitive impairment may impact the ability to perform HF self-care activities. We examined the association between cognitive impairment and adherence to self-care in patients hospitalized for acute HF. Design: Prospective cohort study. Setting and participants: A total of 577 patients (mean age = 71 years, 44% female hospitalized for HF at five medical centers in the United States and Canada. Measurements and methods: Participants were interviewed for information on self-reported adherence to self-care using the European Heart Failure Self-care Behaviour Scale. We assessed cognitive impairment in three domains (memory, processing speed, and executive function using standardized measures. Patients' demographic and clinical characteristics were obtained through medical record review. Multivariable linear regression was used to examine the association between cognitive impairment and self-care practices adjusting for demographic and clinical factors. Results: A total of 453 patients (79% were impaired in at least one cognitive
Oliva, Jesus; Serrano, J Ignacio; del Castillo, M Dolores; Iglesias, Angel
Specific Language Impairment (SLI), as many other cognitive deficits, is difficult to diagnose given its heterogeneous profile and its overlap with other impairments. Existing techniques are based on different criteria using behavioral variables on different tasks. In this paper we propose a methodology for the diagnosis of SLI that uses computational cognitive modeling in order to capture the internal mechanisms of the normal and impaired brain. We show that machine learning techniques that use the information of these models perform better than those that only use behavioral variables.
Full Text Available The result of neuropsychological tests is crucial to confirm a diagnosis of dementia or cognitive impairment. It might be improper judging individuals with different basic cognitive function using the same standard. The evaluation of premorbid intelligence is an effective way for error correction, but not enough attention has been paid during clinical practice. Here we present a review of the existing methods of premorbid intelligence evaluation and their application in cognitive impairment. DOI: 10.3969/j.issn.1672-6731.2016.09.016
Mossello, Enrico; Simoni, David
High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment.
Hunsaker, Amanda E; Terhorst, Lauren; Gentry, Amanda; Lingler, Jennifer H
The current exploratory investigation aims to establish the reliability and validity of a hope measure, the Herth Hope Index, among families impacted by early cognitive impairment (N = 96). Exploratory factor analysis was used to examine the dimensionality of the measure. Bivariate analyses were used to examine construct validity. The sample had moderately high hope scores. A two-factor structure emerged from the factor analysis, explaining 51.44% of the variance. Both factors exhibited strong internal consistency (Cronbach's alphas ranged from .83 to .86). Satisfaction with social support was positively associated with hope, supporting convergent validity. Neurocognitive status, illness insight, and depression were not associated with hope, indicating discriminant validity. Families impacted by cognitive impairment may maintain hope in the face of a potentially progressive illness, regardless of cognitive status. The Herth Hope Index can be utilized as a reliable and valid measure of hope by practitioners providing support to families impacted by cognitive impairment.
Rashid, Mohammad Abdur; Kim, Hee-Yong
Previous studies demonstrated that prenatal exposure to ethanol interferes with embryonic and fetal development, and causes abnormal neurodevelopment. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid highly enriched in the brain, was shown to be essential for proper brain development and function. Recently, we found that N-docosahexenoyethanolamine (synaptamide), an endogenous metabolite of DHA, is a potent PKA-dependent neurogenic factor for neural stem cell (NSC) differentiation. In this study, we demonstrate that ethanol at pharmacologically relevant concentrations downregulates cAMP signaling in NSC and impairs neurogenic differentiation. In contrast, synaptamide reverses ethanol-impaired NSC neurogenic differentiation through counter-acting on the cAMP production system. NSC exposure to ethanol (25-50 mM) for 4 days dose-dependently decreased the number of Tuj-1 positive neurons and PKA/CREB phosphorylation with a concomitant reduction of cellular cAMP. Ethanol-induced cAMP reduction was accompanied by the inhibition of G-protein activation and expression of adenylyl cyclase (AC) 7 and AC8, as well as PDE4 upregulation. In contrast to ethanol, synaptamide increased cAMP production, GTPγS binding, and expression of AC7 and AC8 isoforms in a cAMP-dependent manner, offsetting the ethanol-induced impairment in neurogenic differentiation. These results indicate that synaptamide can reduce ethanol-induced impairment of neuronal differentiation by counter-affecting shared targets in G-protein coupled receptor (GPCR)/cAMP signaling. The synaptamide-mediated mechanism observed in this study may offer a possible avenue for ameliorating the adverse impact of fetal alcohol exposure on neurodevelopment.
Fernanda Fiel Peres
Full Text Available Cannabidiol (CBD is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg or vehicle (days 2-5. On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.
Peres, Fernanda F.; Levin, Raquel; Suiama, Mayra A.; Diana, Mariana C.; Gouvêa, Douglas A.; Almeida, Valéria; Santos, Camila M.; Lungato, Lisandro; Zuardi, Antônio W.; Hallak, Jaime E. C.; Crippa, José A.; Vânia, D’Almeida; Silva, Regina H.; Abílio, Vanessa C.
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2–5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements, and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia. PMID:27733830
Full Text Available Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer's disease. The subjects in this study were 39 Alzheimer's disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer's disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer's disease.
Hasanein, Parisa; Mahtaj, Azam Kazemian
Rosmarinic acid (RA) is a natural phenol that exerts different biological activities, such as antioxidant activity and neuroprotective effects. In this study, we hypothesized that administration of RA (8, 16, and 32 mg/kg, p.o.) for 7 days would effect on scopolamine-induced cognitive dysfunction as an extensively used model of cognitive impairment. The rats were divided into 10 groups. The acquisition trial was done 1h after the last administration of RA. Animals were divided into control, RA (8, 16, and 32 mg/kg) and donepezil (2 mg/kg) treated controls, scopolamine, RA (8, 16, and 32 mg/kg), and donepezil (2 mg/kg) treated scopolamine groups. Memory impairment was induced by scopolamine treatment (1 mg/kg, i.p.) 30 min after the administration of RA, donepezil, or saline. Scopolamine administration caused cognition deficits in the PAL and memory paradigm. While orally RA administration (16 and 32 mg/kg) improved learning and memory in control rats, it reversed learning and memory deficits of scopolamine received groups. Administration of RA at the dose of 8 mg/kg did not alter cognitive function in control and scopolamine treated groups. The combination of anticholinesterase, neuroprotective, and antioxidant properties of RA may all be responsible for the observed effects. These results indicate the beneficial effects of subchronic RA administration in passive avoidance learning and memory in control rats as well as in a pharmacological model of cholinergic deficit which continue to expand the knowledge base in creating new treatment strategies for cognition deficits and dementia. Of course, further studies are warranted for clinical use of RA in the management of demented subjects.
Flávia Moreira Lima
Full Text Available There is growing evidence showing that bipolar disorder is associated with persistent cognitive deficits. However, the exact meaning and impact of cognitive deficits in bipolar disorder is still not entirely known, even though they have been associated with poor psychosocial functioning. This study aims to summarize cognitive and psychosocial functioning findings of remitted bipolar patients. We conducted an extensive Medline search of the published English literature for the period January 2000– March 2014 using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Our results showed that: (1 all mood states of bipolar disorder are associated with cognitive impairment. However, the euthymic state is associated with less impairment than the other states; (2 there is a strong association between clinical factors (i.e, duration of illness, number of episodes, residual mood symptoms, comorbidities and cognitive impairment in euthymic bipolar patients, although these factors do not account fully for these deficits; (3 cognitive deficits, in particular, verbal learning and executive dysfunctions may contribute to poor functioning. In conclusion, our review suggests that cognitive deficits are strongly associated with mood episodes; such deficits persist, in lower degree, during remission. Impairment on cognitive performance may explain, in part, poor long–term functioning in remitted bipolar patients. It highlights that psychosocial interventions in combination with pharmacotherapy should be considered to improve cognition and enhance the level of functioning. Therefore, studies assessing the efficacy of novel strategies focused on cognitive and functional status are an important area of future investigation in bipolar disorder.
Eagles, J M; Beattie, J A; Restall, D B; Rawlinson, F; Hagen, S; Ashcroft, G W
STUDY OBJECTIVE--To study the association between cognitive impairment and early death in elderly patients living in the community. DESIGN--Case-control study of 410 patients assessed by the mental status questionnaire and followed up after three years. SETTING--A general practice in Inverurie, Aberdeenshire, with 14,000 patients. PATIENTS--205 Patients aged greater than or equal to 65 with cognitive impairment according to the mental status questionnaire (score less than or equal to 8) and 205 patients scoring greater than 8 on the questionnaire matched for age and sex. MAIN OUTCOME MEASURE--Death. RESULTS--The relative risk of death in the cognitively impaired patients overall was 3.5. Those patients who scored less than or equal to 7 on the mental status questionnaire were five times more likely to die than their controls. There was no difference in risk of death between those with severe or moderate cognitive impairment. CONCLUSIONS--Cognitive impairment is associated with early death. PMID:2106935
Full Text Available Cognitive impairment due to cerebrovascular disease is termed "Vascular Cognitive Impairment" (VCI and forms a spectrum that includes Vascular Dementia (VaD and milder forms of cognitive impairment referred to as Vascular Mild Cognitive Impairment (VaMCI. VCI represents a complex neurological disorder that occurs as a result of interaction between vascular risk factors such as hypertension, diabetes, obesity, dyslipidemia, and brain parenchymal changes such as macro and micro infarcts, haemorrhages, white matter changes, and brain atrophy occurring in an ageing brain. Mixed degenerative and vascular pathologies are increasingly being recognised and an interaction between the AD pathology, vascular risk factors, and strokes is now proposed. The high cardiovascular disease burden in India, increasing stroke incidence, and ageing population have contributed to large numbers of patients with VCI in India. Inadequate resources coupled with low awareness make it a problem that needs urgent attention, it is important identify patients at early stages of cognitive impairment, to treat appropriately and prevent progression to frank dementia.
Full Text Available Abstract Background Cognitive impairment is a common feature in multiple sclerosis (MS patients and occurs in 60% of all cases. Unfortunately, neurological examination does not always agree with the neuropsychological evaluation in determining the cognitive profile of the patient. On the other hand, psychophysiological techniques such as event-related potentials (ERPs can help in evaluating cognitive impairment in different pathologies. Behavioural responses and EEG signals were recorded during the experiment in three experimental groups: 1 a relapsing-remitting group (RRMS, 2 a benign multiple sclerosis group (BMS and 3 a Control group. The paradigm employed was a spatial attention task with central cues (Posner experiment. The main aim was to observe the differences in the performance (behavioural variables and in the latency and amplitude of the ERP components among these groups. Results Our data indicate that both MS groups showed poorer task performance (longer reaction times and lower percentage of correct responses, a latency delay for the N1 and P300 component, and a different amplitude for the frontal N1. Moreover, the deficit in the BMS group, indexed by behavioural and pyschophysiological variables, was more pronounced compared to the RRMS group. Conclusion The present results suggest a cognitive impairment in the information processing in all of these patients. Comparing both pathological groups, cognitive impairment was more accentuated in the BMS group compared to the RMSS group. This suggests a silent deterioration of cognitive skills for the BMS that is not usually treated with pharmacological or neuropsychological therapy.
Vogel, A; Bhattacharya, S; Larsen, J L
This study examined the prevalence of cognitive impairment and its association with depressive symptoms and self-reported cognitive complaints in Danish outpatients with systemic lupus erythematosus (SLE). Fifty-seven consecutive female SLE-outpatients were examined with a comprehensive neuropsyc......This study examined the prevalence of cognitive impairment and its association with depressive symptoms and self-reported cognitive complaints in Danish outpatients with systemic lupus erythematosus (SLE). Fifty-seven consecutive female SLE-outpatients were examined with a comprehensive...
Fátima González Palau
Full Text Available Due to the significant increase in the percentage of older adults, as well as degenerative diseases, there is growing interest in the determination of effective psychosocial approaches aimed to subjects with mild cognitive impairment (MCI. Recent experimental studies indicate positive effects of cognitive interventions in population with DCL in both, traditional methods and computer based interventions. The present review provides a systematic analysis of the literature in order to assess the effect and scope of actual non-pharmacological cognitive interventions, aimed to older adults with mild cognitive impairment.
Pamela M Greenwood
Full Text Available What is the neurocognitive basis for the considerable individual differences observed in functioning of the adult mind and brain late in life? We review the evidence that in healthy old age the brain remains capable of both neuronal and cognitive plasticity, including in response to environmental and experiential factors. Neuronal plasticity (e.g. neurogenesis, synaptogenesis, cortical re-organization refers to neuron-level changes that can be stimulated by experience. Cognitive plasticity (e.g. increased dependence on executive function refers to adaptive changes in patterns of cognition related to brain activity. We hypothesize that successful cognitive aging requires interactions between these two forms of plasticity. Mechanisms of neural plasticity underpin cognitive plasticity and in turn, neural plasticity is stimulated by cognitive plasticity. We examine support for this hypothesis by considering evidence that neural plasticity is stimulated by learning and novelty and enhanced by both dietary manipulations (low-fat, dietary restriction and aerobic exercise. We also examine evidence that cognitive plasticity is affected by education and training. This is a testable hypothesis which could be assessed in humans in randomized trials comparing separate and combined effects of cognitive training, exercise, and diet on measures of cognitive and brain integrity. Greater understanding of the factors influencing the course of cognitive aging and of the mechanisms underlying those factors could provide information on which people could base choices that improve their ability to age successfully.
Monthakantirat, Orawan; Sukano, Wichitsak; Umehara, Kaoru; Noguchi, Hiroshi; Chulikhit, Yaowared; Matsumoto, Kinzo
Miroestrol (MR) is a phytoestrogen isolated from Pueraria candollei var. mirifica (KwaoKrueaKhao), a Thai medicinal plant used for rejuvenation. We examined the effects of MR on cognitive function, oxidative brain damage, and the expression of genes encoding brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element-binding protein (CREB), factors implicated in neurogenesis and synaptic plasticity, in ovariectomized (OVX) mice. OVX decreased serum 17β-estradiol level and uterine weight. OVX also impaired object recognition performance in the novel object recognition test and spatial cognitive performance in the Y-maze test and the water maze test. Daily treatment of MR dose-dependently attenuated OVX-induced cognitive dysfunction. Moreover, OVX mice had a significantly increased level of thiobarbituric acid-reactive substances, and down-regulated expression levels of BDNF and CREB mRNAs in the hippocampus and frontal cortex. MR treatment as well as hormone replacement therapy with 17β-estradiol significantly reversed these neurochemical alterations caused by OVX. These results suggest that MR ameliorates cognitive deficits in OVX animals via attenuation of OVX-induced oxidative stress and down-regulation of BDNF and CREB mRNA transcription in the brain. Our findings raise the possibility that MR and Pueraria candollei var. mirifica, the plant of origin of MR, may have a beneficial effect on cognitive deficits like AD in which menopause/ovariectomy are implicated as risk factors.
Masiran, Ruziana; Pang, Nicholas Tze Ping
We report a case of a man aged 67 years presenting with recent depressive symptoms and paranoid ideations in addition to 1-year cognitive impairment. He has vascular risk factors and family history of memory loss. An episode of depression 2 decades ago resolved spontaneously but was followed by occupational decline. On mental state examination, he denied having depressed mood, hallucinations or delusions, but there were prominent word-finding difficulties and impaired attention and concentration.
B. A. Abusueva; M. A. Evzel’man; P R Kamchatnov; Kh. Yu. Umarova
Background. Cognitive disorders may often lead to professional invalidisation and increasing dependence on the external assistance in every day life. Identification of patients with preserved intellectual status and social adaptation but with mild cognitive impairment (MCI) is considered to be an effective measure. MCI detection and timely initiation of treatment in most patients is essential to delay the onset of severe dementia.Objective. Investigating influence of Cellex in patients with c...
Federerico Filipin; Mónica Feldman; María Martelli; Viviana Sánchez; Virginia García; Graciela Tufro; Cecilia Serrano; Taragano,Fernando E.; Silvina Heisecke; Carol Dillon
Cognitive decline due to neurodegenerative diseases is a prevalent worldwide problem. Both pharmacological and non-pharmacological treatments to improve, delay or stop disease progression are of vital importance. Cognitive stimulation is frequently used in clinical practice; however, there are few studies that demonstrate its efficacy. Aim: To evaluate the efficacy of cognitive stimulation in patients with mild cognitive impairment (CDR = 0.5) and dementia (CDR = 1). Methods: A retrospective ...
Full Text Available The aim of this study was to investigate the effect of the cognitive impairment on functional status in patients with subacute stroke. Fifty-two patients with subacute stroke were included in the study. Mini mental state examination (MMSE test was used for the evaluation of cognitive status. Patients were separated into two groups according to their cognitive functions. Functional follow-up parameters were activities of daily living (ADL, global recovery and ambulation status. All patients were evaluated on admission to rehabilitation unit, at discharge and 6 months after discharge. Forty-four patients were completed the study. Mean age was 66 and 57 years; disease duration on admission was 4,8 and 3,5 months in the cognitively impaired and normal groups, respectively. Significant improvement was found in terms of functional follow-up parameters in both groups at discharge (<.05. Functional follow-up parameters did not show statistically significant difference between the groups. But community ambulation rate was higher in cognitively normal group at the sixth month visit. As a result of this study, inpatient rehabilitation was effective both cognitively normal and impaired subacute stroke patients.
Alvarez-Sabín, Jose; Román, Gustavo C
Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.
Vogel, Asmus; Hasselbalch, Steen G; Gade, Anders;
To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD).......To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD)....
Full Text Available Traumatic brain injury (TBI is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits.
Xiao, Weihua; Chen, Peijie; Liu, Xiaoguang; Zhao, Linlin
The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA) supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C) Control, E) Exercise, (E1) Exercise with one week to recover, (ES) Exercise + Supplementation and (ES1) Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031), reactive oxygen species (ROS) production (decreased by 26%, p = 0.003) and MHC II mRNA (decreased by 22%, p = 0.041) of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05). Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.
Full Text Available The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C Control, E Exercise, (E1 Exercise with one week to recover, (ES Exercise + Supplementation and (ES1 Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031, reactive oxygen species (ROS production (decreased by 26%, p = 0.003 and MHC II mRNA (decreased by 22%, p = 0.041 of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05. Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.
Full Text Available Recent studies showed that cyanobacteria-derived microcystin-leucine-arginine (MCLR can cause hippocampal pathological damage and trigger cognitive impairment; but the underlying mechanisms have not been well understood. The objective of the present study was to investigate the mechanism of MCLR-induced cognitive deficit; with a focus on endoplasmic reticulum (ER stress. The Morris water maze test and electrophysiological study demonstrated that MCLR caused spatial memory injury in male Wistar rats; which could be inhibited by ER stress blocker; tauroursodeoxycholic acid (TUDCA. Meanwhile; real-time polymerase chain reaction (real-time PCR and immunohistochemistry demonstrated that the expression level of the 78-kDa glucose-regulated protein (GRP78; C/EBP homologous protein (CHOP and caspase 12 were significantly up-regulated. These effects were rescued by co-administration of TUDCA. In agreement with this; we also observed that treatment of rats with TUDCA blocked the alterations in ER ultrastructure and apoptotic cell death in CA1 neurons from rats exposed to MCLR. Taken together; the present results suggested that ER stress plays an important role in potential memory impairments in rats treated with MCLR; and amelioration of ER stress may serve as a novel strategy to alleviate damaged cognitive function triggered by MCLR.
Full Text Available Background/Aim: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6-methylanthraquinone, which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. Methods: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg or saline (control. Emodin (4 mg/kg was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Results: Emodin significantly prevented the increase of leukocyte (n=8, Pin vivo prothrombotic effect of DEP in pial arterioles (n=6, Pin vitro in whole blood (n=4-5, PConclusion: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution.
Mao, Xueqin; Zhang, Ling; Xia, Qing; Sun, Zhaofeng; Zhao, Xiaomin; Cai, Hongxin; Yang, Xiaoda; Xia, Zuoli; Tang, Yujing
Vanadium compounds have been recognized for their hypoglycemic effects; however, potential short and long-term vanadium toxicity has slowed the acceptance for therapeutic use. In the present work, three batches of vanadium-enriched chickpea sprout (VCS) were prepared by incubating chickpea seeds in presence of 200, 100, and 50 microg/ml of sodium orthovanadate (SOV). The effects of oral administration of chickpea sprout (CS) and VCS food for 8 weeks on streptozotocin-induced (STZ) diabetic rats were investigated. Both CS and VCS food was found to ameliorate some hyperglycemic symptoms of the diabetic rats, i.e. improve lipid metabolism, decrease blood glucose level, prevent body weight loss, and reduce impairment of diabetic related spatial learning and memory. Serum insulin was substantially elevated in treated diabetic rats, which is probably one important reason for the hypoglycemic effect. Compared with CS alone, VCS100 food exhibited remarkably enhanced effectiveness in alleviating diabetes induced hyperglycemia and memory loss. Moreover, vanadium-enriched chickpeas appeared to abolish the vanadium induced toxicity associated with administration of this metal for diabetes during the 8-week study period. This study suggested further work of the vanadium speciation in CS and novel hypoglycemic mechanism for the antidiabetic activity of vanadium agents. Vanadium containing (VCS) food could be a dietary supplement for the diabetic status.
Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome…
Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.
Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…
Blieszner, Rosemary; Roberto, Karen A.
Purpose: We examined characteristics, responses, and psychological well-being of care partners who support and assist older adults recently diagnosed with mild cognitive impairment (MCI). Design and Methods: Based on a sample of 106 care partners of community residents diagnosed with MCI at memory clinics, we conducted face-to-face interviews…
Ebert, Kerry Danahy; Rentmeester-Disher, Jill; Kohnert, Kathryn
Substantial evidence points to the presence of subtle weaknesses in the nonlinguistic cognitive processing skills of children with primary (or specific) language impairment (PLI). It is possible that these weaknesses contribute to the language learning difficulties that characterize PLI, and that treating them can improve language skills. To test…
Changhao Yin; Siou Li; Weina Zhao; Jiachun Feng
The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.
van Rossum, M. E.; Koek, H. L.
Objective Knowledge about factors predicting functional disability in mild cognitive impairment (MCI) and dementia would help health care providers to identify those patients who are at high risk of functional disability. Previous research is scarce and focused on only a small number of possible pre
Balietti, Marta; Giuli, Cinzia; Fattoretti, Patrizia; Fabbietti, Paolo; Postacchini, Demetrio; Conti, Fiorenzo
We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A.
Full Text Available Aims: This study aimed to identify differences in the implementation of cognitive activities and instrumental activities of daily living (IADLs between healthy individuals and subjects with mild cognitive impairment (MCI. Methods: The study included 2,498 cognitively healthy subjects (mean age, 71.2 ± 5.1 years and 809 MCI subjects (mean age, 71.8 ± 5.4 years. The subjects were interviewed regarding their participation in cognitive activities and the implementation of IADLs. Results: We found a significant association between participation in any cognitive activities (p Conclusions: Our study revealed that greater participation in cognitive activity was associated with lower odds of MCI. Participation in cognitive activities may reflect differences between healthy and MCI subjects. To clarify the causal relationship between cognitive activities and MCI, further studies are required.
Cancer patients often suffer from various distresses, including cognitive impairment. Cognitive impairment during and after cancer diagnosis and treatment are collectively called "Cancer-related cognitive impairment (CRCI)". The number of publications about cognitive impairment due to cancer therapy, especially chemotherapy, hormonal therapy, and radiotherapy, has been growing. Patients often worry not only about their disease condition and therapies, but also experience concerns regarding their memory, attention, and ability to concentrate. Even subtle CRCI can have a significant impact on social relationships, the ability to work, undergo treatment, accomplish meaningful goals, and the quality of life. Longitudinal studies of cancer patients indicated that up to 75% experience CRCI during treatment. Furthermore, CRCI may persist for many years following treatment. However, it is not well understood by most physicians and medical staff. CRCI can be mediated through increased inflammatory cytokines and hormonal changes. In addition, the biology of the cancer, stress, and attentional fatigue can also contribute to CRCI. Genetic factors and co-occurring symptoms may explain some of the inter-individual variability in CRCI. Researchers and patients are actively trying to identify effective interventional methods and useful coping strategies. Many patients are willing to discuss their disease condition and future treatment with medical staff and/or their families. Some patients also hope to discuss their end-of-life care. However, it is difficult to express their will after developing cognitive impairment. Advance care planning (ACP) can help in such situations. This process involves discussion between a patient, their family, and clinicians to clarify and reflect on values, treatment preferences, and goals to develop a shared understanding of how end-of-life care should proceed. The number of cancer patients with cognitive impairment has been increasing owing to the
Russell, Gregor; Burns, Alistair
ABSTRACT Background: Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is common in conditions causing significant visual impairment. Many authors advise reassurance, considering the condition benign. However, others have suggested that CBS may in some patients represent the early stages of dementia. This review seeks to systematically examine the evidence for any link between CBS and cognitive impairment. Methods: Literature search using OVID Medline, PsychINFO, and Embase. Results: Three studies where cognitive functioning was the primary focus of the research were found. All were small, did not properly apply diagnostic criteria, and reported conflicting results. Eight other studies commented on cognitive functioning, but none used tests sufficiently sensitive to detect changes seen in early dementia. One hundred and thirty four case reports were scrutinized, and reports found of 16 patients with CBS where dementia emerged. High rates of partial insight at diagnosis of CBS were seen in these patients. Conclusions: There have been no adequately powered studies, using accepted diagnostic criteria, where changes in cognitive functioning were the primary outcome. Existing studies are of limited methodological quality and allow no conclusion regarding a relationship between cognitive impairment and CBS to be reached. Numerous case reports of dementia developing in patients with CBS and partial insight raise the possibility of a link between these conditions. There is a clear need for properly constructed studies to investigate this.
Full Text Available ABSTRACT One in six patients admitted for stroke was previously demented. These patients have less access to appropriate stroke care, although little is known about their optimal management. Objective To determine how pre-stroke cognitive impairment can be detected, its mechanism, and influence on outcome and management. Methods Literature search. Results (i A systematic approach with the Informant Questionnaire of Cognitive Decline in the Elderly is recommended; (ii Pre-stroke cognitive impairment may be due to brain lesions of vascular, degenerative, or mixed origin; (iii Patients with pre-stroke dementia, have worse outcomes, more seizures, delirium, and depression, and higher mortality rates; they often need to be institutionalised after their stroke; (iv Although the safety profile of treatment is not as good as that of cognitively normal patients, the risk:benefit ratio is in favour of treating these patients like others. Conclusion Patients with cognitive impairment who develop a stroke have worse outcomes, but should be treated like others.
Full Text Available Muhammed Emin Özcan,1 Bahri İnce,2 Ayhan Bingöl,3 Simge Ertürk,3 Meriç Adil Altınöz,4 Hasan Hüseyin Karadeli,1 Abdulkadir Koçer,5 Talip Asil1 1Deparment of Neurology, Medical Faculty, Bezmialem Vakif University, Istanbul, Turkey; 2Department of Psychiatry, Bakirköy Research and Training Hospital for Psychiatry, Istanbul, Turkey; 3Mayis Psychology Center, Istanbul, Turkey; 4Department of Molecular Biology and Genetics, Haliç University, Istanbul, Turkey; 5Department of Neurology, Medical Faculty, İstanbul Medeniyet University, Göztepe, Istanbul, Turkey Purpose: Although smoking is known to cause various symptoms in multiple sclerosis (MS patients, there have been no reports regarding the relationship between smoking and cognitive impairment in MS. Studying the effects of cigarette smoking in MS patients is imperative as there is a high prevalence of cognitive impairment in MS patients. In this study we examined the potentially deleterious effects of heavy smoking on mentation of patients with MS. Patients and methods: MS patients receiving care at the Neurology Clinic at Bezmialem Vakif University, between the ages of 18–65 years who have at least graduated elementary school were included in the study. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N is a commonly used method to assess cognitive function in MS patients and was utilized in our study. Patients that smoked for at least 10 pack-years were considered heavy smokers.Results: All the patients were stratified into two groups: heavy smokers (n=20 and nonsmokers (n=24. For heavy smokers, their cognitive functioning was more impaired than that of nonsmokers (P=0.04, χ2=4.227. For patients with cognitive impairment, 78.9% of the Paced Auditory Serial Addition Test and 63.2% of the Symbol Digit Modalities Test scores were found to be lower.Conclusion: Previous reports have suggested that smoking increases the frequency of relapse among individuals with
Full Text Available Intraindividual variability among cognitive domains may predict dementia independently of interindividual differences in cognition. A multidomain cognitive battery was administered to 2305 older adult women (mean age 74 years enrolled in an ancillary study of the Women’s Health Initiative. Women were evaluated annually for probable dementia and mild cognitive impairment (MCI for an average of 5.3 years using a standardized protocol. Proportional hazards regression showed that lower baseline domain-specific cognitive scores significantly predicted MCI (N=74, probable dementia (N=45, and MCI or probable dementia combined (N=101 and that verbal and figural memory predicted each outcome independently of all other cognitive domains. The baseline intraindividual standard deviation across test scores (IAV Cognitive Domains significantly predicted probable dementia and this effect was attenuated by interindividual differences in verbal episodic memory. Slope increases in IAV Cognitive Domains across measurement occasions (IAV Time explained additional risk for MCI and MCI or probable dementia, beyond that accounted for by interindividual differences in multiple cognitive measures, but risk for probable dementia was attenuated by mean decreases in verbal episodic memory slope. These findings demonstrate that within-person variability across cognitive domains both at baseline and longitudinally independently accounts for risk of cognitive impairment and dementia in support of the predictive utility of within-person variability.
Full Text Available Mild cognitive impairment (MCI can be the initial manifestation of autoimmune limbic encephalitis (ALE, a disorder that at times presents a diagnostic challenge. In addition to memory impairment, clinical features that might suggest this disorder include personality changes, agitation, insomnia, alterations of consciousness, and seizures. Once recognized, ALE typically responds to treatment with immune therapies, but long-term cognitive deficits may remain. We report two cases of patients with MCI who were ultimately diagnosed with ALE with antibodies against the voltage gated potassium channel complex. Months after apparent resolution of their encephalitides, both underwent neuropsychological testing, which demonstrated persistent cognitive deficits, primarily in the domains of memory and executive function, for cases 1 and 2, respectively. A brief review of the literature is included.
Verdelho, Ana; Madureira, Sofia; Ferro, José M
BACKGROUND AND PURPOSE: We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. METHODS: The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates...... the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria....... Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. RESULTS: Six hundred thirty-nine subjects were included (74.1±5 years old, 55% women, 9.6±3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia...
Sambati, Luisa; Calandra-Buonaura, Giovanna; Poda, Roberto; Guaraldi, Pietro; Cortelli, Pietro
Many studies have addressed the relation between orthostatic hypotension (OH) and cognitive impairment (CI) in the elderly, in mild cognitive impairment, vascular and neurodegenerative dementias and movement disorders, such as Parkinson's disease. However, results concerning both the increased coexistence of the two conditions and their causal relationship remain controversial. According to the literature three hypotheses can be formulated on the relation between OH and CI. In neurodegenerative disease, OH and CI may result from a common pathological process which affects areas involved in both cognition and cardiovascular autonomic control. Alternatively, OH may lead to cerebral hypoperfusion which is supposed to play a role in the development of CI. Finally, recent data suggest that CI should probably be considered more a transient symptom of OH than a chronic effect. This study reviews the literature reports on the relationship between OH and CI, and emphasises the need for longitudinal studies designed to investigate this topic.
Full Text Available Aims: To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ-induced diabetic rats and to explore the mechanisms of that phenomenon. Methods: Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15, Res group (normal Sprague Dawley rats treated with resveratrol, n = 15, diabetes mellitus group (DM group, n = 15 and DM + Res group (diabetic rats treat with resveratrol, n = 15. Streptozotocin (STZ was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor and BDNF (Brain Derived Neurotrophic Factor via western blotting analysis. Results: Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression. Conclusions: Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.
Joubert, Sven; Brambati, Simona M.; Ansado, Jennyfer; Barbeau, Emmanuel J.; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Celine; Kergoat, Marie-Jeanne
Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to…
Liu, Qing; Zhu, Zude; Teipel, Stefan J.; Yang, Jianwei; Xing, Yi; Tang, Yi; Jia, Jianping
Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders. PMID:28289381
Saggu, Raman; Schumacher, Toni; Gerich, Florian; Rakers, Cordula; Tai, Khalid; Delekate, Andrea; Petzold, Gabor C
Vascular cognitive impairment is the second most common form of dementia. The pathogenic pathways leading to vascular cognitive impairment remain unclear but clinical and experimental data have shown that chronic reactive astrogliosis occurs within white matter lesions, indicating that a sustained pro-inflammatory environment affecting the white matter may contribute towards disease progression. To model vascular cognitive impairment, we induced prolonged mild cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia within white matter tracts, demyelination and axonal degeneration, consecutive spatial memory deficits, and loss of white matter integrity, as measured by ultra high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis was accompanied by activation of the pro-inflammatory transcription factor nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant negative inhibitor of NF-kB under the control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter (GFAP-IkBα-dn), we found that transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and axonal loss, maintained white matter structural integrity, and preserved memory function. Collectively, our results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.
Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen
Approximately five million people suffer with Alzheimer's disease (AD) and more than twenty-four million people are diagnosed with AD, pre-senile dementia, and other disorders of cognitive loss worldwide. Furthermore, the annual cost per patient with AD can approach $200,000 with an annual population aggregate cost of $100 billion. Yet, complete therapeutic prevention or reversal of neurovascular injury during AD and cognitive loss is not achievable despite the current understanding of the cellular pathways that modulate nervous system injury during these disorders. As a result, identification of novel therapeutic targets for the treatment of neurovascular injury would be extremely beneficial to reduce or eliminate disability from diseases that lead to cognitive loss or impairment. Here we describe the capacity of intrinsic cellular mechanisms for the novel pathways of erythropoietin and forkhead transcription factors that may offer not only new strategies for disorders such as AD and cognitive loss, but also function as biomarkers for disease onset and progression.
Ebert, Kerry Danahy; Rentmeester-Disher, Jill; Kohnert, Kathryn
Substantial evidence points to the presence of subtle weaknesses in the nonlinguistic cognitive processing skills of children with primary (or specific) language impairment (PLI). It is possible that these weaknesses contribute to the language learning difficulties that characterize PLI, and that treating them can improve language skills. To test this premise, we treated two nonlinguistic cognitive processing skills, processing speed and sustained selective attention, in two Spanish-English bilingual children with PLI. The study followed a single-subject multiple baseline design, with both repeated measures and standardized pre- and post-testing as outcome measures. Results from the repeated measures tasks showed that both participants made gains in nonlinguistic cognitive processing skills as well as in Spanish and English. These results both replicate and extend prior work showing that nonlinguistic cognitive processing treatment can positively affect language skills in children with PLI.
George A Heckman
Full Text Available George A Heckman, Christopher J Patterson, Catherine Demers, Joye St.Onge, Irene D Turpie, Robert S McKelvieDepartment of Medicine, McMaster University, Hamilton, Ontario, CanadaAbstract: As populations age, heart failure (HF is becoming increasingly common, and in addition to a high burden of morbidity and mortality, HF has an enormous financial impact. Though disproportionately affected by HF, the elderly are less likely to receive recommended therapies, in part because clinical trials of HF therapy have ignored outcomes of importance to this population, including impaired cognitive function (ICF. HF is associated with ICF, manifested primarily as delirium in hospitalized patients, or as mild cognitive impairment or dementia in otherwise stable outpatients. This association is likely the result of shared risk factors, as well as perfusion and rheological abnormalities that occur in patients with HF. Evidence suggests that these abnormalities may be partially reversible with standard HF therapy. The clinical consequences of ICF in HF patients are significant. Clinicians should consider becoming familiar with screening instruments for ICF, including delirium and dementia, in order to identify patients at risk of nonadherence to HF therapy and related adverse consequences. Preliminary evidence suggests that optimal HF therapy in elderly patients may preserve or even improve cognitive function, though the impact on related outcomes remains to be determined.Keywords: heart failure, mild cognitive impairment, delirium, dementia, elderly
Full Text Available BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks.
Bücker, Joana; Kapczinski, Flavio; Post, Robert; Ceresér, Keila M; Szobot, Claudia; Yatham, Lakshmi N; Kapczinski, Natalia S; Kauer-Sant'Anna, Márcia
Exposure to traumatic events during childhood is often associated with the development of psychiatric disorders, cognitive impairment, and poor functioning in adulthood. However, few studies have examined cognitive function, including executive function, memory, and attention, in school-aged children with early trauma compared with age- and sex-matched controls. We recruited 30 medication-naive children between 5 and 12 years of age with a history of early severe trauma from a foster care home, along with 30 age- and sex-matched controls. Psychiatric diagnoses were based on Kiddie Schedule for Affective Disorders and Schizophrenia Epidemiologic Version (K-SADS-E) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and were confirmed with a clinical interview. The neuropsychologic battery was tailored to assess broad cognitive domains such as learning/working memory, executive function, attention, verbal/premorbid intellectual functioning, and impulsivity. There was a higher prevalence of subsyndromal symptoms in children with a history of childhood trauma, although they rarely met all of the diagnostic criteria for a disorder. Moreover, lower estimated intellectual functioning scores were associated with subsyndromal symptoms in children with a history of trauma, and they performed more poorly on the Digits Span Test of the Wechsler Intelligence Scale for Children-III Edition, suggesting attention impairment. There is a high prevalence of subsyndromal symptoms in school-aged children with trauma and an attention impairment, which may contribute to a cumulative deficit early in cognitive development. These findings further support the need for early interventions that can prevent cognitive impairment when childhood trauma occurs.
Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin
Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789
Wilson, M-M G; Morley, J E
Dehydration is a reliable predictor of impaired cognitive status. Objective data, using tests of cortical function, support the deterioration of mental performance in mildly dehydrated younger adults. Dehydration frequently results in delirium as a manifestation of cognitive dysfunction. Although, the occurrence of delirium suggests transient acute global cerebral dysfunction, cognitive impairment may not be completely reversible. Animal studies have identified neuronal mitochondrial damage and glutamate hypertransmission in dehydrated rats. Additional studies have identified an increase in cerebral nicotinamide adenine dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with dehydration. Available evidence also implicates NOS as a neurotransmitter in long-term potentiation, rendering this a critical enzyme in facilitating learning and memory. With ageing, a reduction of NOS activity has been identified in the cortex and striatum of rats. The reduction of NOs synthase activity that occurs with ageing may blunt the rise that occurs with dehydration, and possibly interfere with memory processing and cognitive function. Dehydration has been shown to be a reliable predictor of increasing frailty, deteriorating mental performance and poor quality of life. Intervention models directed toward improving outcomes in dehydration must incorporate strategies to enhance prompt recognition of cognitive dysfunction.
Rise, Ida Vikan; Haro, Josep Maria; Gjervan, Bjørn
Introduction Data specific to late-life bipolar disorder (BD) are limited. Current research is sparse and present guidelines are not adapted to this group of patients. Objectives We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late-life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment. Methods Eligible studies were identified in MedLine by the Medical Subject Headings terms “bipolar disorder” and “aged”. We only included original research reports published in English between 2012 and 2015. Results From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age-matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested. Conclusion There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that this group needs an adapted clinical assessment and specific clinical guidelines need to be established. PMID:27274256
In this review, the immune-to-brain communication pathways are briefly summarized, with emphasis on the impact of immune cells and their mediators on learning, memory and other cognitive domains. Further, the acute response of the central nervous system to peripherally generated inflammatory stimuli - termed as sickness behaviour - is described, and the central role of microglia in this immune-to-brain crosstalk in physiological and pathological conditions is highlighted. Finally, the role and consequences of immunological processes related to cognitive impairment in multiple sclerosis are discussed.
Balsamo, Sandor; Willardson, Jeffrey M; Frederico, Santos de Santana; Prestes, Jonato; Balsamo, Denise Coscrato; Dahan, da Cunha Nascimento; Dos Santos-Neto, Leopoldo; Nobrega, Otávio T
Physical activity has a protective effect on brain function in older people. Here, we briefly reviewed the studies and results related to the effects of exercise on cognitive impairment and Alzheimer's disease. The main findings from the current body of literature indicate positive evidence for structured physical activity (cardiorespiratory and resistance exercise) as a promising non-pharmacological intervention for preventing cognitive decline. More studies are needed to determine the mechanisms involved in this preventative effect, including on strength, cardiorespiratory, and other types of exercise. Thus, the prevention of Alzheimer's disease may depend on healthy lifestyle habits, such as a structured physical fitness program.
Hansen, Jens Peter; Østergaard, Birte; Nordentoft, Merete
Background Between 75% and 85% of patients with schizophrenia have cognitive impairments. The impairments have a negative influence on the patient's ability to maintain work, maintain contact with friends, independent living and living in a social relationship. Compared to treatment as usual......, studies using Cognitive Adaptation Training (CAT), including training of compensatory strategies to sequence patient's adaptive behaviours, have shown improvement in social functioning, decreased relapse, better compliance to medical treatment and increased quality of life. However, no studies, up to now......, have investigated the effect of CAT in younger patients with schizophrenia Purpose The purpose of this study is to evaluate the effect of CAT in comparison with treatment as usual, focusing on social functions, symptoms, relapse, re-hospitalisation, and quality of life in younger outpatients...
Hansen, Jens Peter; Østergaard, Birte; Nordentoft, Merete
Background Bewteen 75% and 85% of patients with schizophrenia have cognitive impairments. The impairments have a negative influence on the patient's ability to maintain work, maintain contact with friends, independent living and living in a social relationship. Compared to treatment as usual......, studies using Cognitive Adaptation Training (CAT), including training of compensatory strategies to sequence patient's adaptive behaviours, have shown improvement in social functioning, decreased relapse, better compliance to medical treatment and increased quality of life. However, no studies, up to now......, have investigated the effect of CAT in younger patients with schizophrenia Purpose The purpose of this study is to evaluate the effect of CAT in comparison with treatment as usual, focusing on social functions, symptoms, relapse, re-hospitalisation, and quality of life in younger outpatients...
Elder, Gregory A
Traumatic brain injury (TBI) is a common cause of morbidity and mortality in military life. Interest in military TBI has increased recently due to the conflicts in Iraq and Afghanistan. Certain types of TBI are relatively unique to the military, the most prominent being blast-related TBI. Blast-related mild TBI has been of particular concern in veterans from the most recent conflicts although controversy remains concerning its separation from post-traumatic stress disorder. TBI is also a risk factor for the later development of neurodegenerative diseases in which cognitive impairment is prominent putting veterans at risk for disorders including Alzheimer's disease and chronic traumatic encephalopathy. Recent evidence associating TBI with chronic cognitive impairment is reviewed in the context of its relevance to military veterans.
Cameron J. Dunn
Full Text Available Amnestic mild cognitive impairment (aMCI is believed to represent a transitional stage between normal healthy ageing and the development of dementia. In particular, aMCI patients have been shown to have higher annual transition rates to Alzheimer's Disease (AD than individuals without cognitive impairment. Despite intensifying interest investigating the neuroanatomical basis of this transition, there remain a number of questions regarding the pathophysiological process underlying aMCI itself. A number of recent studies in aMCI have shown specific impairments in connectivity within the default mode network (DMN, which is a group of regions strongly related to episodic memory capacities. However to date, no study has investigated the integrity of the DMN between patients with aMCI and those with a non-amnestic pattern of MCI (naMCI, who have cognitive impairment, but intact memory storage systems. In this study, we contrasted the DMN connectivity in 24 aMCI and 33 naMCI patients using seed-based resting state fMRI. The two groups showed no statistical difference in their DMN intra-connectivity. However when connectivity was analysed according to performance on measures of episodic memory retrieval, the two groups were separable, with aMCI patients demonstrating impaired functional connectivity between the hippocampal formation and the posterior cingulate cortex. We provide evidence that this lack of connectivity is driven by impaired communication from the posterior cingulate hub and does not simply represent hippocampal atrophy, suggesting that posterior cingulate degeneration is the driving force behind impaired DMN connectivity in aMCI.
Dunn, Cameron J.; Duffy, Shantel L; Hickie, Ian B; Lagopoulos, Jim; Lewis, Simon J.G.; Naismith, Sharon L.; Shine, James M.
Amnestic mild cognitive impairment (aMCI) is believed to represent a transitional stage between normal healthy ageing and the development of dementia. In particular, aMCI patients have been shown to have higher annual transition rates to Alzheimer's Disease (AD) than individuals without cognitive impairment. Despite intensifying interest investigating the neuroanatomical basis of this transition, there remain a number of questions regarding the pathophysiological process underlying aMCI itself. A number of recent studies in aMCI have shown specific impairments in connectivity within the default mode network (DMN), which is a group of regions strongly related to episodic memory capacities. However to date, no study has investigated the integrity of the DMN between patients with aMCI and those with a non-amnestic pattern of MCI (naMCI), who have cognitive impairment, but intact memory storage systems. In this study, we contrasted the DMN connectivity in 24 aMCI and 33 naMCI patients using seed-based resting state fMRI. The two groups showed no statistical difference in their DMN intra-connectivity. However when connectivity was analysed according to performance on measures of episodic memory retrieval, the two groups were separable, with aMCI patients demonstrating impaired functional connectivity between the hippocampal formation and the posterior cingulate cortex. We provide evidence that this lack of connectivity is driven by impaired communication from the posterior cingulate hub and does not simply represent hippocampal atrophy, suggesting that posterior cingulate degeneration is the driving force behind impaired DMN connectivity in aMCI. PMID:24634833
Hugo, Julie; Ganguli, Mary
Synopsis Clinicians can diagnose the syndromes of dementia (major neurocognitive disorder) and mild cognitive impairment (mild neurocognitive disorder) based on history, examination, and appropriate objective assessments, using standard criteria such as DSM-5. They can then diagnose the etiological subtypes of these syndromes using standard criteria for each of them. Brain imaging and biomarkers are gaining ground for the differential diagnoses among the different disorders. Treatments for the most part are still symptomatic. PMID:25037289
Full Text Available Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg at one of three neurodevelopmental time periods [gestation days (GD 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND 60] and included: prepulse inhibition (PPI, latent inhibition (LI and delayed non-matching to sample (DNMTS. Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously were administered, and animals were re-tested in the same tasks (PND 110. Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11 resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI and selective (LI improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI and induced a global enhancement of sensorimotor gating (PPI.
G. R. Tabeeva
Full Text Available Aging is a physiological process that may develop long without manifestations of comorbidities. In the meantime a high proportion of elderly people very often experience limitations in daily life due to impairments in memory and other cognitive functions. Non-cognitive neuropsychiatric disorders, most commonly stress-related anxiety disorders, are a major contribution to maladaptation in these patients. The present studies of the neurobiology of aging enable one to decipher not only the mechanisms that underlie the physiology of brain aging, but also the factors that influence cognitive aging and aggravate the manifestations of cognitive dysfunction and neurodegenerative disease. The process of brain aging is known to presume the long-term preservation of functional neuroplasticity that is greatly influenced by different lifestyle factors, such as daily social and physical activities, the pattern and amount of food taken, cognitive activity, and stressful life events. These lifestyle factors are supposedly a potent tool to maintain physiological brain aging and a delayed cognitive diminution in elderly people. At the same time, studies of the possibility of pharmacologically correcting age-related (both cognitive and non-cognitive impairments are promising to improve everyday function in elderly people.
Deng, Shining; Li, Wei-Guang; Ding, Jing; Wu, Jinlin; Zhang, Yuanyuan; Li, Fei; Shen, Xiaoming
Developmental coordination disorder (DCD), a neurodevelopmental disability in which a child's motor coordination difficulties significantly interfere with activities of daily life or academic achievement, together with additional symptoms of diseases with childhood sensorimotor impairments, increases the risk of many cognitive problems. This exhibits the dynamic interplay between sensorimotor and cognition systems. However, the brain structures and pathways involved have remained unknown over the past decades. Here, we review developments in recent years that elucidate the neural mechanisms involved in the sensorimotor-cognitive difficulties. First, we briefly address the clinical and epidemiological discoveries in DCD as well as its comorbidities. Subsequently, we group the growing evidence including our findings that support the notion that sensorimotor manipulation indeed affects the cognition development at systematic, circuitry, cellular, and molecular levels. This corresponds to changes in diverse brain regions, synaptic plasticity, and neurotransmitter and receptor activity during development under these effects. Finally, we address the treatment potentials of task-oriented sensorimotor enhancement, as a new therapeutic strategy for cognitive rehabilitation, based on our current understanding of the neurobiology of cognitive-sensorimotor interaction.
Indra F. Willers
Full Text Available Abstract Mild cognitive impairment (MCI is the transitional stage between normal aging and Alzheimer's disease (AD. Impairments in semantic memory have been demonstrated to be a critical factor in early AD. The Boston Naming Test (BNT is a straightforward method of examining semantic or visuo-perceptual processing and therefore represents a potential diagnostic tool. The objective of this study was to examine naming ability and identify error types in patients with amnestic mild cognitive impairment (aMCI. Methods: Twenty aMCI patients, twenty AD patients and twenty-one normal controls, matched by age, sex and education level were evaluated. As part of a further neuropsychological evaluation, all subjects performed the BNT. A comprehensive classification of error types was devised in order to compare performance and ascertain semantic or perceptual origin of errors. Results: AD patients obtained significantly lower total scores on the BNT than aMCI patients and controls. aMCI patients did not obtain significant differences in total scores, but showed significantly higher semantic errors compared to controls. Conclusion: This study reveals that semantic processing is impaired during confrontation naming in aMCI.
Full Text Available Obstructive Sleep Apnea Syndrome (OSAS is a sleep disorder characterised by repetitive episodes of upper airway obstruction (apnea or reduced airflow (hypopnoea despite persistent respiratory effort. Apnea is defined as the cessation of breathing for at least 10 seconds during sleep, while hypopnoea is defined as at least 30% reduction in airflow for 10 seconds associated with oxygen desaturation and sleep fragmentation. The presence in the general population is about 4%. The principal symptoms are: excessive daytime sleepiness (EDS, snoring, dry throat, morning headache, night sweats, gastro-esophageal reflux, and increased blood pressure.Long term complications can be: increased cardio-cerebrovascular risk and cognitive impairment such as deficiency in attention, vigilance, visual abilities, thought, speech, perception and short term memory.Continuous Positive Airway Pressure (CPAP is currently the best non-invasive therapy for OSAS.CPAP guarantees the opening of upper airways using pulmonary reflexive mechanisms increasing lung volume during exhalation and resistance reduction, decreasing electromyografical muscular activity around airways.The causes of cognitive impairments and their possible reversibility after CPAP treatment have been analysed in numerous studies. The findings, albeit controversial, show that memory, attention and executive functions are the most compromised cognitive functions.The necessity of increasing the patient compliance with ventilotherapy is evident, in order to prevent cognitive deterioration and, when possible, rehabilitate the compromised functions, a difficult task for executive functions.
Lugnegård, Tove; Unenge Hallerbäck, Maria; Hjärthag, Fredrik; Gillberg, Christopher
Social cognition impairments are well described in both autism spectrum disorders, including Asperger syndrome (AS), and in schizophrenia spectrum disorders. However, little is known about whether there are differences between the two groups of disorders regarding this ability. The aim of this study was to compare social cognition abilities in AS and schizophrenia. Fifty-three individuals (26 men, 27 women) with a clinical diagnosis of AS, 36 (22 men, 14 women) with a clinical diagnosis of schizophrenic psychosis, and 50 non-clinical controls (19 men, 31 women) participated in the study. Clinical diagnoses were confirmed either by Structured Clinical Interview on DSM-IV diagnosis or the Diagnostic Interview for Social and Communication Disorders. Verbal ability was assessed using the Vocabulary subtest of the WAIS-III. Two social cognition instruments were used: Reading the Mind in the Eyes Test (Eyes Test) and the Animations Task. On the Eyes Test, patients with schizophrenia showed poorer results compared to non-clinical controls; however, no other group differences were seen. Both clinical groups scored significantly lower than the comparison group on the Animations Task. The AS group performed somewhat better than the schizophrenia group. Some differences were accounted for by gender effects. Implicit social cognition impairments appear to be at least as severe in schizophrenia as they are in AS. Possible gender differences have to be taken into account in future research on this topic.
Myotonic dystrophy type 1 (DM 1) is a heritable, multisystem disease that affects not only the muscles but also the brain. DM 1 is often accompanied by developmental behavioral disorders, such as autism spectrum disorders. The autistic traits in DM 1 may be related to social cognitive dysfunction. The social cognitive function of patients with DM 1 was examined with respect to facial emotion recognition and theory of mind, which is the specific cognitive ability to understand the mental states of other people. With respect to facial emotion recognition, the sensitivities to disgust and anger were lower among patients with DM 1 than among healthy subjects, and this difference could not be attributed to visual impairment. To examine the theory of mind ability, the "Reading the Mind in the Eyes" test and the faux pas recognition test were used. Patients with DM 1 were found to be impaired in both tests, but the results were not attributed to visual ability and lexical comprehension. The possible causes of social cognitive dysfunction in DM 1 are the l cerebral atrophy and white matter abnormalities in the temporal, frontal, and insular cortex. Dysfunctions in these areas may affect the emotional and theory of mind abilities in DM 1, which result in the behavioral and communication disorders.
Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T
There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.
Jonsdottir, I H; Nordlund, A; Ellbin, S; Ljung, T; Glise, K; Währborg, P; Wallin, A
Patients who seek medical care for stress-related mental health problems frequently report cognitive impairments as the most pronounced symptom. The purpose of the present study was to compare cognitive function in patients with stress-related exhaustion with that in healthy controls, using a comprehensive battery of cognitive tests. We also explored whether neuropsychological findings were related to severity of illness measured using the Shirom-Melamed burnout questionnaire and hospital anxiety and depression scale. Thirty-three patients (15 males) and 37 healthy controls (11 males), mean age 46 years [standard deviation (SD) 3.9] and 47 years (SD 4.3), respectively, were included in the final analysis. Five cognitive domains were assessed: (1) speed, attention and working memory, (2) learning and episodic memory, (3) executive functions, (4) visuospatial functions and (5) language. The most pronounced difference between patients and controls was seen on executive function, when tested with a multidimensional test, including aspects of speed, control and working memory. The patients also performed poorer on Digit span, measuring attention span and working memory as well as on learning and episodic memory, when measured as delayed recall and the difference between immediate and delayed recall. Delayed recall was the only test that was significantly related to severity of burnout symptoms among the patients. This could reflect poor cognitive sustainability in the patients with the highest burnout scores, as this particular test was the last one performed during the test session. This study clearly shows that cognitive impairment should be considered when evaluating and treating patients who seek medical care for stress-related exhaustion.
Full Text Available Background: Within the next 30 years, the number of visits older adults will make to emergency departments (EDs is expected to double from 16 million, or 14% of all visits, to 34 million and comprise nearly a quarter of all visits.Objective: The objectives of this study were to determine prevalence rates of cognitive impairment among older adults in the ED and to identify associations, if any, between environmental factors unique to the ED and rates of cognitive impairment.Methods: A cross-sectional observational study of adults 65 and older admitted to the ED of a large, urban, tertiary academic health center was conducted between September 2007 and May 2008. Patients were screened for cognitive impairment in orientation, recall and executive function using the Six-Item Screen (SIS and the CLOX1, clock drawing task. Cognitive impairment among this ED population was assessed and both patient demographics and ED characteristics (crowding, triage time, location of assessment, triage class were compared through adjusted generalized linear models.Results: Forty-two percent (350/829 of elderly patients presented with deficits in orientation and recall as assessed by the SIS. An additional 36% of elderly patients with no impairment in orientation or recall had deficits in executive function as assessed by the CLOX1. In full model adjusted analyses patients were more likely to screen deficits in orientation and recall (SIS if they were 85 years or older (Relative Risk [RR]=1.63, 95% Confidence Interval [95% CI]=1.3-2.07, black (RR=1.85, 95% CI=1.5-2.4 and male (RR=1.42, 95% CI=1.2-1.7. Only age was significantly associated with executive functioning deficits in the ED screened using the clock drawing task (CLOX1 (75-84 years: RR=1.35, 95% CI= 1.2-1.6; 85+ years: RR=1.69, 95% CI= 1.5-2.0.Conclusion: These findings have several implications for patients seen in the ED. The SIS coupled with a clock drawing task (CLOX1 provide a rapid and simple method for
Full Text Available Severe asymptomatic stenosis of the internal carotid artery (ICA leads to increased incidence of mild cognitive impairment (MCI likely through silent embolic infarcts and/or chronic hypoperfusion, but the brain dysfunction is poorly understood and difficult to diagnose. Thirty cognitively intact subjects with asymptomatic, severe (≥ 70%, unilateral stenosis of the ICA were compared with 30 healthy controls, matched for age, sex, cardiovascular risk factors and education level, on a battery of neuropsychiatric tests, voxel-based morphometry of magnetic resonance imaging (MRI, diffusion tensor imaging and brain-wise, seed-based analysis of resting-state functional MRI. Multivariate regression models and multivariate pattern classification (support vector machines were computed to assess the relationship between connectivity measures and neurocognitive performance. The patients had worse dizziness scores and poorer verbal memory, executive function and complex visuo-spatial performance than controls. Twelve out of the 30 patients (40% were considered to have MCI. Nonetheless, the leukoaraiosis Sheltens scores, hippocampal and brain volumes were not different between groups. Their whole-brain mean fractional anisotropy (FA was significantly reduced and regional functional connectivity (Fc was significantly impaired in the dorsal attention network (DAN, frontoparietal network, sensorimotor network and default mode network. In particular, the Fc strength at the insula of the DAN and the mean FA were linearly related with attention performance and dizziness severity, respectively. The multivariate pattern classification gave over 90% predictive accuracy of individuals with MCI or severe dizziness. Cognitive decline in stroke-free individuals with severe carotid stenosis may arise from nonselective widespread disconnections of long-range, predominantly interhemispheric non-hippocampal pathways. Connectivity measures may serve as both predictors for
Full Text Available BACKGROUND: Cortical changes associated with cognitive decline in Parkinson's disease (PD are not fully explored and require investigations with established diagnostic classification criteria. OBJECTIVE: We used MRI source-based morphometry to evaluate specific differences in grey matter volume patterns across 4 groups of subjects: healthy controls (HC, PD with normal cognition (PD-NC, PD with mild cognitive impairment (MCI-PD and PD with dementia (PDD. METHODS: We examined 151 consecutive subjects: 25 HC, 75 PD-NC, 29 MCI-PD, and 22 PDD at an Italian and Czech movement disorder centre. Operational diagnostic criteria were applied to classify MCI-PD and PDD. All structural MRI images were processed together in the Czech centre. The spatial independent component analysis was used to assess group differences of local grey matter volume. RESULTS: We identified two independent patterns of grey matter volume deviations: a Reductions in the hippocampus and temporal lobes; b Decreases in fronto-parietal regions and increases in the midbrain/cerebellum. Both patterns differentiated PDD from all other groups and correlated with visuospatial deficits and letter verbal fluency, respectively. Only the second pattern additionally differentiated PD-NC from HC. CONCLUSION: Grey matter changes in PDD involve areas associated with Alzheimer-like pathology while fronto-parietal abnormalities are possibly an early marker of PD cognitive decline. These findings are consistent with a non-linear cognitive progression in PD.
Cleutjens, Fiona AHM; Franssen, Frits ME; Spruit, Martijn A; Vanfleteren, Lowie EGW; Gijsen, Candy; Dijkstra, Jeanette B; Ponds, Rudolf WHM; Wouters, Emiel FM; Janssen, Daisy JA
Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls. PMID:28031706
Sheorajpanday, Rishi V. A.; Marien, Peter; Nagels, Guy; Weeren, Arie J. T. M.; Saerens, Jos; van Putten, Michel J. A. M.; De Deyn, Peter P.
Background and Purpose:Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG p
Full Text Available Abstract Background A challenge to individuals with cognitive impairments in wayfinding is how to remain oriented, recall routines, and travel in unfamiliar areas in a way relying on limited cognitive capacity. While people without disabilities often use maps or written directions as navigation tools or for remaining oriented, this cognitively-impaired population is very sensitive to issues of abstraction (e.g. icons on maps or signage and presents the designer with a challenge to tailor navigation information specific to each user and context. Methods This paper describes an approach to providing distributed cognition support of travel guidance for persons with cognitive disabilities. A solution is proposed based on passive near-field RFID tags and scanning PDAs. A prototype is built and tested in field experiments with real subjects. The unique strength of the system is the ability to provide unique-to-the-user prompts that are triggered by context. The key to the approach is to spread the context awareness across the system, with the context being flagged by the RFID tags and the appropriate response being evoked by displaying the appropriate path guidance images indexed by the intersection of specific end-user and context ID embedded in RFID tags. Results We found that passive RFIDs generally served as good context for triggering navigation prompts, although individual differences in effectiveness varied. The results of controlled experiments provided more evidence with regard to applicabilities of the proposed autonomous indoor wayfinding method. Conclusions Our findings suggest that the ability to adapt indoor wayfinding devices for appropriate timing of directions and standing orientation will be particularly important.
Felipe Kenji Sudo
Full Text Available Vascular mild cognitive impairment (VaMCI represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. Methods Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15 were compared to normal controls (NC, n=11 and correlated with Fazekas scale. Results VaMCI performed significantly worse than NC in Trail-Making Test (TMT B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors, difference TMT B-A and CAMCOG total score. Conclusion Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.
Arielle N. Valdez
Full Text Available As individuals live longer with HIV, this “graying of the HIV epidemic” has introduced a new set of challenges including a growing number of age and inflammation-related diseases such as cardiovascular disease, type II diabetes, cancer, and dementia. The biological underpinnings of these complex and co-morbid diseases are not fully understood and become very difficult to disentangle in the context of HIV and aging. In the current review we examine the contributions and interactions of HIV, stress, and cognitive impairment and query the extent to which inflammation is the linchpin in these dynamic interactions. Given the inter-relatedness of stress, inflammatory mechanisms, HIV, and cognitive impairment, future work will either need to address multiple dimensions simultaneously or embrace the philosophy that breaking the aberrant cycle at any one point will subsequently remedy the other related systems and processes. Such a single-point intervention may be effective in early disease states, but after perpetuation of an aberrant cycle, adaptations in an attempt to internally resolve the issue will likely lead to the need for multifaceted interventions. Acknowledging that HIV, inflammation, and stress may interact with one another and collectively impact cognitive ability is an important step in fully understanding an individual's complete clinical picture and moving towards personalized medicine.
Full Text Available Ida Vikan Rise,1 Josep Maria Haro,2–4 Bjørn Gjervan,5,61Department of Psychiatry, Sorlandet Hospital, Arendal, Norway; 2Research Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Spain; 3Faculty of Medicine, Universitat de Barcelona, Barcelona, Spain; 4CIBERSAM (Centro de Investigación Biomédica En Red de Salud Mental, Madrid, Spain; 5Department of Psychiatry, North-Trondelag Hospital Trust, Levanger, Norway; 6Department of Medicine, Institute of Neuromedicine, Norwegian University of Science and Technology, Trondheim, NorwayIntroduction: Data specific to late-life bipolar disorder (BD are limited. Current research is sparse and present guidelines are not adapted to this group of patients.Objectives: We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late-life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment.Methods: Eligible studies were identified in MedLine by the Medical Subject Headings terms “bipolar disorder” and “aged”. We only included original research reports published in English between 2012 and 2015.Results: From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age-matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested.Conclusion: There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that
Full Text Available Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localised white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI.Methods: 25 patients with MCI and 20 age, sex and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI. Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusions: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive
Morais, Talita Cavalcante; Arruda, Bruno Rodrigues; de Sousa Magalhães, Hebert; Trevisan, Maria Teresa Salles; de Araújo Viana, Daniel; Rao, Vietla Satyanarayana; Santos, Flavia Almeida
Our previous study has shown that mangiferin (MGF), a glucosylxanthone from Mangifera indica, exerts gastrointestinal prokinetic action involving a cholinergic mechanism. Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. The present study investigated to know whether MGF having anti-inflammatory and prokinetic actions can ameliorate the intestinal inflammation and impaired gastrointestinal transit seen in the mouse model of POI. Experimental POI was induced in adult male Swiss mice by standardized small intestinal manipulation (IM). Twenty-four hours later, gastrointestinal transit was assessed by charcoal transport. MGF was administered orally 1 h before the measurement of GIT. To evaluate the inflammatory response, plasma levels of proinflammatory cytokines TNF-α, IL-1β, IL-6, and chemokine MCP-1, and the myeloperoxidase activity, nitrate/nitrite level, and histological changes of ileum were determined in mice treated or not with MGF. Experimental POI in mice was characterized by decreased gastrointestinal transit and marked intestinal and systemic inflammatory response. MGF treatment led to recovery of the delayed intestinal transit induced by IM. MGF in ileum significantly inhibited the myeloperoxidase activity, a marker of neutrophil infiltration, and nitrate/nitrite level and reduced the plasma levels of TNF-α, IL-1β, IL-6, and MCP-1 as well. MGF treatment ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in the mouse model of POI.
Full Text Available Abstract Background The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI. However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. Methods A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD, and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test between MCI and healthy elderly and between MCI and mild AD groups. Results Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p Conclusions Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia.
Conclusion: Lacunes are important predictors of cognitive impairment in SVD. We highlight the importance of spatial distribution, particularly of anteromedial thalamic lacunes which are associated with impaired information processing speed and may mediate cognitive impairment via disruption of connectivity to the prefrontal cortex.
Bathelt, J. M. C.
Previous studies identified cognitive difficulties in individuals with congenital visual impairment that significantly impacted on wellbeing and educational attainment. However, factors leading to adverse outcome remained unclear. The current study aimed to identify associations and mechanisms of specific cognitive deficits associated with visual impairment from a neurodevelopmental perspective. Based on recent theoretical advances (Johnson, 2011), it was assumed that visual impairment leads ...
Full Text Available To determine the influence of social support on cognitive impairment among elderly Malaysians. Methods This cross sectional study was conducted using a representative sample for Penang, Malaysia. The Elderly Cognitive Assessment Questionnaire (ECAQ was used to screen for cognitive impairment and Oslo-3 Social Support Scale (OSS-3 was used to measure social support.
Full Text Available Abstract Background Paramedics are often a first point of contact for people experiencing pain in the community. Wherever possible the patient's self report of pain should be sought to guide the assessment and management of this complaint. Communication difficulty or disability such as cognitive impairment associated with dementia may limit the patient's ability to report their pain experience, and this has the potential to affect the quality of care. The primary objective of this study was to systematically locate evidence relating to the use of pain assessment tools that have been validated for use with cognitively impaired adults and to identify those that have been recommended for use by paramedics. Methods A systematic search of health databases for evidence relating to the use of pain assessment tools that have been validated for use with cognitively impaired adults was undertaken using specific search criteria. An extended search included position statements and clinical practice guidelines developed by health agencies to identify evidence-based recommendations regarding pain assessment in older adults. Results Two systematic reviews met study inclusion criteria. Weaknesses in tools evaluated by these studies limited their application in assessing pain in the population of interest. Only one tool was designed to assess pain in acute care settings. No tools were located that are designed for paramedic use. Conclusion The reviews of pain assessment tools found that the majority were developed to assess chronic pain in aged care, hospital or hospice settings. An analysis of the characteristics of these pain assessment tools identified attributes that may limit their use in paramedic practice. One tool - the Abbey Pain Scale - may have application in paramedic assessment of pain, but clinical evaluation is required to validate this tool in the paramedic practice setting. Further research is recommended to evaluate the Abbey Pain Scale and to
Hall, F Scott; Der-Avakian, Andre; Gould, Thomas J; Markou, Athina; Shoaib, Mohammed; Young, Jared W
Smokers have substantial individual differences in quit success in response to current treatments for nicotine dependence. This observation may suggest that different underlying motivations for continued tobacco use across individuals and nicotine cessation may require different treatments in different individuals. Although most animal models of nicotine dependence emphasize the positive reinforcing effects of nicotine as the major motivational force behind nicotine use, smokers generally report that other consequences of nicotine use, including the ability of nicotine to alleviate negative affective states or cognitive impairments, as reasons for continued smoking. These states could result from nicotine withdrawal, but also may be associated with premorbid differences in affective and/or cognitive function. Effects of nicotine on cognition and affect may alleviate these impairments regardless of their premorbid or postmorbid origin (e.g., before or after the development of nicotine dependence). The ability of nicotine to alleviate these symptoms would thus negatively reinforce behavior, and thus maintain subsequent nicotine use, contributing to the initiation of smoking, the progression to dependence and relapse during quit attempts. The human and animal studies reviewed here support the idea that self-medication for pre-morbid and withdrawal-induced impairments may be more important factors in nicotine addiction and relapse than has been previously appreciated in preclinical research into nicotine dependence. Given the diverse beneficial effects of nicotine under these conditions, individuals might smoke for quite different reasons. This review suggests that inter-individual differences in the diverse effects of nicotine associated with self-medication and negative reinforcement are an important consideration in studies attempting to understand the causes of nicotine addiction, as well as in the development of effective, individualized nicotine cessation
Kehagia, Angie A.; Barker, Roger A.; Robbins, Trevor W.
Research into the heterogeneous nature of cognitive impairment documented in patients with Parkinson's disease (PD) has focused on disentangling deficits that vary between individuals, evolve and respond differentially to pharmacological treatments, and relate differentially to PD dementia (PDD). We summarise studies conducted in our laboratory over the last 2 decades, outlining the incremental development of our hypotheses, the starting point for which is our early work on executive deficits mirroring fronto-striatal dysfunction. We present subsequent findings linking these deficits to a model of dopaminergic function that conforms to an inverted curvilinear function. We review studies that investigated the range of dopamine-independent attentional and visuospatial memory deficits seen in PD, demonstrating that abnormalities in these domains more accurately predict PDD. We conclude with an exposition of the dual syndrome hypothesis, which distinguishes between dopaminergically mediated fronto-striatal executive impairments and a dementia syndrome with distinctive prodromal visuospatial deficits in which cholinergic treatments offer some clinical benefits. PMID:23038420
Schepker, Caroline A; Leveille, Suzanne G; Pedersen, Mette Merete;
OBJECTIVES: To examine the effect of pain and mild cognitive impairment (MCI)-together and separately-on performance-based and self-reported mobility outcomes in older adults in primary care with mild to moderate self-reported mobility limitations. DESIGN: Cross-sectional analysis. SETTING...... mobility, and the presence of both comorbidities was associated with the poorest status. Primary care practitioners who encounter older adults in need of mobility rehabilitation should consider screening them for pain and MCI to better inform subsequent therapeutic interventions.......: Academic community outpatient clinic. PARTICIPANTS: Individuals aged 65 and older in primary care enrolled in the Boston Rehabilitative Impairment Study in the Elderly who were at risk of mobility decline (N = 430). MEASUREMENTS: Participants with an average score greater than three on the Brief Pain...
Schmidt, Norman B; Eggleston, A Meade; Woolaway-Bickel, Kelly; Fitzpatrick, Kathleen Kara; Vasey, Michael W; Richey, J Anthony
Fear of arousal symptoms, often referred to as anxiety sensitivity (AS) appears to be associated with risk for anxiety pathology and other Axis I conditions. Findings from a longitudinal prevention program targeting AS are reported. Participants (n=404) scoring high on the Anxiety Sensitivity Index (ASI) were randomly assigned to receive a brief intervention designed to reduce AS (Anxiety Sensitivity Amelioration Training (ASAT)) or a control condition. Participants were followed for up to 24 months. Findings indicate that ASAT produced greater reductions in ASI levels compared with the control condition. Moreover, reductions were specific to anxiety sensitivity relative to related cognitive risk factors for anxiety. ASAT also produced decreased subjective fear responding to a 20% CO(2) challenge delivered postintervention. Data from the follow-up period show a lower incidence of Axis I diagnoses in the treated condition though the overall group difference was not statistically different at all follow-up intervals. Overall, findings are promising for the preventative efficacy of a brief, computer-based intervention designed to decrease anxiety sensitivity.
Full Text Available The present study was designed to probe the effects of Huperzine A (HupA on diabetes-associated cognitive decline (DACD using a streptozotocin (STZ-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT, Acetylcholinesterase (AChE, malondialdehyde (MDA, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, catalase (CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.
Peraita, Herminia; Chacón, José; Díaz-Mardomingo, Carmen; Martínez-Arias, Rosario
We applied latent class analysis (LCA) to a set of neuropsychological data with the aim of corroborating the three cognitive profiles of mild cognitive impairment (MCI) described in the literature, namely: healthy, amnestic, non-amnestic, and multidomain. The ultimate purpose of the LCA was to try to find the underlying classification of MCI and related pathologies by means of the participants' response patterns, rather than on more classical psychometric criteria, such as the standard deviation of the mean. We computed 547 neuropsychological assessments derived from 223 participants who were assessed annually for three consecutive years. The battery included tests of memory, language, executive function, and praxis. The results obtained by means of LCA, with a four-group solution and using the 40th percentile as the criterion, confirm prior classifications obtained with more questionable psychometric criteria, while providing longitudinal data on the course of MCI and the stability of group assignment over time.
Full Text Available BACKGROUND: The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients' depression levels were negatively correlated with performance on empathy tasks. CONCLUSIONS/SIGNIFICANCE: Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.
Popp, Julius; Schaper, Karsten; Kölsch, Heike; Cvetanovska, Gabriela; Rommel, Fatima; Klingmüller, Dietrich; Dodel, Richard; Wüllner, Ullrich; Jessen, Frank
Hypercortisolaemia occurs in Alzheimer's disease (AD) and may be involved in the AD related neurodegenerative process. In order to determine whether brain structures are exposed to high cortisol concentrations early in AD, we measured cerebrospinal fluid (CSF) cortisol in 66 subjects with AD, 33 subjects with mild cognitive impairment (MCI) and 34 control subjects. CSF cortisol concentrations were higher in AD subjects compared to controls (pcortisol in MCI subjects compared with controls suggesting that the increase of CSF cortisol is not an early event in the course of AD.
Full Text Available Approximately five million people suffer with Alzheimer disease (AD and more than twenty-four million people are diagnosed with AD, pre-senile dementia, and other disorders of cognitive loss worldwide. Furthermore, the annual cost per patient with AD can approach $200,000 with an annual population aggregate cost of $100 billion. Yet, complete therapeutic prevention or reversal of neurovascular injury during AD and cognitive loss is not achievable despite the current understanding of the cellular pathways that modulate nervous system injury during these disorders. As a result, identification of novel therapeutic targets for the treatment of neurovascular injury would be extremely beneficial to reduce or eliminate disability from diseases that lead to cognitive loss or impairment. Here we describe the capacity of intrinsic cellular mechanisms for the novel pathways of erythropoietin and forkhead transcription factors that may offer not only new strategies for disorders such as AD and cognitive loss, but also function as biomarkers for disease onset and progression.
Moro, V; Condoleo, M T; Valbusa, V; Broggio, E; Moretto, G; Gambina, G
Executive functions play an important role in the maintenance of autonomy in day-to-day activities. Nevertheless, there is little research into specific cognitive training for Mild Cognitive Impairment (MCI). We present the results of a program which aims to teach specific strategies and metacognitive abilities in order for patients to be able to carry out attentional and executive tasks. Two groups (A and B) were compared in a cross-over design. After the first evaluation, Group A (but not B) participated in a six month cognitive stimulation program. After a second assessment, only Group B received treatment and then a final evaluation was carried out on both groups. The results show that: i) both groups improved their performance as an effect of training; ii) improvements generalized to memory and general cognitive tasks; iii) in the interval without training, Group B's performance worsened and iv) Group A partially maintained their results over time.
Koivunen, Jaana; Karrasch, Mira; Scheinin, Noora M
Background/Aims: The relationship between baseline (11)C-Pittsburgh compound B ((11)C-PIB) uptake and cognitive decline during a 2-year follow-up was studied in 9 patients with mild cognitive impairment (MCI) who converted to Alzheimer's disease (AD) and 7 who remained with MCI. Methods: (11)C-PIB...... PET scan was conducted at baseline and cognitive assessment both at baseline and at follow-up. To obtain quantitative regional values of (11)C-PIB uptake, automated region of interest analysis was done using spatially normalized parametric ratio (region-to-cerebellar cortex) images. Results......: At baseline, there were statistically significant differences in (11)C-PIB uptake, but not in cognitive test performances between the converters and nonconverters. Memory and executive function declined only in the converters during follow-up. In the converters, lower baseline frontal (11)C-PIB uptake...
Atkinson, Joanna; Denmark, Tanya; Marshall, Jane; Mummery, Cath; Woll, Bencie
To provide accurate diagnostic screening of deaf people who use signed communication, cognitive tests must be devised in signed languages with normative deaf samples. This article describes the development of the first screening test for the detection of cognitive impairment and dementia in deaf signers. The British Sign Language Cognitive Screening Test uses standardized video administration to screen cognition using signed, rather than spoken or written, instructions and a large norm-referenced sample of 226 deaf older people. Percentiles are provided for clinical comparison. The tests showed good reliability, content validity, and correlation with age, intellectual ability, and education. Clinical discrimination was shown between the normative sample and 14 deaf patients with dementia. This innovative testing approach transforms the ability to detect dementia in deaf people, avoids the difficulties of using an interpreter, and enables culturally and linguistically sensitive assessment of deaf signers, with international potential for adaptation into other signed languages.
Chen, Guan-Qun; Zhang, Yi-He; Li, Xuan-Yu; Hao, Xu-Yang; Yu, Yang; Zhang, Meng; Sheng, Can; Li, Yu-Xia; Sun, Yu; Li, Hong-Yan; Song, Yang; Li, Kun-Cheng; Yan, Tian-Yi; Tang, Xiao-Ying; Han, Ying
Network analysis has been widely used in studying Alzheimer's disease (AD). However, how the white matter network changes in cognitive impaired patients with subjective cognitive decline (SCD) (a symptom emerging during early stage of AD) and amnestic mild cognitive impairment (aMCI) (a pre-dementia stage of AD) is still unclear. Here, structural networks were constructed respectively based on FA and FN for 36 normal controls, 21 SCD patients, and 33 aMCI patients by diffusion tensor imaging and graph theory. Significantly lower efficiency was found in aMCI patients than normal controls (NC). Though not significant, the values in those with SCD were intermediate between aMCI and NC. In addition, our results showed significantly altered betweenness centrality located in right precuneus, calcarine, putamen, and left anterior cingulate in aMCI patients. Furthermore, association was found between network metrics and cognitive impairment. Our study suggests that the structural network properties might be preserved in SCD stage and disrupted in aMCI stage, which may provide novel insights into pathological mechanisms of AD. PMID:27418146
Rajesh, Venugopalan; Ilanthalir, Sakthivel
Several epidemiological studies have shown that consumption of large quantities of vegetables especially cruciferous vegetables (Broccoli and Brussels sprouts) can protect against chronic diseases. Sulforaphane, an isothiocynate found in cruciferous vegetables has been demonstrated to have neuroprotective effects in several experimental paradigms. This study was undertaken to examine the effect of sulforaphane on cognitive impairment in zebra fish model using a novel method of fear conditioning. Initially, the normal behaviour of zebra fishes was studied in light-dark tank for 10 min daily for 10 days. Fishes were then divided into seven groups of twelve in each. Group I served as normal, group II served as fear conditioned control, group III and group IV were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated respectively. Group V served as scopolamine (400 µM/L) induced memory impairment fishes. Group VI and VII were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated scopolamine induced memory impairment groups respectively. In normal behavioural analysis, fishes preferred to stay in dark compartment. The average number of entries into the dark and time spent in dark were significantly more. Fishes in group II to VII were individually subjected to fear conditioning passive avoidance task and evaluated for learned task memory. It was observed that the average number of entries into dark and time spent in dark were significantly decreased. After exposure to respective treatment fishes in group III to VII were subjected to cognitive evaluation. There was no significant difference in cognition of group III and IV fishes exposed to sulforaphane and piracetam alone respectively. Fishes exposed to scopolamine showed a significant cognitive impairment. Sulforaphane exposure prior to scopolamine significantly retained the memory of learned task. These findings suggest that sulforaphane might be a promising therapeutic agent for cognitive enhancement in
Leigh A Johnson
Full Text Available BACKGROUND: Alzheimer's disease (AD is a devastating public health problem that affects over 5.4 million Americans. Depression increases the risk of Mild Cognitive Impairment (MCI and AD. By understanding the influence of depression on cognition, the potential exists to identify subgroups of depressed elders at greater risk for cognitive decline and AD. The current study sought to: 1 clinically identify a sub group of geriatric patients who suffer from depression related cognitive impairment; 2 cross validate this depressive endophenotype of MCI/AD in an independent cohort. METHODS AND FINDINGS: Data was analyzed from 519 participants of Project FRONTIER. Depression was assessed with the GDS30 and cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to create the Depressive endophenotype of MCI and AD (DepE. DepE was significantly negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37, p<0.001, visuospatial skills (B=-1.11, SE=0.26, p<0.001, Language (B=-1.03, SE=0.21, p<0.001, Attention (B=-2.56, SE=0.49, p<0.001, and Delayed Memory (B=-1.54, SE = 037, p<0.001, and higher DepE scores were related to poorer executive functioning (EXIT25; B=0.65, SE=0.19, p=0.001. DepE scores significantly increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69. Data from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium were analyzed for cross-validation of findings in an independent cohort. The DepE was significantly related to poorer scores on all measures, and a significantly predicted of cognitive change over 12- and 24-months. CONCLUSION: The current findings suggest that a depressive endophenotype of MCI and AD exists and can be clinically identified using the GDS-30. Higher scores increased risk for MCI and was cross-validated by predicting AD in the TARCC. A key purpose for the search for distinct subgroups of individuals at risk for AD and MCI is to identify
Full Text Available Nicola Gates,1–3 Michael Valenzuela,3 Perminder S Sachdev,1,2,4 Maria A Fiatarone Singh5,61School of Psychiatry, 2Centre for Healthy Brain Ageing (CheBA, University of New South Wales, Sydney, NSW, Australia; 3Regenerative Neuroscience Group, Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia; 4Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia; 5Exercise Health and Performance Faculty Research Group, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia; 6Hebrew SeniorLife, Boston, MA, and Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USAObjectives: Cognitive impairments associated with aging and dementia are major sources of burden, deterioration in life quality, and reduced psychological well-being (PWB. Preventative measures to both reduce incident disease and improve PWB in those afflicted are increasingly targeting individuals with mild cognitive impairment (MCI at early disease stage. However, there is very limited information regarding the relationships between early cognitive changes and memory concern, and life quality and PWB in adults with MCI; furthermore, PWB outcomes are too commonly overlooked in intervention trials. The purpose of this study was therefore to empirically test a theoretical model of PWB in MCI in order to inform clinical intervention.Methods: Baseline data from a convenience sample of 100 community-dwelling adults diagnosed with MCI enrolled in the Study of Mental Activity and Regular Training (SMART trial were collected. A series of regression analyses were performed to develop a reduced model, then hierarchical regression with the Baron Kenny test of mediation derived the final three-tiered model of PWB.Results: Significant predictors of PWB were subjective memory concern, cognitive function, evaluations of quality of life, and negative affect, with a final model explaining 61% of the variance
Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla
Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.
Kim, Eun-Hee; Ko, Tae-Sung
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.
Kubicki, Alexandre; Fautrelle, Lilian; Bourrelier, Julien; Rouaud, Olivier; Mourey, France
Objectives: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity in muscle synergies involved in an arm-pointing movement in functionally unimpaired MCI patients. We hypothesized that early motor indicators exist in this population at a preclinical level. Methods: Electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Older Adults (OA), and MCI patients. The OA and MCI groups presented the same functional status. Each subject performed 20 arm-pointing movements from a standing position. Results: The main differences were (1) an earlier activation of the left Obliquus internus in MCI compared with OA group, (2) an earlier activation for the MCI compared with both OA and YA. The temporal differences in muscle synergies between MCI and OA groups were linked with executive functions of MCI patients, assessed by the trail making test. Moreover, the results show a delayed activation of the right Biceps Femoris and the right Erector Spinae at l3 in MCI and OA compared with YA. Interpretation: The motor program changes highlighted in our patient MCI group suggest that discrete modifications of the motor command seem to exist even in the absence of functional impairment. Instead of showing an indication of delayed muscle activation in the MCI patients, our results highlight some early activation of several trunk muscles. PMID:27570509
Mann, Claire L; Footer, Owen; Chung, Yu Sun; Driscoll, Lori L; Barch, Deanna M
The ability to upregulate cognitive control in motivationally salient situations was examined in individuals with schizophrenia (patients) and healthy controls. Fifty-four patients and 39 healthy controls were recruited. A computerized monetary response conflict task required participants to identity a picture, over which was printed a matching (congruent), neutral, or incongruent word. This baseline condition was followed by an incentive condition, in which participants were given the opportunity to win money on reward-cued trials. These reward-cued trials were interleaved with nonreward cued trials. Reaction times (RT) were examined for both incentive context effects (difference in RT between baseline and nonreward cue trials in the incentive condition) and incentive cue effects (difference in RT between nonreward and reward cue trials in the incentive condition). Compared with baseline, controls showed a speeding of responses during both the nonreward (incentive context effect) and reward cued (incentive cue effect) trials during the incentive condition, but with a larger incentive context than incentive cue effect, suggesting a reliance on proactive control strategies. Although patients also showed a speeding of responses to both nonreward and reward cued trials, they showed a significantly smaller incentive context effect than controls, suggesting a reduction in the use of proactive control and a greater reliance on the use of "just-in-time," reactive control strategies. These results are discussed in light of the relationship between motivation and cognitive impairments in schizophrenia, and the potential role of impairments in prefrontally mediated active maintenance mechanisms.
Sakakibara, Ryuji; Ogata, Takeshi; Haruta, Masayuki; Kishi, Masahiko; Tsuyusaki, Yohei; Tateno, Akihiko; Tateno, Fuyuki; Mouri, Takayuki
Objectives: We reported cases of amnestic mild cognitive impairment (MCI) without the core clinical features of dementia with Lewy bodies (DLB) (dementia and spontaneous parkinsonism) with low uptake in 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. Methods: During a 3-year period at a university clinic, we had 254 patients with memory complaints; 106 men, 148 women; mean age 72.5 years (48-95 years). In all patients we performed neurologic examination; memory tests including the MMSE, ADAScog, FAB and additional WMS-R; and imaging tests including brain MRI, SPECT and MIBG scintigraphy. Results: The criteria of amnestic MCI were fulfilled in 44 patients; and 13 of them (30%) showed low MIBG uptake. They had the following: uniformly elderly, with an equal sex ratio, have relatively slow progression, preserved general cognitive function (MMSE 24.8/30). In addition to memory impairment, they commonly showed low frontal function by FAB (12.5/18) and some had mild visual hallucination (5). Other than memory disorder, they had autonomic disorder (nocturia in 7, constipation in 2, postural hypotension in one), REM sleep behavioral disorder (in 3) and occipital hypoperfusion by SPECT (in 5). Conclusion: This cohort of multidomain amnestic MCI cases may present with early stage DLB because of the presence of low MIBG uptake. Clinically, they commonly have low FAB, and may have visual hallucination, autonomic and sleep disorders. PMID:23383388
Full Text Available Mild cognitive impairment (MCI is considered a transitional stage between healthy aging and dementia, specifically Alzheimer’s disease (AD. The most common cognitive impairment of MCI includes episodic memory loss and difficulties in working memory (WM. Interference can deplete WM, and an optimal WM performance requires an effective control of attentional resources between the memoranda and the incoming stimuli. Difficulties in handling interference lead to forgetting. However, the interplay between interference and WM in MCI is not well understood and needs further investigation. The current study investigated the effect of interference during a WM task in 20 MCIs and 20 healthy elder volunteers. Participants performed a delayed match-to-sample paradigm which consisted in two interference conditions, distraction and interruption, and one control condition without any interference. Results evidenced a disproportionate impact of interference on the WM performance of MCIs, mainly in the presence of interruption. These findings demonstrate that interference, and more precisely interruption, is an important proxy for memory-related deficits in MCI. Thus the current findings reveal novel evidence regarding the causes of WM forgetting in MCI patients, associated with difficulties in the mechanisms of attentional control.
Aurtenetxe, Sara; García-Pacios, Javier; del Río, David; López, María E.; Pineda-Pardo, José A.; Marcos, Alberto; Delgado Losada, Maria L.; López-Frutos, José M.; Maestú, Fernando
Mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia, specifically Alzheimer's disease (AD). The most common cognitive impairment of MCI includes episodic memory loss and difficulties in working memory (WM). Interference can deplete WM, and an optimal WM performance requires an effective control of attentional resources between the memoranda and the incoming stimuli. Difficulties in handling interference lead to forgetting. However, the interplay between interference and WM in MCI is not well-understood and needs further investigation. The current study investigated the effect of interference during a WM task in 20 MCIs and 20 healthy elder volunteers. Participants performed a delayed match-to-sample paradigm which consisted in two interference conditions, distraction and interruption, and one control condition without any interference. Results evidenced a disproportionate impact of interference on the WM performance of MCIs, mainly in the presence of interruption. These findings demonstrate that interference, and more precisely interruption, is an important proxy for memory-related deficits in MCI. Thus, the current findings reveal novel evidence regarding the causes of WM forgetting in MCI patients, associated with difficulties in the mechanisms of attentional control. PMID:27790082
Armstrong, Carol L., E-mail: firstname.lastname@example.org [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States); Shera, David M. [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Department of Pediatrics, Division of Biostatistics and Epidemiology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States); Lustig, Robert A. [Department of Radiation Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States); Phillips, Peter C. [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Department of Pediatrics, Division of Neurology and Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States)
Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.
Nitin Natthuji Puram
Conclusions: Telmisartan is as effective as losartan in controlling blood pressure and improving cognitive function in hypertensive patients with cognitive impairment. [Int J Basic Clin Pharmacol 2016; 5(3.000: 702-706
Olsen, Line; Rasmussen, Henrik B; Hansen, Thomas;
The estrogen receptor alpha (ESR1) gene has been implicated in the process of cognitive impairment in elderly women. In a paired case-control study, we tested whether two ESR1 gene polymorphisms (the XbaI and PvuII sites) are risk factors for cognitive impairment as measured by the six-item Orien......The estrogen receptor alpha (ESR1) gene has been implicated in the process of cognitive impairment in elderly women. In a paired case-control study, we tested whether two ESR1 gene polymorphisms (the XbaI and PvuII sites) are risk factors for cognitive impairment as measured by the six...
O'Leary, M R; Calsyn, D A; Fauria, T
The Group Embedded Figures Test (GEFT) purports to be a measure of field articulation. The extent to which the GEFT measures apsects of personality and cognitive impairment was explored. Eighty-one male alcoholics, mean age of 42.9, receiving treatment for alcoholism at the Seattle VA Medical Center were administered the GEFT, Shipley Hartford Institute of Living Scale, the Trail Making Test (TMT), and the Clinical Analysis Questionnaire (CAQ). Multiple regression analysis indicates that Part B of the TMT and the residual abstraction score from the Shipley share 32% of the common variance with GEFT. The CAQ second-order factors of depression and independence also contributed significantly to the regression equation accounting for an additional 10% of the common variance. The results suggest the GEFT may be more a measure of cognitive impairment than personality. Alternative explanations are explored.
Migo, E M; Westerberg, C E
There is some debate over the relative impairment of recollection and familiarity in mild cognitive impairment (MCI). A recent publication by Algarabel et al. (2012, Recognition memory deficits in mild cognitive impairment, Aging, Neuropsychology, and Cognition, 19, 608-619) claims to undermine previous studies reporting preserved familiarity in patients with MCI. Here, we respond to their main criticisms, concluding that they are not sufficiently supported by the data presented. The role of recollection and familiarity in MCI remains unresolved and further work will be required to disentangle the mixed literature.
Natalia Vyacheslavovna Pizova
Full Text Available The paper gives an update on the pathogenesis, clinical presentation, and pathomorphology of cognitive impairments (CIs in different autoimmune, endocrine, and infectious diseases, such as systemic lupus erythematosus, Sjögren's syndrome, BehНet's disease, primary angiitis of the central nervous system, polyarteritis nodosa, cryoglobulinemic vasculitis, hypothyroidism, herpetic lesion, and neurosyphilis. These patients are observed to have ischemic-hypoxic brain damage, the causes of which are free radical-induced cell injury, oxidative stress, excitation toxicity, cell necrosis and/or apoptosis, inflammation and immune disease, molecular sequestration, and cell death. There is enhanced imbalance in the pro-oxidant and antioxidant systems as cerebrovascular insufficiency progresses; as this takes place, the nerve cells are most susceptible to the induction of free radical reactions. In these cases, antioxidants that block the effects of free radicals and may potentially improve brain perfusion, by assisting the coupling of neurons and vessels, are first-choice drugs. To improve the cognitive status and to prevent the progression of CIs, it is important to build a cognitive reserve in a patient; this is largely favored by the preservation of a proactive approach to life and social bonds, as well as intellectual work.
Natalia Vyacheslavovna Pizova
Full Text Available Stroke is a leading cause of disability not only due to its impact on motor or sensory functions, but also to post-stroke cognitive impairments (CI. Within the first year after stroke, the rate of CI may be as high as 80-90% and 7-23% of patients develop dementia. The most important risk factors for CI are strokes, their extent, site, and number. Old age, low education level, severe previous pathological changes in the brain parenchyma, diabetes mellitus, atrial fibrillations, and recurrent strokes in particular, are associated with an increased risk of CI. Examining cognitive functions, monitoring the evolution of cognitive deficit, and post-stroke rehabilitation are indicated in patients who have had stroke. The main treatments in patients with CI are secondary stroke prevention, including lifestyle modification and symptomatic therapy. Sermion is one of the promising agents for the prevention and treatment of CI in these patients.
Full Text Available This study aimed to examine the experience and knowledge of mild cognitive impairment (MCI among Chinese family caregivers of individuals with MCI. The sample was recruited from memory clinics in Zhongnan Hospital in Wuhan, China. In-depth semi-structured interviews were used. Thirteen family members of individuals diagnosed with MCI participated in the study. Data analysis revealed three themes: 1 initial recognition of cognitive decline; 2 experience of the diagnosis of MCI; 3 perception of cognitive decline as a normal part of aging. While family members recognized the serious consequences of memory loss (e.g. getting lost, they would typically not take their family members to see a doctor until something specific triggered their access to the medical care system. The Chinese traditional perception of dementia as part of normal aging may serve to lessen the stigma of individuals with MCI, while the term "laonian chidai" which literally translates to "stupid, demented elderly" may exacerbate the stigma associated with individuals with MCI. It is suggested that family members' worries may be relieved by improving their access to accurate knowledge of the disease, community-based and institutional care services, and culturally appropriately words are needed for MCI.
Dubey, Shagun; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen
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
Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki
We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus.
Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Khoo, Tien K; Breen, David P; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J
We evaluated the association between mild cognitive impairment (MCI) subtypes and quality of life (QoL) in 219 newly diagnosed Parkinson's disease (PD) patients without dementia. Participants completed neuropsychological tests of attention, executive function, visuospatial function, memory, and language, and reported QoL using the Parkinson's Disease Questionnaire. Impairments were most common in executive function, memory and attention. MCI subtypes were classified according to Movement Disorder Society Task Force criteria. More severe cognitive impairment was associated with poorer quality of life (p = 0.01), but subtype of impairment was not (p > 0.10), suggesting that the nature of cognitive impairment is less significant than its severity.
Full Text Available Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB from Alzheimer's disease (AD at the mild cognitive impairment (MCI stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25 and AD (MCI-AD: n = 28 at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9 detected in 72% of patients, followed by REM sleep behavior disorder (60% and fluctuations (60%. Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.
Cagnin, Annachiara; Bussè, Cinzia; Gardini, Simona; Jelcic, Nela; Guzzo, Caterina; Gnoato, Francesca; Mitolo, Micaela; Ermani, Mario; Caffarra, Paolo
Objective The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB. PMID:26674638
Full Text Available Objective: The aim of our study is to examine cognitive performance after mild stroke via Mini Mental State Examination (MMSE and Montreal cognitive assessment scale (MoCA and to compare the results.Material and methods: We examined 54 patients with mild stroke (aged 52 to 72 (mean 63.17, SD 5.96; 34 males and 20 females and 54 controls, adjusted by age, sex and education level. All subjects were tested via MMSE (Bulgarian version and MoCa (Bulgarian version. Data was collected in the single step model at the 90th day after stroke incident for patients and at the day of obtaining informed consent for controls. Results: Patients have poorer performance on both MMSE and MoCa than controls. MoCa has comparatively good discriminative validity and sensitivity.Conclusions: Although MMSE is one of the classical screening tools for cognitive impairment widely used in Bulgaria, other screening tools should not be ignored. On the basis of our results, MoCa is also a good screening instrument, especially for poststroke cognitive impairment.
Lucignani, Giovanni [University of Milan and Unit of Molecular Imaging, Division of Radiation Therapy, European Institute of Oncology, Institute of Radiological Sciences, Milan (Italy)
Imaging techniques, including emission tomography and magnetic resonance imaging, are progressively being exploited for the classification and prognostic evaluation (indispensable for possible treatments) of mild cognitive impairment (MCI). The main traits of MCI and unsolved issues in its assessment are discussed in two review articles by Feldman and Jacova from the Division of Neurology, Dept. of Medicine, Clinic for Alzheimer Disease and Related Disorders, University of British Columbia, in Vancouver, Canada  and Chong and Sahadevan from the Department of Geriatric Medicine, Tan Tock Seng Hospital, Jalan Tan Tock Seng, Singapore . Because MCI has different presentations in terms of the type and degree of cognitive deficits observed, several clinical subtypes of MCI besides the amnestic form have now been recognised and characterised on the basis of deficits in different cognitive domains, either in isolation or in combination with amnesia. The different subtypes of MCI suggest that MCI has a heterogeneous nature, with several possible causes that lead to the same symptoms. This is a field in evolution, and a uniform diagnostic classification of MCI has not yet been accomplished. Lopez et al. from the Departments of Neurology and Psychiatry, University of Pittsburgh, School of Medicine,Pittsburgh, Pennsylvania, USA  point out that the classification of MCI subtypes is useful to improve prediction of the subsequent risk of dementia and the type of dementia, and that the manner in which MCI subjects are classified into subgroups has implications for the cognitive profile of the group and thus for our inferences about the aetiology and possible clinical course of the disorder.
Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu
Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.
Full Text Available Abstract Background Research evidence from observational studies suggests that cognitive activity reduces the risk of cognitive impairment in later life as well as the rate of cognitive decline of people with dementia. The Promoting Healthy Ageing with Cognitive Exercise (PACE study has been designed to determine whether a cognitive activity intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment (MCI. Methods/Design The study will recruit 160 community-dwelling men and women aged 65 years of age or over with mild cognitive impairment (MCI. Participants will be randomly allocated to two treatment groups: non-specific education and cognitive activity. The intervention will consist of ten 90-minute sessions delivered twice per week over a period of five weeks. The primary outcome measure of the study is the change from baseline in the total score on the Cambridge Cognitive Score (CAMCOG. Secondary outcomes of interest include changes in memory, attention, executive functions, mood and quality of life. Primary endpoints will be collected 12, 52 and 104 weeks after the baseline assessment. Discussion The proposed project will produce the best available evidence on the merits of increased cognitive activity as a strategy to prevent cognitive decline among older adults with MCI. We anticipate that the results of this study will have implications for the development of evidence-based preventive strategies to reduce the rate of cognitive decline amongst older people at risk of dementia. Trial registration ACTRN12608000556347
Schizophrenia is associated with significant cognitive impairment. Bipolar disorder (BD) also presents with cognitive deficits that are similar to, albeit less severe, than those reported in schizophrenia. There has been controversy over whether selective deficits in social cognition or developmental trajectory of cognitive deficits can distinguish schizophrenia from BD. Also, available studies have not generally considered the potential effect of cognitive heterogeneity within the two disorders on between-group differences. The current review examines the evidence on the specificity of social cognitive deficits and early neurocognitive impairment to schizophrenia and explores the overall outcome of studies investigating within and cross-diagnosis cognitive heterogeneity in schizophrenia and BD. Current evidence does not support the specificity of social cognitive impairment to schizophrenia. Available studies also suggest that cognitive impairment in premorbid and early stages is evident not only in schizophrenia but also in many BD patients. Both schizophrenia and BD have a number of cognitive subgroups, including severe impairment, good functioning, and one or more selective or modest impairment clusters. While both disorders are represented in each cognitive subgroup, there are significant cross-diagnostic differences regarding prevalences of individuals belonging to the severe impairment and good functioning subgroups. Individuals with schizophrenia are much more likely to exhibit severe cognitive impairment than individuals with BD and good cognitive functioning is more often observed in BD patients than schizophrenia patients. Further identification of the neurobiological and genetic characteristics of the cognitive subgroups in major psychoses can improve the validity of diagnostic systems and can advance the development of personalized management approaches, including cognitive remediation.
Sherina, M S; Rampal, L; Mustaqim, A
Cognitive impairment is common in late life and may be due to the normal process of ageing or associated with physical or mental disorders. The aim of this study was to determine the prevalence of cognitive impairment among the elderly in a rural community setting. A cross sectional study design using stratified proportionate cluster sampling method was used in this study. A questionnaire similar to the Elderly Cognitive Assessment Questionnaire (ECAQ) was used as a screening instrument for cognitive impairment. The prevalence of cognitive impairment was 22.4% (50/223) among the elderly respondents. Cognitive impairment among the elderly was significantly associated with age, gender, ethnicity, marital status and level of education.
Full Text Available We compared indices of the revised version of the Wechsler Memory Scale (WMS-R and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R in 30 elderly schizophrenia (ES patients and 25 Alzheimer’s disease (AD patients in the amnestic mild cognitive impairment (aMCI stage (AD-aMCI. In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone.
Full Text Available Objective: to compare a multimodal drug approach to treating poststroke cognitive impairments (CI.Patients and methods. Eighty patients with postroke CI in the early recovery period were examined. They were allocated to 4 groups:1 secondary stroke prevention only (a comparison nontreatment group; 2 actovegin infusions; 3 cerebrolysin infusions; 4 drug therapy in combination with non-drug cognitive training using the standard procedure. Follow-ups and neuropsychological assessments were made at the inclusion in the study and 3 and 6 months after stroke. The state of cognitive functions 6 months after stroke was considered to be an endpoint of the study.Results and discussion. At the inclusion in the study, the mini-mental state examination and the frontal lobe dysfunction scale showed no statistical differences in cognitive functions in different patient groups. At a 3-month follow-up, the cognitive status in the neuronal plasticity stimulation groups was significantly better than in the comparison group (p≤0.05. At a 6-month follow-up, there was a significant cognitive improvement in the combined stimulation group versus the drug-therapy and comparison groups (p≤0.05. Day-to-day activities and independent functioning also improved significantly more promptly in the patients receiving drug or combined therapies. More complex instrumental activities of daily living recovered significantly better during combined cognitive function stimulation than during pharmacological stimulation only. There was evidence that the drugs with proven stimulating effects on neuronal plasticity and nondrug cognitive training were effective in treating CI in the early recovery period of stroke. The combined drug and nondrug poststroke CI treatments reflecting the multimodal approach versus drug therapy were found to be most effective in these patients.
Full Text Available Aim: The main objective of this study was to analyse the development of cognitive functions and effect of cognitive rehabilitation on patients diagnosed with mild cognitive impairment (MCI, as a result of brain atrophy. Design: A quantitative non-randomized intervention study on a control sample of patients. Methods: The effect was observed in a group of patients ranging 59-91 years of age (N = 36. Only patients fulfilling the diagnostic criteria of mild cognitive disorder diagnosed by tomography (CT that had undergone 22 sessions, were involved in the clinical sample (n = 21. The control sample (n = 15 consisted of patients without any neurological diagnosis and who did not undergo cognitive sessions. Results: The effect of cognitive rehabilitation was measured by Addenbrooke's cognitive test, revised in 2010 (ACE-R; affective changes were measured by Beck´s scale of depression BDI-2 and by a scale used to detect anxiety and depression: the Hospital Anxiety and Depression Scale (HADS. Subjective change and improvement were observed using the Clinical Global Impression (CGI psychiatric scale. Changes in the functional state of patients were measured by means of the activities of daily living scale (ADL, including the instrumental version (IADL. The effect was examined in the form of entry and output tests, which were verified by statistical analysis, a significant level being p > 0.05. Conclusions: Significant differences in verbal tests and ACE-R were observed in the clinical sample of patients. Some significant changes were observed in the field of affective symptoms, according to the HADS and BDI-2. The clinical sample showed a significant improvement in subjective clinical state (CGI. The ADL and IADL questionnaires seem to have been inadequate for purpose due to their low sensitivity. The effect of cognitive rehabilitation in patients diagnosed with mild cognitive disorder can be seen and verified in comparison with the control sample
Bucholtz, Nina; Demuth, Ilja
While the pathogenesis of the sporadic form of Alzheimer disease (late onset Alzheimer disease, LOAD) is not fully understood, it seems to be clear that a combination of genetic and environmental factors are involved and influence the course of the disease. Among these factors, elevated levels of oxidative stress have been recognized and individual differences in the capacity to deal with DNA damage caused by its effects have been the subject of numerous studies. This review summarizes the research on DNA repair proteins and genes in the context of LOAD pathogenesis and its possible prodromal stage, mild cognitive impairment (MCI). The current status of the research in this field is discussed with respect to methodological issues which might have compromised the outcome of some studies and future directions of investigation on this subject are depicted.
Bocanegra, Yamile; García, Adolfo M; Lopera, Francisco; Pineda, David; Baena, Ana; Ospina, Paula; Alzate, Diana; Buriticá, Omar; Moreno, Leonardo; Ibáñez, Agustín; Cuetos, Fernando
Parkinson's disease (PD) patients show marked impairments in processing action verbs, and to a lesser extent, concrete (specially, manipulable) nouns. However, it is still unclear to what extent deficits in each of these categories are influenced by more general cognitive dysfunctions, and whether they are modulated by the words' implied motility. To examine these issues, we evaluated 49 non-demented PD patients and 49 healthy volunteers in an oral production task. The patients were divided into two groups depending on the presence or absence of mild cognitive impairment (PD-MCI and PD-nMCI, respectively). Participants named pictures of actions varying in motion content (low and high) and of objects varying in manipulability (low and high). The PD-MCI group showed deficits across all four categories. However, PD-nMCI patients exhibited a selective difficulty for high-motion action verbs. This finding corroborates and refines previous results suggesting that disturbances of action-related lexico-semantic information in PD constitute a sui generis alteration manifested early in the course of the disease's physiopathology. Moreover, it suggests that the grounding of action verbs on motor circuits could depend on fine-grained intracategorical semantic distinctions.
Shun-wei Li; Bin Peng; Hong Kong
Objective: To evaluate the P3 latency in OSAS patients ,snorers and nonsnore subjects and observe the emotional disturbance in OSAS patients. Backround: Neurobehavioral abnormalities are the most common nonrespiratory manifestations in OSAS. Impairment of cognitive functions, as well as emotional disturbances and abnormal P3 latency in OSAS have been documnerted. However, seldom studies were done on comparing the changes the P3 and memory function between OSAS patients and snorers, and the psychological scales of OSAS patients before and after CPAP treatrment Methods: For P3 and memory study, three groups: OSAS group, snorer group, and nosnorer group,21 sub jects each, were administered PSG, ERP and Clinical Memory Test All data were analyzed by General Linear Model; For psychological scales, 16 OSAS patients were tested by SAS,SDS,HRSD and HRSA. Two-tailed students t-test was used for data analysis. A value of p＜0.05 was considered statistically significant. Results: The P3 latency in OSAS patients were significant longer than that in snorers and nosnorers. There′s no signficant difference between snorers and norsnorers. No differerces in amplitude were seen among three groups. Scores of MQ and sulbtest FRP was higher than that ofOSAS group and nonsnorers group. Differences in MSO2 and SE among three groups were noticed. Twelve patients′ scores of SDS, SAS, HAMD and HAMA were beyond the normal range. The scores decreased significantly after three months treatment of CPAP. Discussion: Our study revealed the prolonged P3 latency with auditory evoked potential which indicated the impairment of cognitive function in OSAS patients. Deficits of memory were also documented in OSAS patients. As to our knowledge, snoreres were not exclude from controls subjects in many studies when compared with OSAS patient. In our study, data showed significant difference between srorers and nonsnore subjects in merb SO2 value although no difference was seen in the P3 latency. The
Sofis, Michael J; Jarmolowicz, David P; Kaplan, Sam V; Gehringer, Rachel C; Lemley, Shea M; Blagg, Brian S; Johnson, Michael A
Chemotherapy induced cognitive impairment (i.e. Chemobrain) involves acute and long-term deficits in memory, executive function, and processing speed. Animal studies investigating these cognitive deficits have had mixed results, potentially due to variability in the complexity of behavioral tasks across experiments. Further, common chemotherapy treatments such as 5-Fluorouracil (5-FU) break down myelin integrity corresponding to hippocampal neurodegenerative deficits and mitochondrial dysfunction. There is little evidence, however, of pharmacological treatments that may target mitochondrial dysfunction. Using a differential reinforcement of low rates (DRL) task combining spatial and temporal components, the current study evaluated the preventative effects of the pharmacological agent KU32 on the behavior of rats treated with 5-FU (5-FU+Saline vs. 5FU+KU32). DRL performance was analyzed the day after the first set of injections (D1), the day after the second set of injections (D7) and the last day of the experiment (D14). The 5FU+KU32 group earned significantly more reinforcers on the DRL task at D7 and D14 than the 5FU+Saline group. Further, the 5FU+KU32 group showed significantly better temporal discrimination. The 5FU+KU32 showed within-group improvement in temporal discrimination from D7 to D14. No significant differences were observed in spatial discrimination, however, those in the 5FU+Saline group responded more frequently on T3 compared to the 5FU+KU32 group, highlighting temporal discrimination differences between groups. The current data suggest that KU32 shows promise in the prevention of chemotherapy induced impairments in temporal discrimination.
Jeffrey R Petrella
Full Text Available BACKGROUND: Normal subjects deactivate specific brain regions, notably the posteromedial cortex (PMC, during many tasks. Recent cross-sectional functional magnetic resonance imaging (fMRI data suggests that deactivation during memory tasks is impaired in Alzheimer's disease (AD. The goal of this study was to prospectively determine the prognostic significance of PMC deactivation in mild cognitive impairment (MCI. METHODOLOGY/PRINCIPAL FINDINGS: 75 subjects (34 MCI, 13 AD subjects and 28 controls underwent baseline fMRI scanning during encoding of novel and familiar face-name pairs. MCI subjects were followed longitudinally to determine conversion to AD. Regression and analysis of covariance models were used to assess the effect of PMC activation/deactivation on conversion to dementia as well as in the longitudinal change in dementia measures. At longitudinal follow up of up to 3.5 years (mean 2.5+/-0.79 years, 11 MCI subjects converted to AD. The proportion of deactivators was significantly different across all groups: controls (79%, MCI-Nonconverters (73%, MCI-converters (45%, and AD (23% (p<0.05. Mean PMC activation magnitude parameter estimates, at baseline, were negative in the control (-0.57+/-0.12 and MCI-Nonconverter (-0.33+/-0.14 groups, and positive in the MCI-Converter (0.37+/-0.40 and AD (0.92+/-0.30 groups. The effect of diagnosis on PMC deactivation remained significant after adjusting for age, education and baseline Mini-Mental State Exam (p<0.05. Baseline PMC activation magnitude was correlated with change in dementia ratings from baseline. CONCLUSION: Loss of physiological functional deactivation in the PMC may have prognostic value in preclinical AD, and could aid in profiling subgroups of MCI subjects at greatest risk for progressive cognitive decline.
Full Text Available Neuropsychiatric symptoms or Behavioral and Psychological Symptoms of Dementia (BPSD are common and invariably appear at some point during the course of the disease, mediated both by cerebrovascular disease and neurodegenerative processes. Few studies have compared the profiles of BPSD in Vascular Cognitive Impairment (VCI of different subtypes (subcortical or cortical and clinical stages (Vascular Cognitive Impairment No Dementia [VaCIND] and Vascular Dementia [VaD].Objective:To review the BPSD associated with different subtypes and stages of VCI using the Neuropsychiatric Inventory (NPI.Methods:Medline, Scielo and Lilacs databases were searched for the period January 2000 to December 2014, with the key words: "BPSD AND Vascular Dementia, "NPI AND Vascular Dementia" and "NPI AND VCI. Qualitative analysis was performed on studies evaluating BPSD in VCI, using the Neuropsychiatric Inventory (NPI.Results:A total of 82 studies were retrieved of which 13 were eligible and thus included. Among the articles selected, 4 compared BPSD in Subcortical Vascular Dementia (SVaD versus Cortical-Subcortical Vascular Dementia (CSVaD, 3 involved comparisons between SVaD and VaCIND, 1 study analyzed differences between CSVaD and VaCIND, while 5 studies assessed BPSD in CSVaD. Subcortical and Cortical-Subcortical VaD were associated predominantly with Apathy and Depression. VaCIND may present fewer behavioral symptoms than VaD.Conclusion:The profile of BPSD differs for different stages of VCI. Determining the most prevalent BPSD in VCI subtypes might be helpful for improving early diagnosis and management of these symptoms.
Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya
Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring.
Tonkikh, A A; Carlen, P L
Impaired regulation of presynaptic intracellular calcium is thought to adversely affect synaptic plasticity and cognition in the aged brain. We studied presynaptic cytosolic and mitochondrial calcium (Ca) dynamics using axonally loaded Calcium Green-AM and Rhod-2 AM fluorescence respectively in young (2-3 months) and aged (23-26 months) CA3 to CA1 Schaffer collateral excitatory synapses in hippocampal brain slices from Fisher 344 rats. After a tetanus (100 Hz, 200 ms), the presynaptic cytosolic Ca peaked at approximately 10 s in the young and approximately 12 s in the aged synapses. Administration of the membrane permeant Ca chelator, bis (O-aminophenoxy)-ethane-N,N,N,N-tetraacetic acid (BAPTA-AM), significantly attenuated the Ca response in the aged slices, but not in the young slices. The presynaptic mitochondrial Ca signal was much slower, peaking at approximately 90 s in both young and aged synapses, returning to baseline by 300 s. BAPTA-AM significantly attenuated the mitochondrial calcium signal only in the young synapses. Uncoupling mitochondrial respiration by carbonyl cyanide m-chlorophenylhydrazone (CCCP) application evoked a massive intracellular cytosolic Ca increase and a significant drop of mitochondrial Ca, especially in aged slices wherein the cytosolic Ca signal disappeared after approximately 150 s of washout and the mitochondrial Ca signal disappeared after 25 s of washout. These signals were preserved in aged slices by BAPTA-AM. Five minutes of oxygen glucose deprivation (OGD) was associated with a significant increase in cytosolic Ca in both young and aged synapses, which was irreversible in the aged synapses. These responses were significantly attenuated by BAPTA-AM in both the young and aged synapses. These results support the hypothesis that increasing intracellular calcium neuronal buffering in aged rats ameliorates age-related impaired presynaptic Ca regulation.
Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang
Identification of subjects at the early stages of Alzheimer’s disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%–17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features. PMID:28243102
Rickenbach, Elizabeth Hahn; Condeelis, Kristen L; Haley, William E
Daily experiences of stress are common and have been associated with worse affect among older adults. People with mild cognitive impairment (PWMCI) have measurable memory deficits in between normal cognition and dementia and have been identified as having greater psychological distress than cognitively healthy older adults (CHOAs). Little is known about whether daily stressors contribute to distress among PWMCI. We hypothesized that compared with CHOAs, PWMCI would have higher daily negative affect and lower daily positive affect, report greater numbers and severity of daily stressors, and experience greater emotional reactivity to daily stressors. Fifteen clinically diagnosed PWMCI and 25 CHOAs completed daily reports of stressors, stressor severity, and positive and negative affect over an 8-day period. PWMCI reported higher daily negative affect, lower daily positive affect, and higher numbers and greater severity of memory stressors but did not differ from CHOAs in numbers or severity of general stressors. Cognitive status was a moderator of the daily stress-affect relationship. Days with greater numbers and severity of general daily stressors were associated with higher negative affect only for PWMCI. The numbers and severity of memory stressors were not associated with negative affect. In addition, more severe general daily stressors and memory stressors were associated with lower positive affect for all participants. Results suggest that PWMCI are less resilient in the face of daily stress than are CHOAs in terms of negative affect, perhaps because of declines in reserve capacity. The study presents a promising approach to understanding stress and coping in predementia states of cognition.
Alahmadi, Hanin H.; Shen, Yuan; Fouad, Shereen; Luft, Caroline Di B.; Bentham, Peter; Kourtzi, Zoe; Tino, Peter
Early diagnosis of dementia is critical for assessing disease progression and potential treatment. State-or-the-art machine learning techniques have been increasingly employed to take on this diagnostic task. In this study, we employed Generalized Matrix Learning Vector Quantization (GMLVQ) classifiers to discriminate patients with Mild Cognitive Impairment (MCI) from healthy controls based on their cognitive skills. Further, we adopted a “Learning with privileged information” approach to combine cognitive and fMRI data for the classification task. The resulting classifier operates solely on the cognitive data while it incorporates the fMRI data as privileged information (PI) during training. This novel classifier is of practical use as the collection of brain imaging data is not always possible with patients and older participants. MCI patients and healthy age-matched controls were trained to extract structure from temporal sequences. We ask whether machine learning classifiers can be used to discriminate patients from controls and whether differences between these groups relate to individual cognitive profiles. To this end, we tested participants in four cognitive tasks: working memory, cognitive inhibition, divided attention, and selective attention. We also collected fMRI data before and after training on a probabilistic sequence learning task and extracted fMRI responses and connectivity as features for machine learning classifiers. Our results show that the PI guided GMLVQ classifiers outperform the baseline classifier that only used the cognitive data. In addition, we found that for the baseline classifier, divided attention is the only relevant cognitive feature. When PI was incorporated, divided attention remained the most relevant feature while cognitive inhibition became also relevant for the task. Interestingly, this analysis for the fMRI GMLVQ classifier suggests that (1) when overall fMRI signal is used as inputs to the classifier, the post
Hanin Hamdan Alahmadi
Full Text Available Early diagnosis of dementia is critical for assessing disease progression and potential treatment. State-or-the-art machine learning techniques have been increasingly employed to take on this diagnostic task. In this study, we employed Generalised Matrix Learning Vector Quantization (GMLVQ classifiers to discriminate patients with Mild Cognitive Impairment (MCI from healthy controls based on their cognitive skills. Further, we adopted a ``Learning with privileged information'' approach to combine cognitive and fMRI data for the classification task. The resulting classifier operates solely on the cognitive data while it incorporates the fMRI data as privileged information (PI during training. This novel classifier is of practical use as the collection of brain imaging data is not always possible with patients and older participants.MCI patients and healthy age-matched controls were trained to extract structure from temporal sequences. We ask whether machine learning classifiers can be used to discriminate patients from controls based on the learning performance and whether differences between these groups relate to individual cognitive profiles. To this end, we tested participants in four cognitive tasks: working memory, cognitive inhibition, divided attention, and selective attention. We also collected fMRI data before and after training on the learning task and extracted fMRI responses and connectivity as features for machine learning classifiers. Our results show that the PI guided GMLVQ classifiers outperform the baseline classifier that only used the cognitive data. In addition, we found that for the baseline classifier, divided attention is the only relevant cognitive feature. When PI was incorporated, divided attention remained the most relevant feature while cognitive inhibition became also relevant for the task. Interestingly, this analysis for the fMRI GMLVQ classifier suggests that (1 when overall fMRI signal for structured stimuli is
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.
Yang, Fengying; Chu, Xiaolei; Yin, Miaomiao; Liu, Xiaolei; Yuan, Hairui; Niu, Yanmei; Fu, Li
Defect of autophagy is common to many neurodegenerative disorders because it serves as a major degradation pathway for the clearance of various aggregate-prone proteins. Mammalian target of rapamycin (mTOR) signaling, which is recognized as the most important negative regulator of autophagy, is also involved in neurodegenerative diseases. However, the role of mTOR and its dependent autophagy in normal brain during aging remains unknown. Furthermore, caloric restriction (CR) is frequently used as a tool to study mechanisms behind aging and age-associated diseases because CR can prevent age-related diseases and prolong lifespan in several model organisms. Inhibiting mTOR and promoting autophagy activity play roles in aging delayed by CR. However, whether CR can ameliorate age-related cognition deficits by inhibiting mTOR and activate autophagy in hippocampus needs to be further investigated. Here we showed a decline of autophagic degradation in mice hippocampus in correlation with age-dependent cognitive dysfunction, whereas the activity of mTOR and its upstream brain-derived neurotrophic factor (BDNF)/phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling was decreased with aging. In addition, facilitating the mTOR pathway successfully declines and sustains autophagic degradation with aging in hippocampus by CR treatment and is involved in CR by ameliorating age-related cognitive deficits.
Soo Ryon Kim
Full Text Available The aims of this study were to investigate concrete and abstract word definition ability (1 between patients with amnestic mild cognitive impairment (aMCI and normal adults and (2 between the aMCI subtypes (i.e., amnestic single-domain MCI and amnestic multidomain MCI; asMCI and amMCI and normal controls. The 68 patients with aMCI (29 asMCI and 39 amMCI and 93 age- and education-matched normal adults performed word definition tasks composed of five concrete (e.g., train and five abstract nouns (e.g., jealousy. Task performances were analyzed on total score, number of core meanings, and number of supplementary meanings. The results were as follows. First, the aMCI patients scored significantly poorer than the normal controls in only abstract word definition. Second, both subtypes of aMCI performed worse than the controls in only abstract word definition. In conclusion, a definition task of abstract rather than concrete concepts may provide richer information to show semantic impairment of aMCI.
Patricia A Boyle
Full Text Available Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer's disease or mild cognitive impairment.Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams.Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p's<0.001. Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment.Poor decision making is a consequence of cognitive decline among older persons without Alzheimer's disease or mild cognitive impairment, those widely considered "cognitively healthy." These findings suggest
Leela Narayanan; Alison Dorothy Murray
Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socioeconomic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer’s disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging(MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18 F fluoro-deoxy glucose positron emission tomography(PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.
Ren, Xiaojia; St Clair, Daret K; Butterfield, D Allan
One of the major complaints patients who survive cancer often make is chemotherapy induced cognitive impairment (CICI), which survivors often call "chemo brain." CICI is a side effect of chemotherapy due to the cytotoxicity and neurotoxicity of anti-cancer drugs causing structural and functional changes in brain, even when drugs that do not cross the blood brain barrier (BBB) are used. Diminished cognitive functions including diminution of learning and memory, concentration and attention, processing speed and executive functions that reduce quality of life and ability to work are common signs and symptoms of CICI. There still is not a clarified and complete mechanism for CICI, but researchers have pointed to several biochemical candidates. Chemotherapy-induced, cytokine-mediated involvement in CICI will be mainly discussed in this review paper with emphasis on different types of cytokines, correlated with BBB and epigenetic changes. Mechanisms of ROS-generating, anti-cancer drugs and their relation to cytokine-mediated CICI will be emphasized.
Full Text Available Abstract Background Adolescent idiopathic scoliosis is characterized by a three-dimensional deviation of the vertebral column and its etiopathogenesis is unknown. Various factors cause idiopathic scoliosis, and among these a prominent role has been attributed to the vestibular system. While the deficits in sensorimotor transformations have been documented in idiopathic scoliosis patients, little attention has been devoted to their capacity to integrate vestibular information for cognitive processing for space perception. Seated idiopathic scoliosis patients and control subjects experienced rotations of different directions and amplitudes in the dark and produced saccades that would reproduce their perceived spatial characteristics of the rotations (vestibular condition. We also controlled for possible alteration of the oculomotor and vestibular systems by measuring the subject's accuracy in producing saccades towards memorized peripheral targets in absence of body rotation and the gain of their vestibulo-ocular reflex. Results Compared to healthy controls, the idiopathic scoliosis patients underestimated the amplitude of their rotations. Moreover, the results revealed that idiopathic scoliosis patients produced accurate saccades to memorized peripheral targets in absence of body rotation and that their vestibulo-ocular reflex gain did not differ from that of control participants. Conclusion Overall, results of the present study demonstrate that idiopathic scoliosis patients have an alteration in cognitive integration of vestibular signals. It is possible that severe spine deformity developed partly due to impaired vestibular information travelling from the cerebellum to the vestibular cortical network or alteration in the cortical mechanisms processing the vestibular signals.
Mitolo, Micaela; Gardini, Simona; Fasano, Fabrizio; Crisi, Girolamo; Pelosi, Annalisa; Pazzaglia, Francesca; Caffarra, Paolo
Spatial abilities decline in normal aging and decrease faster and earlier in Alzheimer's disease (AD), but these deficits are under investigated. The main goals of this study were to assess visuospatial memory abilities in mild cognitive impairment (MCI), in order to verify whether these tasks might be valid as the standard cognitive test to differentiate MCI individuals from normal controls and to investigate the brain structural correlates of visuospatial deficits. Twenty MCI patients and fourteen healthy elderly controls underwent an experimental visuospatial battery, which also included self-rating spatial questionnaires, and structural MRI brain imaging. Compared to healthy elderly controls, MCI patients scored significantly worse in almost all visuospatial tasks. ROC analysis showed that visuospatial tasks had an elevated discriminant power between groups (AUC >0.90). Voxel-based morphometry analysis, compared to controls, disclosed a higher level of atrophy in frontal and medio-temporal regions and a different pattern of correlation between grey matter values and visuospatial performance, with wider distributed areas of the occipital and middle temporal cortex in the map and route learning. This study indicates that visuospatial memory tests are valid tools in completing the diagnostic evaluation of MCI.
Kiddoe, Jared M; Whitfield, Keith E; Andel, Ross; Edwards, Christopher L
This article compared and contrasted the Telephone Interview of Cognitive Status (TICS) to the racially-sensitive Short Portable Mental Status Questionnaire (SPMSQ). The empirical questions addressed was whether the TICS over-represented African American (AA) cognitive impairment (CI) relative to the SPMSQ, if there were age differences in CI prevalence between younger subjects (ages 50-64) and older ones (>64 years) and on accuracy to detect CI in individuals with higher levels of educations (> or =13 years) versus those with lower education levels (TICS at 45.0%. Within the younger group, TICS and CI prevalence was 49.3 and 80% among the older group. Within the younger group SPMSQ and CI prevalence was 14.5 and 53.8% among the older group. Within the higher educated group, TICS and CI prevalence was 36.7 and 51.4% among the lower educated. Within the higher educated group, SPMSQ and CI prevalence was 7.7 and 14.5% among the lower educated. Findings are consistent with our hypotheses that the TICS would be a less accurate assessor of CI among AAs.
Selnes, Per; Grambaite, Ramune; Rincon, Mariano; Bjørnerud, Atle; Gjerstad, Leif; Hessen, Erik; Auning, Eirik; Johansen, Krisztina; Almdahl, Ina S; Due-Tønnessen, Paulina; Vegge, Kjetil; Bjelke, Börje; Fladby, Tormod
To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-β concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-β concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.
Full Text Available Crystal C Watkins,1,2 Glenn J Treisman2 1The Memory Center in Neuropsychiatry, Sheppard Pratt Health System, 2Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression, minor cognitive-motor dysfunction, and HIV-associated dementia. Keywords: HIV, delirium, depression, HAND, dementia; HIV-associated neurocognitive disorder
B. A. Abusueva
Full Text Available Background. Cognitive disorders may often lead to professional invalidisation and increasing dependence on the external assistance in every day life. Identification of patients with preserved intellectual status and social adaptation but with mild cognitive impairment (MCI is considered to be an effective measure. MCI detection and timely initiation of treatment in most patients is essential to delay the onset of severe dementia.Objective. Investigating influence of Cellex in patients with chronic cerebral ischemia and MCI.Materials and methods. As a part of non-interventional observational comparative study we evaluated the results of Cellex administration in 90 patients with MCI. Patients were divided into 2 groups. Patients from both groups received 1 course of 10 subcutaneous injections of Cellex drug at the dose of 1 mL, and patients from group 2 received two identical courses with an interval of two months. The survey, which included psychometric testing by using special questionnaires (Mini-Mental State Examination, “Frontal Assessment Battery” and “Clock Drawing” tests, Schulte test was performed before treatment, and at months 1 and 2 after its completion.Results. Neuropsychological examination revealed improvement in the patients state, more pronounced after the 2nd course of therapy.Discussion. Our results provide a basis for using Cellex in patients with chronic cerebral ischemia and MCI, allowing to proceede with further studies on the optimal dosage of that drug.
Full Text Available Sandor Balsamo,1–4 Jeffrey M Willardson,5 Frederico Santos de Santana,1–4 Jonato Prestes,6 Denise Coscrato Balsamo,4 Dahan da Cunha Nascimento,3–6 Leopoldo dos Santos-Neto,1,2 Otávio T Nobrega1 1Graduate Program in Medical Sciences, School of Medicine, University of Brasília, 2Rheumatology Division, University of Brasília Hospital, 3Department of Physical Education, Euro-American University Center, 4GEPEEFS (Strength Training and Health Research Group, Brasília, Brazil; 5Kinesiology and Sports Studies Department, Eastern Illinois University, Charleston, IL, USA; 6Graduate Program in Physical Education and Health, Catholic University of Brasilia, Brasilia, Brazil Abstract: Physical activity has a protective effect on brain function in older people. Here, we briefly reviewed the studies and results related to the effects of exercise on cognitive impairment and Alzheimer's disease. The main findings from the current body of literature indicate positive evidence for structured physical activity (cardiorespiratory and resistance exercise as a promising non-pharmacological intervention for preventing cognitive decline. More studies are needed to determine the mechanisms involved in this preventative effect, including on strength, cardiorespiratory, and other types of exercise. Thus, the prevention of Alzheimer's disease may depend on healthy lifestyle habits, such as a structured physical fitness program. Keywords: randomized controlled trial, memory disorders, healthy lifestyle habits, physical activity
Wittich, Walter; Phillips, Natalie; Nasreddine, Ziad S.; Chertkow, Howard
Evaluating the cognitive status of individuals who are visually impaired is limited by the design of the test that is used. This article presents data on the sensitivity and specificity of the version of the Montreal Cognitive Assessment for people who are visually impaired. The original validation data were reanalyzed, excluding the five visual…
Heyl, Vera; Wahl, Hans-Werner
This article reports on a study that investigated the role of cognitive resources in the everyday functioning of 121 older adults who were visually impaired and 150 sighted older adults, with a mean age of 82 years. Cognitive performance and everyday functioning were most strongly related in the group who were visually impaired. The authors…
Zhang, Jiabei; Piwowar, Nathan; Reilly, Coleen Jennifer
The purpose of this investigation was to analyze the physical fitness performance of young adults with and without cognitive impairments. Participants were 75 young adults, including 41 without disabilities (23 females, 18 males; M of age = 21.88) and 34 with mild cognitive impairments (14 females, 20 males; M of age = 21.79). They received…
25-hydroxyvitamin D (25[OH]D) deficiency and cognitive impairment are both prevalent in hemodialysis patients in the United States. This study tested the hypothesis that 25(OH)D deficiency may be associated with cognitive impairment because of its vasculoprotective, neuroprotective, and immune-modul...
Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold;
To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly.......To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly....
Litvan, I.; Goldman, J.G.; Tröster, A.I.; Schmand, B.A.; Weintraub, D.; Petersen, R.C.; Mollenhauer, B.; Adler, C.H.; Marder, K.; Williams-Gray, C.H.; Aarsland, D.; Kulisevsky, J.; Rodriguez-Oroz, M.C.; Burn, D.J.; Barker, R.A.; Emre, M.
Mild cognitive impairment is common in nondemented Parkinson's disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic cr
Bin Peng; Shun-wei Li; Hong Kang; Xi-zhen Huang
Objective To evaluate the emotional and cognitive status in patients with obstructive sleep apnea syndrome (OSAS),using neuropsychological tests and evoked-related potential (P3).Methods Sixteen patients diagnosed of OSAS were tested by Hamilton rating scale for anxiety (HRSA) and Hamilton rating scale for depression (HRSD). Other three groups, OSAS patient group (n = 21), snoring group (n = 21), and control group (n = 21), were administered polysomnography (PSG), auditory evoked event-related potential (P3), and clinic memory test. The results were analyzed using general linear model (GLM) analysis and Post Hoc test.Results Twelve OSAS patients' scores of HRSA and HRSD were beyond the normal range, 26.42 ± 4.48 and 22.08 ±3.97 respectively. The auditory P3 latency in OSAS group was 363.1 ± 22.9 ms (Fz), 368.57 ± 28.03 ms (Cz), in snoring group 336.57 ± 31.08 ms (Fz), 339.81 ± 31.76 ms (Cz), in control group 340.8 ± 28.7 ms (Fz), 338.29 ± 29.21 ms (Cz).There were significant differences between OSAS group and snoring group, as well as control group (P ＜ 0.05). No significant difference was seen between snoring group and control group. No significant difference was noted in P3 amplitude among three groups. Memory quotient (MQ) reduced in snoring group compared with control group.Conclusions Emotional disturbances are common clinical features in OSAS patients. Abnormal auditory P3 latency indicates the cognitive dysfunction in OSAS patients. Nocturnal hypoxaemia may play an important role on it. Snorers should be monitored because of the tendency to develop cognitive impairment.
Full Text Available Cognitive impairment is one of the most crucial disorders among multiple sclerosis (MS patients. Since MS is an inflammatory disease and Boswellia papyrifera has anti-inflammatory effects, the influence of B. papyrifera on cognitive impairment in MS patients has been investigated in the present study.In this clinical trial, 80 MS patients who referred to the clinic of Shafa Hospital, Kerman, Iran were selected. Having completed a written consent form, patients with relapsing remitting MS, with no occurrence of a new attack throughout 1 month before the study, with no pregnancy or breastfeeding entered the study. The patients were randomly divided into two groups; then Brief International Cognitive Assessment for MS (BICAMS test was carried out. One group received B. papyrifera (capsule 300 mg, twice a day while the other group received placebo with the same dose for 2 months. After 2 months of treatment, BICAMS was redone and changes were analyzed. The significant change value on the before-after BICAMS points were considered to be 8, 13, and 7 points for the symbol digit modality test (SDMT, the California verbal learning test (CVLT, and the brief visual-spatial memory test revised (BVMT-R, respectively.The patients' mean age was 36.58 8.50 years. The mean duration of disease was 7.41 4.13 years. About 84.2% (n = 64 of the patients was female. In the BVMT-R, 13 patients (34.2%, who had already taken B. papyrifera, were shown to have significant improvement compared to the placebo group with no improvement (P < 0. 001. About 12 and 8 patients in the treatment and placebo groups in the SDMT, respectively (P = 0.200 and 17 and 12 patients in the treatment and placebo groups in the CVLT, respectively (P = 0.170 had significant change values.B. papyrifera showed significant improvement in visuospatial memory, but had no effect on verbal memory and information processing speed.
Full Text Available We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158 completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition five months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests.
Bertrams, Alex; Baumeister, Roy F; Englert, Chris
We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests.
Early psychological theories of autism explained the clinical features of this condition in terms of perceptual and sensory processing impairments. The arrival of domain-specific social cognitive theories changed this focus, postulating a 'primary' and specific psychological impairment of social cognition. Across the years, evidence has been growing in support of social cognitive and social attention explanations in autism. However, there has also been evidence for general non-social cognitive impairments in representational understanding, attention allocation and sensory processing. Here, I review recent findings and consider the case for the specificity and primacy of the social cognitive impairment, proposing that we should focus more explicitly on clinically valid features for insights on the integration of 'social' and 'non-social' cognition.
Mine, Masashi; Miyata, Kimie; Morikawa, Masayuki; Nishi, Tomo; Okamoto, Nozomi; Kawasaki, Ryo; Yamashita, Hidetoshi; Kurumatani, Norio; Ogata, Nahoko
Both visual impairment and cognitive impairment are essential factors that determine the quality of life in the aged population. The aim of this study was to determine if a correlation existed between visual acuity and cognitive impairment in an elderly Japanese population. The Fujiwara-kyo Eye Study was a cross-sectional study of individuals aged ≥68 years who lived in Nara Prefecture of Japan. Participants underwent ophthalmological examinations and cognitive function test. A mild visual impairment was defined as having a best corrected visual acuity (BCVA) >0.2 logarithm of the minimum angle of resolution (logMAR) units in the better eye. Cognitive impairment was defined as having a Mini-Mental State Examination (MMSE) score of ≤23 points. A total to 2818 individuals completed the examinations. The mean age of the participants was 76.3 ± 4.8 years (mean ± standard deviation). The mean BCVA of the better eye was -0.02 ± 0.13 logMAR units and 6.6% subjects were classified as being mildly visually impaired. The mean MMSE score was 27.3 ± 2.3 and 5.7% subjects were classified as being cognitively impaired. The proportion of subjects with cognitive or moderate visual impairment increased with age, and there was a significant correlation between the visual acuity and MMSE score (r = -0.10, p < 0.0001). Subjects with mild visual impairments had 2.4 times higher odds of having cognitive impairment than those without visual impairment (odds ratio 2.4, 95% confidence interval, 1.5-3.8, p < 0.001) after adjusting for age, sex, and length of education. We conclude that it may be important to maintain good visual acuity to reduce the risk of having cognitive impairment.
Mine, Masashi; Miyata, Kimie; Morikawa, Masayuki; Nishi, Tomo; Okamoto, Nozomi; Kawasaki, Ryo; Yamashita, Hidetoshi; Kurumatani, Norio; Ogata, Nahoko
Abstract Both visual impairment and cognitive impairment are essential factors that determine the quality of life in the aged population. The aim of this study was to determine if a correlation existed between visual acuity and cognitive impairment in an elderly Japanese population. The Fujiwara-kyo Eye Study was a cross-sectional study of individuals aged ≥68 years who lived in Nara Prefecture of Japan. Participants underwent ophthalmological examinations and cognitive function test. A mild visual impairment was defined as having a best corrected visual acuity (BCVA) >0.2 logarithm of the minimum angle of resolution (logMAR) units in the better eye. Cognitive impairment was defined as having a Mini-Mental State Examination (MMSE) score of ≤23 points. A total to 2818 individuals completed the examinations. The mean age of the participants was 76.3 ± 4.8 years (mean ± standard deviation). The mean BCVA of the better eye was −0.02 ± 0.13 logMAR units and 6.6% subjects were classified as being mildly visually impaired. The mean MMSE score was 27.3 ± 2.3 and 5.7% subjects were classified as being cognitively impaired. The proportion of subjects with cognitive or moderate visual impairment increased with age, and there was a significant correlation between the visual acuity and MMSE score (r = −0.10, p < 0.0001). Subjects with mild visual impairments had 2.4 times higher odds of having cognitive impairment than those without visual impairment (odds ratio 2.4, 95% confidence interval, 1.5–3.8, p < 0.001) after adjusting for age, sex, and length of education. We conclude that it may be important to maintain good visual acuity to reduce the risk of having cognitive impairment. PMID:27610269
Downey, Laura E.; Mahoney, Colin J.; Buckley, Aisling H.; Golden, Hannah L.; Henley, Susie M.; Nicole Schmitz; Schott, Jonathan M.; Simpson, Ivor J.; Sebastien Ourselin; Fox, Nick C.; Sebastian J. Crutch; Warren, Jason D.
Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progre...
Full Text Available Abstract Background Differentiating amnestic mild cognitive impairment (aMCI from normal cognition is difficult in clinical settings. Self-reported and informant-reported memory complaints occur often in both clinical groups, which then necessitates the use of a comprehensive neuropsychological examination to make a differential diagnosis. However, the ability to identify cognitive symptoms that are predictive of aMCI through informant-based information may provide some clinical utility in accurately identifying individuals who are at risk for developing Alzheimer's disease (AD. Methods The current study utilized a case-control design using data from an ongoing validation study of the Alzheimer's Questionnaire (AQ, an informant-based dementia assessment. Data from 51 cognitively normal (CN individuals participating in a brain donation program and 47 aMCI individuals seen in a neurology practice at the same institute were analyzed to determine which AQ items differentiated aMCI from CN individuals. Results Forward stepwise multiple logistic regression analysis which controlled for age and education showed that 4 AQ items were strong indicators of aMCI which included: repetition of statements and/or questions [OR 13.20 (3.02, 57.66]; trouble knowing the day, date, month, year, and time [OR 17.97 (2.63, 122.77]; difficulty managing finances [OR 11.60 (2.10, 63.99]; and decreased sense of direction [OR 5.84 (1.09, 31.30]. Conclusions Overall, these data indicate that certain informant-reported cognitive symptoms may help clinicians differentiate individuals with aMCI from those with normal cognition. Items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power.
Full Text Available In recent decades, several pharmacological strategies have been developed to prevent age-related cognitive impairment. However, the ineffectiveness of the majority of these strategies has led to growing interest in behavioural intervention. Cognitive stimulation and physical activity have been shown to provide significant benefits by counteracting cognitive impairment and dementia. Animal models have provided information on the neurobiological mechanisms that mediate the formation of cognitive and brain reserve. This paper reviews several studies on aged rodents showing the positive effects of environmental enrichment and aerobic exercise on brain and cognitive function of these animals. The implications of this research for human aging is discussed.
Olsen, Line; Rasmussen, Henrik B; Hansen, Thomas;
The estrogen receptor alpha (ESR1) gene has been implicated in the process of cognitive impairment in elderly women. In a paired case-control study, we tested whether two ESR1 gene polymorphisms (the XbaI and PvuII sites) are risk factors for cognitive impairment as measured by the six......-item Orientation-Memory-Concentration test in postmenopausal Danish women. Hormone replacement therapy, age and executive cognitive ability were examined as covariates for ESR1 gene effects on cognitive impairment. The XbaI polymorphism showed a marginal effect on cognitive abilities (P=0.054) when adjusted...... cognitive ability. These data support that the ESR1 gene variants affect cognitive functioning in postmenopausal women....
Serpa, R.F.B. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil)]. E-mail: email@example.com; Jesus, E.F.O. de [University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Anjos, M.J. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Lopes, R.T. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); Carmo, M.G.T. do [Federal University of Rio de Janeiro, Nutrition Institute, RJ (Brazil); Rocha, M.S. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Rodrigues, L.C. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Moreira, S. [University of Campinas State, Civil Engineering Department, SP (Brazil); Martinez, A.M.B. [Federal University of Rio de Janeiro, Department of Histology and Embryology, RJ (Brazil)
In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied.
Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study.
Visser, P.J.; Verhey, F.; Knol, D.L.; Scheltens, P.; Wahlund, L.O.; Freund-Levi, Y.; Tsolaki, M.; Minthon, L.; Wallin, A.K.; Hampel, H.; Burger, K.; Pirttila, T.; Soininen, H.; Olde Rikkert, M.G.M.; Verbeek, M.M.; Spiru, L.; Blennow, K.
BACKGROUND: Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is charact
K. M. Volkers
Full Text Available Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This cross-sectional study included 134 people with a mild to severe cognitive impairment (mean age 82 years. Multiple linear regression was performed, after controlling for covariates and the level of global cognition, with the performances on mobility, strength, aerobic fitness, and balance as predictors and working memory and episodic memory as dependent variables. Results. The full models explain 49–57% of the variance in working memory and 40–43% of episodic memory. Strength, aerobic fitness, and balance are significantly associated with working memory, explaining 3–7% of its variance, irrespective of the severity of the cognitive impairment. Physical performance is not related to episodic memory in older people with mild to severe cognitive impairment. Conclusions. Physical performance is associated with working memory in older people with cognitive impairment. Future studies should investigate whether physical exercise for increased physical performance can improve cognitive functioning. This trial is registered with ClinicalTrials.gov NTR1482.
Full Text Available Qiumei Wang,1 Zhenxin Zhang,2 Ling Li,2 Hongbo Wen,2 Qun Xu3,4 1Department of Geriatrics, 2Department of Neurology, 3School of Basic Medicine, Peking Union Medical College Hospital, 4Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: Although Parkinson's disease (PD is clinically characterized by motor symptoms, cognitive impairment is one of the most disabling non-motor symptoms. Despite it attracting increasing attention worldwide, less is known about its prevalence in the Chinese population. The objective of this study was to assess cognitive impairment and related risk factors in Chinese PD patients. Methods: We collected the demographic, diagnostic, and treatment information of 901 PD patients from 42 centers throughout the People's Republic of China, then administered a battery of neuropsychological tests, to assess motor, cognitive, and neuropsychiatric symptoms. Results: Overall, 193 of 901 (21.4% PD patients met the criteria for dementia (PD-D, and 206 (22.8% met the criteria for mild cognitive impairment (PD-MCI. Visuospatial dysfunction and attention/executive impairment predominated. Increased severity of cognitive impairment was associated with greater motor impairment. Patients with psychiatric symptoms, such as depression and hallucinations, were more likely to have dementia. Potentially, the younger-aged and more educated are shown less cognitive impairment, but age at onset, and levodopa equivalent dose, were not associated with the presence of cognitive dysfunction. Conclusion: The prevalence and profile of cognitive impairment in Chinese PD patients, as well as the risk factors, are similar as those reported for other races, but the frequency of nonamnestic cognitive domains differs. Keywords: cognitive impairment, risk factor, prevalence, Parkinson's disease
Full Text Available Introduction. Patients with dementia, especially Alzheimer’s disease, present several circadian impairments related to an accelerated perturbation of their biological clock that is caused by the illness itself and not merely age-related. Thus, the objective of this work was to elucidate whether these circadian system alterations were already present in patients with mild cognitive impairment (MCI, as compared to healthy age-matched subjects. Methods. 40 subjects (21 patients diagnosed with MCI, 74.1 ± 1.5 y.o., and 19 healthy subjects, 71.7 ± 1.4 y.o. were subjected to ambulatory monitoring, recording wrist skin temperature, motor activity, body position, and the integrated variable TAP (including temperature, activity, and position for one week. Nonparametrical analyses were then applied. Results. MCI patients exhibited a significant phase advance with respect to the healthy group for the following phase markers: temperature M5 (mean ± SEM: 04:20 ± 00:21 versus 02:52 ± 00:21 and L10 (14:35 ± 00:27 versus 13:24 ± 00:16 and TAP L5 (04:18 ± 00:14 versus 02:55 ± 00:30 and M10 (14:30 ± 00:18 versus 13:28 ± 00:23. Conclusions. These results suggest that significant advances in the biological clock begin to occur in MCI patients, evidenced by an accelerated aging of the circadian clock, as compared to a healthy population of the same age.
Full Text Available Takao Yamasaki,1,2 Shozo Tobimatsu1 1Department of Clinical Neurophysiology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 2Department of Neurology, Minkodo Minohara Hospital, Fukuoka, Japan Abstract: Alzheimer's disease (AD, Lewy body disease (LBD, and frontotemporal lobar degeneration (FTLD are three major types of neurodegenerative dementia. Intervention and treatment differ significantly among these major dementias, necessitating early and accurate diagnosis. Patients with AD, LBD, and FTLD exhibit specific patterns of visual dysfunction as early behavioral signs. These visual impairments are the manifestations of topographic patterns of neuropathology specific to each type of dementia. Electrophysiological measurements, such as visual evoked potentials and event-related potentials, are objective and noninvasive tools that can detect subtle functional changes in human brain. Therefore, with the use of visual evoked potentials and event-related potentials, early detection of specific patterns of visual dysfunction may be useful for differential diagnosis of dementia. In this review, we first summarize current knowledge about the relevant aspects of the human visual system. Second, we outline clinical characteristics, including visual perceptual abnormalities, of each type of degenerative dementia. Finally, we describe the application of visual evoked potential and event-related potential recording techniques to study visual perception in patients with mild cognitive impairment (prodromal stage of dementia. We stress that electrophysiological signals have potential as reliable biomarkers in the diagnosis of different types of dementia, especially in the case of overlapping phenotypes. Keywords: Alzheimer's disease, Lewy body disease, frontotemporal lobar degeneration, visual evoked potentials, event-related potentials, parallel visual pathways
Li, Yang; Wee, Chong-Yaw; Jie, Biao; Peng, Ziwen; Shen, Dinggang
Brain connectivity network derived from functional magnetic resonance imaging (fMRI) is becoming increasingly prevalent in the researches related to cognitive and perceptual processes. The capability to detect causal or effective connectivity is highly desirable for understanding the cooperative nature of brain network, particularly when the ultimate goal is to obtain good performance of control-patient classification with biological meaningful interpretations. Understanding directed functional interactions between brain regions via brain connectivity network is a challenging task. Since many genetic and biomedical networks are intrinsically sparse, incorporating sparsity property into connectivity modeling can make the derived models more biologically plausible. Accordingly, we propose an effective connectivity modeling of resting-state fMRI data based on the multivariate autoregressive (MAR) modeling technique, which is widely used to characterize temporal information of dynamic systems. This MAR modeling technique allows for the identification of effective connectivity using the Granger causality concept and reducing the spurious causality connectivity in assessment of directed functional interaction from fMRI data. A forward orthogonal least squares (OLS) regression algorithm is further used to construct a sparse MAR model. By applying the proposed modeling to mild cognitive impairment (MCI) classification, we identify several most discriminative regions, including middle cingulate gyrus, posterior cingulate gyrus, lingual gyrus and caudate regions, in line with results reported in previous findings. A relatively high classification accuracy of 91.89 % is also achieved, with an increment of 5.4 % compared to the fully-connected, non-directional Pearson-correlation-based functional connectivity approach.
Munro, Catherine E.; Donovan, Nancy J.; Guercio, Brendan J.; Wigman, Sarah E.; Schultz, Aaron P.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.
Background Neuropsychiatric symptoms (NPS), such as apathy and depression, commonly accompany cognitive and functional decline in early Alzheimer’s disease (AD). Prior studies have shown associations between affective NPS symptoms and neurodegeneration of medial frontal and inferior temporal regions in mild cognitive impairment (MCI) and AD dementia. Objective To investigate the association between functional connectivity in four brain networks and NPS in elderly with MCI. Methods NPS were assessed using the Neuropsychiatric Inventory in 42 subjects with MCI. Resting-state functional connectivity in four networks (default mode network, fronto-parietal control network (FPCN), dorsal attention network, and ventral attention network) was assessed using seed-based magnetic resonance imaging. Factor analysis was used to identify two factors of NPS: Affective and Hyperactivity. Linear regression models were utilized with the neuropsychiatric factors as the dependent variable and the four networks as the predictors of interest. Covariates included age, sex, premorbid intelligence, processing speed, memory, head movement, and signal-to-noise ratio. These analyses were repeated with the individual items of the Affective factor, using the same predictors. Results There was a significant association between greater Affective factor symptoms and reduced FPCN connectivity (p=0.03). There was no association between the Hyperactivity factor and any of the networks. Secondary analyses revealed an association between greater apathy and reduced FPCN connectivity (p=0.005), but none in other networks. Conclusions Decreased connectivity in the FPCN may be associated with greater affective symptoms, particularly apathy, early in AD. These findings extend prior studies, using different functional imaging modalities in individuals with greater disease severity. PMID:25854929
Uffelen, J.G.Z. van; Chinapaw, M.J.M.; Mechelen, W. van; Hopman-Rock, M.
Objective: To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI). Design: Randomised placebo-controlled trial. Setting: General community. Participants: Community-dwelling adults aged 70-80 with MCI. Interve
Abdel-Salam, Omar M E; El-Sayed El-Shamarka, Marwa; Salem, Neveen A; El-Mosallamy, Aliaa E M K; Sleem, Amany A
Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice.
Langdon, Kristopher D.; Granter-Button, Shirley; Carolyn W Harley; Moody-Corbett, Frances; Peeling, James; Corbett, Dale
Dementia is a major cause of morbidity in the western society. Pharmacological therapies to delay the progression of cognitive impairments are modestly successful. Consequently, new therapies are urgently required to improve cognitive deficits associated with dementia. We evaluated the effects of physical and cognitive activity on learning and memory in a rat model of vascular dementia (VasD). Male Sprague-Dawley rats (6 months old) were exposed to either regular chow or a diet rich in satura...
Khojasteh, F.; Nahavandi, A.; Mehrpouya, S.; Homberg, J.R.; Mirzamohammadi, S.; Raufi, S.; Soleimani, M.; Barati, M.
There is a strong link between cognitive impairment and depression, but up to date it is not clear whether cognitive impairment is 'cause' or 'consequence' of depression. Therefore, we here examined the effect of cognitive impairment induced by permanent occlusion of common carotid arteries, a model
Pascoe, Michaela C; Linden, Thomas
Elderly stroke survivors are at risk of malnutrition and long-term cognitive impairment. Vitamin B-related metabolites, folate and methylmalonic acid, have been implicated in cognitive function. We conducted a study exploring the relationship between blood folate, methylmalonic acid and post-stroke cognitive impairment. This is a cross sectional study of elderly Swedish patients (n=149) 20 months post-stroke, assessed using the Mini Mental State Examination, serum blood levels of methylmalonic acid and red blood cell levels of folate. Linear modeling indicated that low levels of blood folate and elevated methylmalonic acid significantly contributed to cognitive impairment in stroke survivors. Half of the stroke survivors were shown to have folate deficiency at 20 months after stroke. Folate deficiency is common long term after stroke and both low folate and elevated methylmalonic acid appear to be associated with long term cognitive impairment, in elderly Swedish stroke survivors.
Sonia Maria Dozzi Brucki
Full Text Available Prevalence studies of dementia and cognitive impairment in different cultures and environments are necessary. OBJECTIVE: To verify the prevalence of cognitive impairment and dementia in a rural homogeneous population from flooded areas in the Amazonian Basin. METHODS: A total of 163 subjects were interviewed with neurological, cognitive and functional evaluation. The individuals were classified as demented or cognitive impairment no dementia (CIND. RESULTS: cognitive impairment was observed in 11.4% (n=18 individuals. Ten out of the 18 were diagnosed as CIND and eight with dementia. The prevalence rate of dementia was 4.9% in subjects aged 50 years or over and of CIND was 6.1%. Considering only the elder group (>64 years of age, there was a 12.3% prevalence of dementia and 7.7% of CIND. CONCLUSION: In a homogeneous population, we observed a similar prevalence of dementia to rates reported by studies in Brazil and in other developed and developing countries.
Kurita, Geana Paula; Benthien, Kirstine Skov; Sjøgren, Per;
care. METHODS: Prospective longitudinal investigation derived from the European Palliative Care Cancer Symptom study (2011-2013) including patients with cancer in palliative care, ≥18 years, and with at least one assessment post-inclusion. For cognitive assessment, a 4-item version of the Mini Mental......) showed that those with low KPS (OR = 1.6, 95% CI 1.0-2.5) most often developed cognitive impairment, while patients with breast cancer (OR = 0.4, 95% CI 0.2-0.7) had lower odds for impairment. CONCLUSIONS: During palliative care, a substantial number of patients remained cognitively impaired or developed......PURPOSE: Studies with neuropsychological assessments in patients with cancer are sparse, and the evidence is very limited regarding their status of cognitive function over time. This study aimed at assessing the prevalence and predictors of cognitive impairment in patients with cancer in palliative...
Pacheco, Jennifer; Goh, Joshua O; Kraut, Michael A; Ferrucci, Luigi; Resnick, Susan M
Cross-sectional studies have shown regional differences in cortical thickness between healthy older adults and patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). We now demonstrate that participants who subsequently develop cognitive impairment leading to a diagnosis of MCI or AD (n = 25) experience greater cortical thinning in specific neuroanatomic regions compared with control participants who remained cognitively normal (n = 96). Based on 8 years of annual magnetic resonance imaging scans beginning an average of 11 years before onset of cognitive impairment, participants who developed cognitive impairment subsequent to the scanning period had greater longitudinal cortical thinning in the temporal poles and left medial temporal lobe compared with controls. No significant regional cortical thickness differences were found at baseline between the 2 study groups indicating that we are capturing a critical time when brain changes occur before behavioral manifestations of impairment are detectable. Our findings suggest that early events of the pathway that leads to cognitive impairment may involve the temporal lobe and that this increased atrophy could be considered an early biomarker of neurodegeneration predictive of cognitive impairment years later.
Pacheco, Jennifer; Goh, Joshua O.; Kraut, Michael A.; Ferrucci, Luigi; Resnick, Susan M.
Cross-sectional studies have shown regional differences in cortical thickness between healthy older adults and patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI). We now demonstrate that participants who subsequently develop cognitive impairment leading to a diagnosis of MCI or AD (n=25) experience greater cortical thinning in specific neuroanatomical regions compared to control participants who remained cognitively normal (n=96). Based on 8 years of annual MRI scans beginning an average of 11 years prior to onset of cognitive impairment, participants who developed cognitive impairment subsequent to the scanning period had greater longitudinal cortical thinning in the temporal poles and left medial temporal lobe compared to controls. No significant regional cortical thickness differences were found at baseline between the two study groups indicating that we are capturing a critical time when brain changes occur before behavioral manifestations of impairment are detectable. Our findings suggest that early events of the pathway that leads to cognitive impairment may involve the temporal lobe, and that this increased atrophy could be considered an early biomarker of neurodegeneration predictive of cognitive impairment years later. PMID:25311277
Fernández de Bobadilla, Ramón; Pagonabarraga, Javier; Martínez-Horta, Saül; Pascual-Sedano, Berta; Campolongo, Antonia; Kulisevsky, Jaime
Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and sensitivity to change in predementia stages of Parkinson's disease (PD) limit the utility of instruments measuring global cognition as screening and outcome measures in therapeutic trials. Investigators who were blinded to PD-Cognitive Rating Scale (PD-CRS) scores classified a cohort of prospectively recruited, nondemented patients into a PD with normal cognition (PD-NC) group and a PD with MCI (PD-MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia Rating Scale-2 (MDRS-2). The discriminative power of the PD-CRS for PD-MCI was examined in a representative sample of 234 patients (145 in the PD-NC group; 89 in the PD-MCI group) and in a control group of 98 healthy individuals. Sensitivity to change in the PD-CRS score (the minimal clinically important difference was examined with the Clinical Global Impression of Change scale and was calculated with a combination of distribution-based and anchor-based approaches) was explored in a 6-month observational multicenter trial involving a subset of 120 patients (PD-NC, 63; PD-MCI, 57). Regression analysis demonstrated that PD-CRS total scores (P < 0.001) and age (P = 0.01) independently differentiated PD-NC from PD-MCI. Area under the receiver operating characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80-0.90) indicated that a score ≤ 81 of 134 was the optimal cutoff point on the total score for the PD-CRS (sensitivity, 79%; specificity, 80%; positive predictive value, 59%; negative predictive value, 91%). A range of change from 10 to 13 points on the PD-CRS total score was indicative of clinically significant change. These findings suggest that the PD-CRS is a useful tool to identify PD-MCI and to track cognitive changes in nondemented patients with PD.
Whitson, Heather E.; Ansah, Deidra; Sanders, Linda L; Whitaker, Diane; Potter, Guy G.; Cousins, Scott W.; Steffens, David C.; Landerman, Lawrence R.; Pieper, Carl F.; Cohen, Harvey Jay
Background and Aims Comorbid cognitive impairment is common among visually impaired older adults. This study investigated whether baseline cognitive status predicts functional trajectories among older adults in low vision rehabilitation (LVR) for macular disease. Methods The Telephone Interview for Cognitive Status – modified (TICS-m) was administered to macular disease patients aged ≥ 65 years receiving outpatient LVR. Mixed models assessed the rate of change in instrumental activities of daily living and visual function measures over a mean follow-up of 115 days. Results Of 91 participants, 17 (18.7%) had cognitive impairment (TICS-m score ≤ 27) and 23 (25.3%) had marginal impairment (TICS-m scores 28 to 30). Controlling for age and gender, baseline cognitive status did not predict most functional outcomes. However, participants with marginal cognitive impairment experienced worse functional trajectories in ability to prepare meals (p=0.03).and activities that require distance vision (p = 0.05). Conclusion Patients with mild to moderate cognitive impairment should not be excluded from LVR, but programs should be prepared to detect and accommodate a range of cognitive ability. PMID:22526069
N. V. Pizova
Full Text Available The paper gives an update on the pathogenesis, clinical presentation, and pathomorphology of cognitive impairments (CIs in different autoimmune, endocrine, and infectious diseases: systemic lupus erythematosus, Sjögren’s syndrome, Behchet’s disease, primary angiitis of the central nervous system, polyarteritis nodosa, cryoglobulinemic vasculitis, hypothyroidism, herpetic lesion, and neurosyphilis. It is noted that treatment for CIs should be individual in terms of virulence factors. In vascular CIs, therapy should be aimed primarily at modifying risk factors and eliminating or reducing chronic brain ischemia. The prevention of progressive CI encompasses antihypertensive and antithrombotic therapies and surgical correction of atherosclerotic great artery stenosis. Control of hyperlipidemia, hyperglycemia and treatment of other somatic diseases are also of great importance. Such patients are usually given cetylcholinesterase inhibitors, acetylcholine precursors, antiglutamatergic agents, and metabolic and vascular drugs. By taking into account brain ischemia/ hypoxia in the above diseases, it is shown to be advisable to use antioxidants, cerebral active agents in particular, which have a complex neurometabolic effect.
David C Hess
Full Text Available There is a strong link between hypoperfusion and white matter (WM damage in patients with leukoaraiosis and vascular cognitive impairment (VCI. Other than management of vascular risk factors, there is no treatment for WM damage and VCI that delays progression of the disease process to dementia. Observational studies suggest that exercise may prevent or slow down the progression of Alzheimer′s disease (AD and VCI. However, getting patients to exercise is challenging, especially with advancing age and disability. Remote ischemic conditioning, an "exercise equivalent," allows exercise to be given with a "device" at home for long periods of time. Since remote ischemic conditioning (RIC increases cerebral blood flow (CBF in preclinical studies and in humans, RIC may be an ideal therapy to treat VCI and WM disease and perhaps even sporadic AD. By using magnetic resonance imaging (MRI imaging of WM progression, a sample size in the range of about 100 subjects per group could determine if RIC has activity in WM disease and VCI.
Koenig, O; Thomas-Antérion, C; Laurent, B
Two experiments were carried out to study procedural learning in Parkinson's disease (PD) patients. In Experiment 1, ten patients and their normal controls participated in a classical mirror reading task and in an inverted reading task where word-stimuli made of non inverted letters had to be processed from right to left (e.g., ygoloruen). In both tasks, reading times for new stimuli were compared to reading times for stimuli that repeated over blocks. Although PD patients and their controls exhibited learning for repeated words in both tasks, PD patients did not respond faster with practice for new words in the inverted reading task. In Experiment 2, PD patients and their controls were presented with an original dot counting task in which participants were asked to process a horizontal series of black and white dots from right to left and to indicate whether a dot that had been designated by a number at the beginning of each trial was black or white. Results showed that PD patients, in contrast to controls, did not exhibit learning in this task. Results are discussed in terms of the cognitive components involved in these tasks. It is suggested that PD patients are impaired in the acquisition of a right-to-left visual scanning skill that could be studied directly in Experiment 2.
Javier M Buldú
Full Text Available Whether the balance between integration and segregation of information in the brain is damaged in Mild Cognitive Impairment (MCI subjects is still a matter of debate. Here we characterize the functional network architecture of MCI subjects by means of complex networks analysis. Magnetoencephalograms (MEG time series obtained during a memory task were evaluated by synchronization likelihood (SL, to quantify the statistical dependence between MEG signals and to obtain the functional networks. Graphs from MCI subjects show an enhancement of the strength of connections, together with an increase in the outreach parameter, suggesting that memory processing in MCI subjects is associated with higher energy expenditure and a tendency toward random structure, which breaks the balance between integration and segregation. All features are reproduced by an evolutionary network model that simulates the degenerative process of a healthy functional network to that associated with MCI. Due to the high rate of conversion from MCI to Alzheimer Disease (AD, these results show that the analysis of functional networks could be an appropriate tool for the early detection of both MCI and AD.
Gupta, Sunita; Parrino, Taryn E.; Knight, Alecia G.; Ebenezer, Philip J.; Weidner, Adam M.; LeVine, Harry; Keller, Jeffrey N.; Markesbery, William R.
Abstract This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47phox and the catalytic subunit gp91phox was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91phox, moderate levels of gp91phox also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD. Antioxid. Redox Signal. 12, 1371–1382. PMID:19929442
Bialystok, Ellen; Craik, Fergus I. M.; Murphy, Kelly J.; Troyer, Angela K.
Objectives. Previous reports have found that lifelong bilingualism is associated with a delay in the onset of dementia, including Dementia of the Alzheimer’s Type (DAT). Because amnestic mild cognitive impairment (aMCI) is often a transition stage between normal aging and DAT, our aim in this paper was to establish whether this delay in symptom onset for bilinguals would also be seen in the onset of symptoms of aMCI and whether this delay would be consistent in different subtypes of aMCI. Method. We examined the effect of bilingualism on the age of diagnosis in individuals with single- or multiple-domain aMCI who were administered a battery of neuropsychological tests and questionnaires about their language and social background. Results. Our results showed an interaction between aMCI type and language history. Only individuals diagnosed with single-domain aMCI demonstrated a later age of diagnosis for bilinguals (M = 79.4 years) than monolinguals (M = 74.9 years). Discussion. This preliminary evidence suggests that the early protective advantage of bilingualism may be specific to single-domain aMCI, which is the type of aMCI most specifically associated with progression to DAT. PMID:22454387
Hu, Dong-Mei; Cheng, Xiao-Rui; Zhou, Wen-Xia; Zhang, Yong-Xiang; Zhou, Li-Chun
Repetitive transcranial of magnetic stimulation (rTMS), as a new electrophysiological technique, has been used in treating neurological and psychiatric diseases in clinical. In recent years, rTMS has also been employed to explore the treatment options for post stroke cognitive impairment (PSCI). Studies showed that rTMS was beneficial to recovery of post-stroke aphasia, improvement of memory dysfunction and alleviation of hemispatial neglect. Moreover, it is safe for patient within the recommended parameters of safety guidance. rTMS exerts therapeutic effects by interfering with the reconstruction of cortical network, improving the cerebral blood flow and metabolism, adjusting the ion balance by modulating cortical excitability. In addition, rTMS could enhance synaptic plasticity, inhibit the apoptosis, and regulate the transmission of a variety of neurotransmitters. It was reviewed that the basic principles of rTMS, the efficacy, safety and mechanism of rTMS in the treatment of PSCI, as well as the current problems and prospects in this paper.
Full Text Available Deficiency of protein phosphatase-2A is a key event in Alzheimer's disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer's disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer's disease patients.
Nir, Talia M; Jahanshad, Neda; Toga, Arthur W; Bernstein, Matt A; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M
Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 ± 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global "small-world" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian "expansion factor maps" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.
Tyrovolas, Stefanos; Koyanagi, Ai; Lara, Elvira
INTRODUCTION: The role of mild cognitive impairment (MCI) on falls among older adults remains under-investigated. The aim of this study was to evaluate the association between MCI and number of falls or occurrence of non-accidental falls among older adults. METHODS: Data from the first wave......; and no limitations in activities of daily living (ADL). Multivariable Poisson and logistic regression analyses were conducted to assess the association between MCI and number of falls or the presence of non-accidental falls in the past 12 months. RESULTS: The prevalence of MCI was 10.1%. In the fully-adjusted model......, MCI was associated with a higher rate of falls (PR=1.41 95%CI=1.05-1.89) and odds for non-accidental falls in the past 12 months (OR=1.67 95%CI=1.07-2.61). Muscle strength and performance indicators, and medical health conditions were influential factors in the association between MCI and falls...
Full Text Available In the present study, we examined the effect of schisandrin (SCH of Schisandra chinensis on the amyloid-beta1–42- (Aβ1–42- induced memory impairment in mice and elucidated the possible antioxidative mechanism. Mice were intracerebroventricular (i.c.v. injected with the aggregated Aβ1–42 and then treated with SCH (4, 12, and 36 mg/kg body weight or donepezil (DPZ, a reference drug (0.65 mg/kg by intragastric infusion for 14 days. Noncognitive disturbances and cognitive performance were evaluated by locomotor activity test, Y-maze test, and water maze test. Antioxidative enzyme activities including superoxide dismutase (SOD and glutathione peroxidase (GSH-px and levels of malondialdehyde (MDA, glutathione (GSH, and oxidized glutathione (GSSG within the cerebral cortex and hippocampus of mice were measured to elucidate the mechanism. Our results showed that SCH significantly improved Aβ1–42-induced short-term and spatial reference memory impairments in Y-maze test and water maze test. Furthermore, in the cerebral cortex and hippocampus of mice, SOD and GSH-px activities, GSH level, and GSH/GSSG ratio were increased, and levels of MDA and GSSG were decreased by the treatment of SCH. These results suggest that SCH is a potential cognitive enhancer against Alzheimer’s disease through antioxidative action.
Hu, Di; Cao, Yunfeng; He, Rongrong; Han, Na; Liu, Zhihui; Miao, Lijing; Yin, Jun
In the present study, we examined the effect of schisandrin (SCH) of Schisandra chinensis on the amyloid-beta(1-42)- (Aβ(1-42)-) induced memory impairment in mice and elucidated the possible antioxidative mechanism. Mice were intracerebroventricular (i.c.v.) injected with the aggregated Aβ(1-42) and then treated with SCH (4, 12, and 36 mg/kg body weight) or donepezil (DPZ), a reference drug (0.65 mg/kg) by intragastric infusion for 14 days. Noncognitive disturbances and cognitive performance were evaluated by locomotor activity test, Y-maze test, and water maze test. Antioxidative enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and levels of malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG) within the cerebral cortex and hippocampus of mice were measured to elucidate the mechanism. Our results showed that SCH significantly improved Aβ(1-42)-induced short-term and spatial reference memory impairments in Y-maze test and water maze test. Furthermore, in the cerebral cortex and hippocampus of mice, SOD and GSH-px activities, GSH level, and GSH/GSSG ratio were increased, and levels of MDA and GSSG were decreased by the treatment of SCH. These results suggest that SCH is a potential cognitive enhancer against Alzheimer's disease through antioxidative action.
Ruchel, Jader B; Braun, Josiane B S; Adefegha, Stephen A; Guedes Manzoni, Alessandra; Abdalla, Fátima H; de Oliveira, Juliana S; Trelles, Kelly; Signor, Cristiane; Lopes, Sônia T A; da Silva, Cássia B; Castilhos, Lívia G; Rubin, Maribel A; Leal, Daniela B R
Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.
Wu, Ting; Sun, Jianning; Kagota, Satomi; Maruyama, Kana; Wakuda, Hirokazu; Shinozuka, Kazumasa
Panax notoginseng saponins (PNS) are major components of Panax notoginseng, a herb with established clinical efficacy against vascular diseases. SHRSP.Z-Lepr(fa) /IzmDmcr (SHRSP.ZF) rats, a new animal model for metabolic syndrome, display an impaired vasorelaxation response in aortas and mesenteric arteries that is mediated by nitric oxide (NO). This study investigated whether PNS and its components can ameliorate this vascular dysfunction in SHRSP.ZF rats. In an in vitro study, in the presence or absence of PNS and its components, vasodilation in response to nitroprusside was determined from myographs under isometric tension conditions in aortas and mesenteric arteries from male SHRSP.ZF rats at 18-20 weeks of age. In an in vivo study, PNS (30 mg/kg per day) was orally administered to SHRSP.ZF rats from 8 to 20 weeks of age. In vitro treatment with PNS and Ginsenoside Rb1 increased nitroprusside-induced relaxation of aortas and mesenteric arteries in SHRSP.ZF rats. The PNS-induced increase was not affected by a nitric oxide (NO) synthase inhibitor or endothelium denudation. Relaxation in response to a cell-permeable cGMP analogue was increased by PNS, but cGMP accumulation by nitroprusside was not altered. In vivo treatment with PNS in SHRSP.ZF rats lowered blood pressure and increased relaxation and the expression of soluble guanylyl cyclase protein in arteries, without affecting metabolic abnormalities. These results indicate that PNS causes an increase in vasodilation in response to NO and a decrease in blood pressure, resulting in protection against vascular dysfunction in SHRSP.ZF rats. PNS might be beneficial in alleviating impaired vasodilation in metabolic syndrome.
SHIN Suk-Chul; LEE Dong-Ung
AIM:To study the chemical constituents and their anti-amnesic effect from the hooks of Uncaria rhynchophylla.METHODS:The isolation of compounds was performed by chromatographic techniques and their structures were identified on the basis of spectral analysis.Their ameliorating effects on scopolamine-induced memory impairment in vivo using a Morris water-maze task and passive avoidance task system were evaluated.RESULTS:Activity-guided fractionation of the total extracts resulted in the isolation of four constituents,trans-anethole (1),p-anisaldehyde (2),estragole (3),and 3-oxo-olean-12-en-28-oic acid (4),which were found for the first time from this plant.CONCLUSION:Compound 1 exhibited a better memory enhancing effect than tacrine,a positive agent,at the same dose in the passive avoidance test and a similar property in the water-maze test,and its action may be mediated,in part,by the acetylcholine enhancing cholinergic nervous system.
Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne
Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus, spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (rs=0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (rs=0.56) and hippocampus (rs=−0.62) or septum (rs=−0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes. PMID:28039490
Yates, Jennifer A; Clare, Linda; Woods, Robert T; Matthews, Fiona E
Subjective memory complaints (SMC) are a criterion in many definitions of mild cognitive impairment (MCI). However, there is controversy over whether this is useful and appropriate, as previous research has suggested that SMC may be a function of mood problems such as anxiety and depression. This paper aimed to establish the relationship between MCI and mood in older people and to investigate the role that SMC play in the relationship. Structured interviews were conducted with community dwelling older people in Wales to collect information regarding cognitive functioning, mood, and well-being. A widely-used algorithm was used to categorize 3,173 participants into three groups: not cognitively impaired, MCI including SMC (MCI), and MCI without SMC (MCIW). The odds of experiencing anxiety or depression were calculated for each cognitive group. Participants with MCI had increased odds of experiencing symptoms of both anxiety and depression, but the odds were not changed for participants in the not cognitively impaired or MCIW categories. A mediation analysis was performed on the whole sample using cognition as a dichotomous variable, grouped using an age-, education-, and gender-adjusted median cut off point. This showed that SMC partially mediated the relationship between anxiety and cognition, and depression and cognition. Mood problems may be related to SMC rather than objective cognitive impairment, as only participants with MCI that included SMC showed increased odds of experiencing anxiety and depression. SMC are likely to play a mediating role in the relationship between mood and cognitive functioning.
Irina Sergeyevna Preobrazhenskaya
Full Text Available The review of literature considers the possible mechanisms responsible for the development of sleep disorders in patients with varying degrees of cognitive impairments. It assesses the association of the severity of cognitive impairments (CI with the degree of sleep disorders. The treatment of sleep disorders in patients with cognitive disorders, the benefits and risks of current hypnotic drugs are discussed in detail. Recommendations are given to manage patients with sleep disorders concurrent with cognitive dysfunctions. Melatonin preparations are noted to be effective in treating insomnia in patients with CI.
Morley, John E.; Morris, John C.; Berg-Weger, Marla; Borson, Soo; Carpenter, Brian D.; del Campo, Natalia; Dubois, Bruno; Fargo, Keith; Fitten, L. Jaime; Flaherty, Joseph H.; Ganguli, Mary; Grossberg, George T.; Malmstrom, Theodore K.; Petersen, Ronald D.; Rodriguez, Carroll; Saykin, Andrew J.; Scheltens, Philip; Tangalos, Eric G.; Verghese, Joe; Wilcock, Gordon; Winblad, Bengt; Woo, Jean; Vellas, Bruno
Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States’ Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient’s right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline. PMID:26315321
Kumar, Hariom; Sharma, Bhupesh
Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.
Al-Amin, Md Mamun; Reza, Hasan Mahmud; Saadi, Hasan Mahmud; Mahmud, Waich; Ibrahim, Abdirahman Adam; Alam, Musrura Mefta; Kabir, Nadia; Saifullah, A R M; Tropa, Sarjana Tarannum; Quddus, A H M Ruhul
Aluminum chloride induces neurodegenerative disease in animal model. Evidence suggests that aluminum intake results in the activation of glial cells and generation of reactive oxygen species. By contrast, astaxanthin is an antioxidant having potential neuroprotective activity. In this study, we investigate the effect of astaxanthin on aluminum chloride-exposed behavioral brain function and neuronal oxidative stress (OS). Male Swiss albino mice (4 months old) were divided into 4 groups: (i) control (distilled water), (ii) aluminum chloride, (iii) astaxanthin+aluminum chloride, and (iv) astaxanthin. Two behavioral tests; radial arm maze and open field test were conducted, and OS markers were assayed from the brain and liver tissues following 42 days of treatment. Aluminum exposed group showed a significant reduction in spatial memory performance and anxiety-like behavior. Moreover, aluminum group exhibited a marked deterioration of oxidative markers; lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH) and advanced oxidation of protein products (AOPP) in the brain. To the contrary, co-administration of astaxanthin and aluminum has shown improved spatial memory, locomotor activity, and OS. These results indicate that astaxanthin improves aluminum-induced impaired memory performances presumably by the reduction of OS in the distinct brain regions. We suggest a future study to determine the underlying mechanism of astaxanthin in improving aluminum-exposed behavioral deficits.
Toshihito Shibata; Toru Mizuguchi; Yukio Nakamura; Masaki Kawamoto; Makoto Meguro; Shigenori Ota; Koichi Hirata; Hidekazu Ooe; Toshihiro Mitaka
AIM:To determine if liver regeneration (LR) could be disturbed following radiofrequency (RF) ablation and whether modification of LR by steroid administration occurs.METHOIDS:Sham operation,partial hepatectomy (PH),and partial hepatectomy with radiofrequency ablation (PHA) were performed on adult Fisher 344 rats.We investigated the recovery of liver volume,DNA synthetic activities,serum cytokine/chemokine levels and signal transducers and activators of transcription 3 DNA-binding activities in the nucleus after the operations.Additionally,the effects of steroid (dexamethasone) pretreatment in the PH group (S-PH) and the PHA group (S-PHA) were compared.RESULTS:The LR after PHA was impaired,with high serum cytokine/chemokine induction compared to PH,although the ratio of the residual liver weight to body weight was not significantly different.Steroid pretreatment disturbed LR in the S-PH group.On the other hand,low-dose steroid pretreatment improved LR and suppressed tumor necrosis factor (TNF)-α elevation in the S-PHA group,with recovery of STAT3 DNA-binding activity.On the other hand,low-dose steroid pretreatment improved LR and suppressed TNF-α elevation in the S-PHA group,with recovery of STAT3 DNA-binding activity.CONCLUSION:LR is disturbed after RF ablation,with high serum cytokine/chemokine induction.Low-dose steroid administration can improve LR after RF ablation with TNF-α suppression.
Full Text Available Neeta Thakur1, Paul D Blanc2, Laura J Julian1, Edward H Yelin3, Patricia P Katz3, Stephen Sidney4, Carlos Iribarren4, Mark D Eisner1,21Department of Medicine, 2Division of Occupational and Environmental Medicine and Division of Pulmonary and Critical Care Medicine, 3Institute for Health Policy Studies, Department of Medicine, University of California, San Francisco, CA, USA, 4Division of Research, Kaiser Permanente, Oakland, CA, USABackground: Several studies have shown an association between chronic obstructive pulmonary disease (COPD and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy.Methods: We used the Function, Living, Outcomes and Work (FLOW cohort study of adults with COPD (n = 1202 and referent subjects matched by age, sex, and race (n = 302 to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV1; the validated COPD Severity Score; and the BMI (Body Mass Index, Obstruction, Dyspnea, Exercise Capacity (BODE Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking.Results: COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043–6.64. Among COPD patients, none of the COPD severity measures were associated with the
Full Text Available BACKGROUND: Cognitive impairment is associated with a negative prognosis in amyotrophic lateral sclerosis (ALS, as well as with clinical specificity. We investigate neuropsychological function in ALS patients without known genetic mutations in a Korean tertiary clinic. METHODS: Three hundred and eighteen patients were enrolled in a prospective longitudinal cohort from September 2008 to February 2012. At the time of diagnosis of sporadic ALS, we carried out genetic and comprehensive neuropsychological tests on all patients, and collected demographic and clinical characteristics. Six cognitive domains, namely executive function, attention, language, calculation, visuospatial function and memory were evaluated. ANOVA and t-tests were used to assess differences in clinical characteristics and neuropsychological parameters between sporadic ALS patients. The Kaplan-Meier method and Cox proportional hazard model were used for survival analysis. RESULTS: One hundred and sixty-six patients were categorized into five subtypes: normal cognition (ALS pure, cognitive impairment (ALSci, behavioral impairment (ALSbi, frontotemporal dementia (ALS-FTD, and other types of dementia. Seventy patients (70/166, 42.2% were cognitively or behaviorally impaired. Among the impaired patients, eight (8/166, 4.8% had FTD-type dementia and one (1/166, 0.6% was Alzheimer's disease-type. The ALS patients with cognitive impairment (ALSci and with FTD (ALS-FTD were more severely impaired in executive function, attention, language and memory than the cognitively intact ALS patients (ALS pure. In a survival analysis, ALSci (β = 1.925, p = 0.025 and ALS-FTD groups (β = 4.150, p = 0.019 tended to have shorter survival than the ALS pure group. CONCLUSIONS: About half of ALS patients without known genetic variation have cognitive or behavioral impairment. ALS patients with cognitive abnormalities, especially FTD, have a poorer prognosis than those without cognitive impairment. In
Bora, Emre; Yücel, Murat; Pantelis, Christos
It has recently been suggested that the diagnostic criteria of schizophrenia should include specific reference to cognitive impairments characterizing the disorder. Arguments in support of this assertion contend that such inclusion would not only serve to increase the awareness of cognitive deficits in affected patients, among both clinicians and researchers alike, but also increase the "point of rarity" between schizophrenia and mood disorders. The aim of the current article is to examine this latter assertion in light of the recent opinion piece provided by Keefe and Fenton (Keefe RSE, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull. 2007;33:912-920). Through literature review, we explore the issue of whether cognitive deficits do in fact differentiate the major psychoses. The overall results of this inquiry suggest that inclusion of cognitive impairment criteria in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-V) would not provide a major advancement in discriminating schizophrenia from bipolar disorder and affective psychoses. Therefore, while cognitive impairment should be included in DSM-V, it should not dictate diagnostic specificity--at least not until more comprehensive evidence-based reviews of the current diagnostic system have been undertaken. Based on this evidence, we consider several alternatives for the DSM-V definition of cognitive impairment in schizophrenia, including (1) the inclusion of cognitive impairment as a specifier and (2) the definition of cognitive impairment as a dimension within a hybrid categorical-dimensional system. Given the state of current evidence, these possibilities appear to represent the most parsimonious approaches to the inclusion of cognitive deficits in the diagnostic criteria of schizophrenia and, potentially, of mood disorders.
Full Text Available Identification and modification of the risk factors for cognitive decline throughout the adult life span are priority subjects in a progressively aging society; however, much remains to be learned. The aim of this study was to understand whether changes in cognitive function can be affected by hearing impairment (HI and whether the impact of HI differs depending on the cognitive domain. A total of 1,109 individuals aged 60 – 79 years at baseline who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences (NILS-LSA was followed up for a maximum of 13.3 years. Cognitive function was evaluated using four subtests of the Japanese Wechsler Adult Intelligence Scale-Revised Short Forms: namely, Information, Similarities, Picture Completion, and the Digit Symbol Substitution subtests. The HI was defined as a pure-tone average of the better ear greater than 25 dB. A longitudinal analysis was performed of 4,437 observations obtained during a follow-up period of approximately 12 years. We estimated linear changes in subtest scores by HI status, using the time-varying mixed-effects regression model, which included fixed terms for the intercept, HI status at baseline, time (years elapsed since baseline, and an HI × time interaction term adjusted for age at baseline, sex, education, and other possible confounders. There were significant main effects of HI on the scores of the four subtests after adjustment. The HI × time interaction was significant for the scores of the Information (p = 0.001 and Digit Symbol Substitution subtests (p = 0.001. The scores of the HI group declined faster in the Information and Digit Symbol Substitution subtests compared to those of the no-HI group. The model-predicted 12-year slope using a mean baseline age (68.7 years indicated no significant decline in the individuals without HI at baseline for the Information and Similarities subtests, however, this tolerance was lost in the
Burrows, Emma L; McOmish, Caitlin E; Buret, Laetitia S; Van den Buuse, Maarten; Hannan, Anthony J
Schizophrenia arises from a complex interplay between genetic and environmental factors. Abnormalities in glutamatergic signaling have been proposed to underlie the emergence of symptoms, in light of various lines of evidence, including the psychotomimetic effects of NMDA receptor antagonists. Metabotropic glutamate receptor 5 (mGlu5) has also been implicated in the disorder, and has been shown to physically interact with NMDA receptors. To clarify the role of mGlu5-dependent behavioral expression by environmental factors, we assessed mGlu5 knockout (KO) mice after exposure to environmental enrichment (EE) or reared under standard conditions. The mGlu5 KO mice showed reduced prepulse inhibition (PPI), long-term memory deficits, and spontaneous locomotor hyperactivity, which were all attenuated by EE. Examining the cellular impact of genetic and environmental manipulation, we show that EE significantly increased pyramidal cell dendritic branching and BDNF protein levels in the hippocampus of wild-type mice; however, mGlu5 KO mice were resistant to these alterations, suggesting that mGlu5 is critical to these responses. A selective effect of EE on the behavioral response to the NMDA receptor antagonist MK-801 in mGlu5 KO mice was seen. MK-801-induced hyperlocomotion was further potentiated in enriched mGlu5 KO mice and treatment with MK-801 reinstated PPI disruption in EE mGlu5 KO mice only, a response that is absent under standard housing conditions. Together, these results demonstrate an important role for mGlu5 in environmental modulation of schizophrenia-related behavioral impairments. Furthermore, this role of the mGlu5 receptor is mediated by interaction with NMDA receptor function, which may inform development of novel therapeutics.
Mahantshetti Niranjana S
Full Text Available Abstract Background This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia. Methods/Design This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors. Discussion The trial is supervised by a trial steering committee, and an independent data monitoring
Arias Tapia, Susana A.; Martínez-Tomás, Rafael; Gómez, Héctor F.; Hernández del Salto, Víctor; Sánchez Guerrero, Javier; Mocha-Bonilla, J. A.; Barbosa Corbacho, José; Khan, Azizudin; Chicaiza Redin, Veronica
The present study aims to identify early cognitive impairment through the efficient use of therapies that can improve the quality of daily life and prevent disease progress. We propose a methodology based on the hypothesis that the dissociation between oral semantic expression and the physical expressions, facial gestures, or emotions transmitted in a person's tone of voice is a possible indicator of cognitive impairment. Experiments were carried out with phrases, analyzing the semantics of the message, and the tone of the voice of patients through unstructured interviews in healthy people and patients at an early Alzheimer's stage. The results show that the dissociation in cognitive impairment was an effective indicator, arising from patterns of inconsistency between the analyzed elements. Although the results of our study are encouraging, we believe that further studies are necessary to confirm that this dissociation is a probable indicator of cognitive impairment. PMID:27683555
Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.
Almeida, Sérgio Monteiro de
Cognitive impairment and major depressive disorder (MDD) are common HIV-1 central nervous system (CNS) complications. Their frequencies in AIDS patients are 36% and 45%, respectively. The diagnoses of HIV cognitive impairment are made by clinical criteria, no single laboratory test or biomarker establishes the diagnosis. Factors of indirect neuronal injury related with the pathophysiology of the HIV infection in the CNS, are the factors studied as biomarkers. In the present no biomarker is established to the diagnosis of HIV cognitive impairment, much still needs to be done. We review in this paper some biomarkers in cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive impairment. Diagnosing depression in the context of HIV can be challenging, to identify a biomarker that could help in the diagnosis would be very important, although MDD risks and neurobiology are still poorly understood.
Sergio Monteiro de Almeida
Full Text Available Cognitive impairment and major depressive disorder (MDD are common HIV-1 central nervous system (CNS complications. Their frequencies in AIDS patients are 36% and 45%, respectively. The diagnoses of HIV cognitive impairment are made by clinical criteria, no single laboratory test or biomarker establishes the diagnosis. Factors of indirect neuronal injury related with the pathophysiology of the HIV infection in the CNS, are the factors studied as biomarkers. In the present no biomarker is established to the diagnosis of HIV cognitive impairment, much still needs to be done. We review in this paper some biomarkers in cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive impairment. Diagnosing depression in the context of HIV can be challenging, to identify a biomarker that could help in the diagnosis would be very important, although MDD risks and neurobiology are still poorly understood.
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
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.
Schultz-Larsen, Kirsten; Rahmanfard, Naghmeh; Kreiner, Svend;
by sociodemographic and health variables including cognitive functioning. Only in women, stroke and diabetes remained statistically significant associated with mortality. CONCLUSION: The association between cognitive impairment and mortality reflects processes different from those underlying a simple relation between......OBJECTIVE: This study explores the association between cognitive impairment and mortality in late senescence. A specific purpose was to validate the ability of a short form of the Mini-Mental State Examination (MMSE) in predicting mortality. STUDY DESIGN AND SETTING: The cognition-mortality link......, as assessed by the original MMSE and D-MMSE (a subscale associated to dementia) was estimated on a community sample of 1,111 older people using Cox proportional hazards models. RESULTS: Impaired cognitive function as assessed by both the original MMSE and D-MMSE predicted mortality in older men and women over...
Akl, Ahmad; Snoek, Jasper; Mihailidis, Alex
With a globally aging population, the burden of care of cognitively impaired older adults is becoming increasingly concerning. Instances of Alzheimer's disease and other forms of dementia are becoming ever more frequent. Earlier detection of cognitive impairment offers significant benefits, but remains difficult to do in practice. In this paper, we develop statistical models of the behavior of older adults within their homes using sensor data in order to detect the early onset of cognitive decline. Specifically, we use inhomogenous Poisson processes to model the presence of subjects within different rooms throughout the day in the home using unobtrusive sensing technologies. We compare the distributions learned from cognitively intact and impaired subjects using information theoretic tools and observe statistical differences between the two populations which we believe can be used to help detect the onset of cognitive decline.
Alex eBertrams; Baumeister, Roy F.; Chris eEnglert
We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examination...
Bertrams, Alex; Baumeister, Roy F.; Englert, Chris
We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examination...
Li, Chung-Yi; Wu, Shwu Chong; Sung, Fung-Chang
We used a nested case-control design with study participants sampled from two cohorts, for a total of 2,198 elderly people 65 years or older and completed cognitive tests between 1993 and 1997, to assess the association between an individual's lifetime principal occupation and the subsequent risk of cognitive impairment. Cases consisted of 290 older adults with impaired cognitive functioning. For each case, two controls with comparable age (within 5 years) and sex frequencies were randomly sampled from the seniors free of cognitive impairment. Occupational data were collected through interviews. Individual's job content was coded into one of the occupational categories or the occupation-based social classes. Compared to those who were former legislators, government administrators, or business executives and managers, a significantly elevated risk of cognitive impairment was estimated for those who were employed as agriculture/animal husbandry/forestry/fishing workers (odds ratio (OR)=3.2), craft and related trades workers (OR=2.2), plant and machine operators and assemblers (OR=14.7), workers of elementary occupations (OR=3.2), or housekeepers (OR=2.6). We also observed health inequalities in the risk of cognitive impairment across social classes with a significant dose-response trend in which unskilled blue-collar workers had the highest risk. After adjustment for education, we still observed an inverse relationship between risk of cognitive impairment and occupational class. This may mean that lifetime longest-held occupation is more intimately involved in the causal pathways leading to cognitive impairment. Further studies that collect information on specific work hazards would help make specific interpretations of the observed effect of lifetime longest-held occupation in early adulthood on risk of cognitive decline in late life.
D. V. Moretti
Full Text Available We evaluated the relationship between brain rhythmicity and both the cerebrovascular damage (CVD and amygdalohippocampal complex (AHC atrophy, as revealed by scalp electroencephalography (EEG in a cohort of subjects with mild cognitive impairment (MCI. All MCI subjects underwent EEG recording and magnetic resonance imaging. EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands. In the spectral band power the severity of CVD was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. On the other side, the group with moderate hippocampal atrophy showed the highest increase of alpha2 and alpha3 power. Moreover, when the amygdalar and hippocampal volumes are separately considered, within amygdalohippocampal complex (AHC, the increase of theta/gamma ratio is best associated with amygdalar atrophy whereas alpha3/alpha2 ratio is best associated with hippocampal atrophy. CVD and AHC damages are associated with specific EEG markers. So far, these EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI.
Full Text Available Aging and mild cognitive impairment are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer’s disease, which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. Mild cognitive impairment is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5-15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of mild cognitive impairment to Alzheimer’s disease might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat Alzheimer’s disease, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and mild cognitive impairment populations. Previous studies have found some cognitive brain networks disrupted in aging and mild cognitive impairment population, and physical exercise could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective physical exercise programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and mild cognitive impairment to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions.
Maju Mathew Koola
Full Text Available The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS project designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia, identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α7 nicotinic receptors. Memantine is an N-methyl-D-aspartate (NMDA receptor antagonist. There is evidence to suggest that the combination of galantamine and memantine may be effective in the treatment of cognitive impairments in schizophrenia. There is a growing body of evidence that excess kynurenic acid (KYNA is associated with cognitive impairments in schizophrenia. The α-7 nicotinic and the NMDA receptors may counteract the effects of kynurenic acid (KYNA resulting in cognitive enhancement. Galantamine and memantine through its α-7 nicotinic and NMDA receptors respectively may counteract the effects of KYNA thereby improving cognitive impairments. The Single Nucleotide Polymorphisms in the Cholinergic Receptor, Nicotinic, Alpha 7 gene (CHRNA7, Glutamate (NMDA Receptor, Metabotropic 1 (GRM1 gene, Dystrobrevin Binding Protein 1 (DTNBP1 and kynurenine 3-monooxygenase (KMO gene may predict treatment response to galantamine and memantine combination for cognitive impairments in schizophrenia in the kynurenine pathway.
Borghgraef, Cindy; Libert, Yves; Etienne, Anne-Marie; Delvaux, Nicole; Reynaert, Christine; Razavi, Darius
Various studies highlight cognitive impairments in cancer patients. This paper proposes a review of longitudinal controlled studies evaluating the efficacy of interventions aiming to reduce these cognitive impairments. Longitudinal controlled studies evaluating the efficacy of interventions aiming to reduce cognitive impairments in adult cancer patients and published between 1993 and 2013 were identified, with the exception of studies that implied patients suffering from CNS tumor or metastasis. Pharmacological interventions (n = 11) suggested the positive impact of modafinil on memory and executive functions. Non-pharmacological interventions (n = 10) suggested the positive impact of cognitive revalidation and stimulation programs, psycho-education and meditation on several memory, attentional and executive objective as well as subjective functions. Non-pharmacological interventions show more significant cognitive benefits than pharmacological interventions. Some longitudinal controlled studies support the usefulness of interventions aiming to reduce cognitive impairments in cancer patients. Further studies should evaluate the effectiveness of programs combining technics aiming to reduce cognitive impairments and psychotherapeutic technics aiming to support patients' coping with illness.
Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes
While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD.
Evans, Matthew C.; Barnes, Josephine; Nielsen, Casper; Clegg, Shona L.; Blair, Melanie; Douiri, Abdel; Boyes, Richard G.; Fox, Nick C. [UCL Institute of Neurology, Dementia Research Centre, London (United Kingdom); Kim, Lois G. [UCL Institute of Neurology, Dementia Research Centre, London (United Kingdom); London School of Hygiene and Tropical Medicine, London (United Kingdom); Leung, Kelvin K.; Ourselin, Sebastien [UCL Institute of Neurology, Dementia Research Centre, London (United Kingdom); University College London, Centre for Medical Image Computing, London (United Kingdom)
To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects. In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period. Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects. Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers. (orig.)
Halder, Sumita; Kar, Rajarshi; Galav, Vikas; Mehta, Ashish K; Bhattacharya, Swapan K; Mediratta, Pramod K; Banerjee, Basu D
Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.
Goldman, Jennifer G; Holden, Samantha; Bernard, Bryan; Ouyang, Bichun; Goetz, Christopher G; Stebbins, Glenn T
The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI) represent a first step toward a uniform definition of PD-MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy-six non-demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD-MCI or PD with normal cognition (PD-NC). The concordance of PD-MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD-MCI or PD-NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD-MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD-MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD-MCI from PD-NC compared with other cutoff scores. With the MDS PD-MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD-MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD-MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD-MCI.
Preziosa, Paolo; Rocca, Maria A; Pagani, Elisabetta; Stromillo, Maria Laura; Enzinger, Christian; Gallo, Antonio; Hulst, Hanneke E; Atzori, Matteo; Pareto, Deborah; Riccitelli, Gianna C; Copetti, Massimiliano; De Stefano, Nicola; Fazekas, Franz; Bisecco, Alvino; Barkhof, Frederik; Yousry, Tarek A; Arévalo, Maria J; Filippi, Massimo
In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel-wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS.
Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Nuñez del Prado, Liza; Parodi, José; Guevara-Silva, Erik; Castro-Suarez, Sheila; Montesinos, Rosa; Cortijo, Patricia
Background/Aims Dementia is a worldwide public health problem and there are several diagnostic tools for its assessment. The aim of this study was to evaluate the performance of the Memory Alteration Test (M@T) to discriminate between patients with early Alzheimer's disease (AD), patients with amnestic mild cognitive impairment (a-MCI), and subjects with a cognitively healthy status (CHS). Methods The discriminative validity was assessed in a sample of 90 patients with AD, 45 patients with a-MCI, and 180 subjects with CHS. Clinical, functional, and cognitive studies were independently performed in a blinded fashion and the gold standard diagnosis was established by consensus on the basis of these results. The test performance was assessed by means of a receiver operating characteristic curve analysis as area under the curve (AUC). Results M@T mean scores were 17.7 (SD = 5.7) in AD, 30.8 (SD = 2.3) in a-MCI, and 44.5 (SD = 3.1) in CHS. A cutoff score of 37 points had a sensitivity of 98.3% and a specificity of 97.8% to differentiate a-MCI from CHS (AUC = 0.999). A cutoff score of 27 points had a sensitivity of 100% and a specificity of 98.9% to differentiate mild AD from a-MCI and from CHS (AUC = 1.000). Conclusions The M@T had a high performance in the discrimination between early AD, a-MCI and CHS. PMID:25298775
Eun Hyun Seo
Full Text Available The conceptual significance of understanding functional brain alterations and cognitive deficits associated with Alzheimer's disease (AD process has been widely established. However, the whole-brain functional networks of AD and its prodromal stage, mild cognitive impairment (MCI, are not well clarified yet. In this study, we compared the characteristics of the whole-brain functional networks among cognitively normal (CN, MCI, and AD individuals by applying graph theoretical analyses to [(18F] fluorodeoxyglucose positron emission tomography (FDG-PET data. Ninety-four CN elderly, 183 with MCI, and 216 with AD underwent clinical evaluation and FDG-PET scan. The overall small-world property as seen in the CN whole-brain network was preserved in MCI and AD. In contrast, individual parameters of the network were altered with the following patterns of changes: local clustering of networks was lower in both MCI and AD compared to CN, while path length was not different among the three groups. Then, MCI had a lower level of local clustering than AD. Subgroup analyses for AD also revealed that very mild AD had lower local clustering and shorter path length compared to mild AD. Regarding the local properties of the whole-brain networks, MCI and AD had significantly decreased normalized betweenness centrality in several hubs regionally associated with the default mode network compared to CN. Our results suggest that the functional integration in whole-brain network progressively declines due to the AD process. On the other hand, functional relatedness between neighboring brain regions may not gradually decrease, but be the most severely altered in MCI stage and gradually re-increase in clinical AD stages.
Full Text Available Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET and a mind-body practice (yogic meditation, in healthy seniors with mild cognitive impairment (MCI using structural magnetic resonance imaging (MRI and proton magnetic resonance spectroscopy (1H-MRS. Senior participants (age ≥ 55 years with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini yoga for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC and bilateral hippocampus were measured by structural MRI and 1H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamate-glutamine (Glx, choline-containing compounds (Cho, including glycerophosphocholine and phosphocholine, gamma-aminobutyric acid (GABA, and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG. In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. 1H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with mild cognitive impairment. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes.
Barone, F.C.; Gustafson, D.; Crystal, H.A.; Moreno, H.; Adamski, M.G.; Arai, K.; Baird, A.E.; Balucani, C.; Brickman, A.M.; Cechetto, D.; Gorelick, P.; Biessels, G.J.; Kiliaan, A.J.; Launer, L.; Schneider, J.; Sorond, F.A.; Whitmer, R.; Wright, C.; Zhang, Z.G.
As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementi
Park, Juyoung; Castellanos-Brown, Karen; Belcher, John
Objective: Pain assessment for nonverbal older adults with cognitive impairments or dementia presents many challenges, and it is important to determine which scales are most useful in assessing pain among this population. Method: In this review 11 observational scales for assessment of pain in older adults with dementia or cognitive impairments…
Pfeiffer, Helle Cecilie Viekilde; Løkkegaard, A; Zoetmulder, Marielle;
In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Parkinson's disease-mild cognitive impairment (PD-MCI) are common. PD-MCI is a risk factor for developing PDD. Knowledge of cognition in early-stages PD is essential in understanding and predicting the dementia process....
Zuidema, Sytse; Koopmans, Raymond; Verhey, Frans
The prevalence of neuropsychiatric symptoms and the influence of predictive factors in cognitively impaired nursing home patients were reviewed. Articles were identified by means of a MEDLINE and PsychInfo literature search. Neuropsychiatric symptoms were present in more than 80% of the cognitively
Tu, Faping; Li, Jingdong; Wang, Ji; Li, Qiang; Chu, Weihua
Previously, hepatic ischemia followed by reperfusion (hepatic I/R) has been found to cause cognitive impairment. Hydrogen sulfide (H2S) attenuates hepatectomy induced cognitive deficits and also protects against cognitive dysfunction induced by neurodegenerative diseases. In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H2S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatment with NaHS alleviated hepatic I/R induced these neuroinflammatory changes and effectively improved cognitive function. Thus, NaHS appears to protect against cognitive impairment in rats undergoing hepatic I/R by attenuating neuroinflammation in the hippocampus.
Scherder, EJA; Van Paasschen, J; Deijen, JB; Van der Knokke, S; Orlebeke, JFK; Burgers, [No Value; Devriese, PP; Swaab, DF; Sergeant, JA
The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. S
Scherder, E.J.A.; Paasschen, J. van; Deijen, J.-B.; Knokke, S. van der; Orlebeke, J.F.K.; Burgers, I.; DeVriesse, P.-P.; Swaab, D.F.; Sergeant, J.A.
The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. S
Benedictus, Marieke R.; Spikman, Jacoba M.; van der Naalt, Joukje
Benedictus MR, Spikman JM, van der Naalt J. Cognitive and behavioral impairment in traumatic brain injury related to outcome and return to work. Arch Phys Med Rehabil 2010;91:1436-41. Objective: To evaluate the cognitive and behavioral disturbances related to return to work (RTW) in patients with tr
Geurtsen, G.J.; Hoogland, J.; Goldman, J.G.; Schmand, B.A.; Tröster, A.I.; Burn, D.J.; Litvan, I.
Dementia in Parkinson's disease (PD) is a serious health issue and a major concern for many patients. In most cases mild cognitive impairment (MCI) is considered a transitional stage between normal cognitive functioning and dementia which is of potential importance in the early identification of pat
Zhu, Lingpeng; Chen, Tong; Chang, Xiayun; Zhou, Rui; Luo, Fen; Liu, Jingyan; Zhang, Kai; Wang, Yue; Yang, Ying; Long, Hongyan; Liu, Yu; Yan, Tianhua; Ma, Chunhua
The prevalence of cognitive impairment in rheumatoid arthritis (RA) patients was increasingly serious nowadays. The purpose of the current study was to explore whether salidroside (Sal) could alleviate arthritis-induced cognition deficits and examine the relationship between the impairment and Rho/ROCK/NF-κB pathway. Collagen-induced arthritis (CIA) was established by the injection of chicken type II collagen (CII), complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Arthritic lesions of CIA rats were assessed by arthritis index score, swelling of paws and histological analysis. Cognitive deficits symptoms of CIA rats were monitored through Morris water maze test. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and serum were significantly reduced with salidroside (20 mg/kg, 40 mg/kg) treatment compared with those in the CIA group. In parallel, we demonstrated that the expressions of RhoA, ROCK1, ROCK2, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were enhanced accompanying the investigation arthritis-induced cognition deficits, which were remarkably down-regulated by salidroside and confirmed by the results obtained from western blot and immunohistochemistry. LC-MS/MS results ascertained that Sal could enter into the blood and brain tissues to exhibit the protective effect on arthritis-induced cognitive dysfunction. Therefore, it was assumed that Sal might be a potential therapeutic candidate to treat arthritis-induced brain cognition deficits through the regulation of Rho/ROCK/NF-κB signaling.
Renae L Smith-Ray
Full Text Available Background: Emerging literature suggests that mobility and cognition are linked. Epidemiological data support a negative association between cognition and falls among cognitively intact older adults. A small number of intervention studies found that regimented cognitive training (CT improves mobility among this population, suggesting that CT may be an under-explored approach toward reducing falls. To date, no studies have examined the impact of CT on balance among those who are cognitively impaired. The purpose of this study was to assess the feasibility of implementing a CT program among cognitively impaired older adults and examine whether there are potential improvements in balance following CT.Method: A single group repeated measures design was used to identify change in balance, depressive symptoms, and global cognition. A mixed method approach was employed to evaluate the feasibility of a CT intervention among a cohort of cognitively impaired older adults. CT was delivered in a group 2 days/week over 10 weeks using an online brain exercise program, Posit Science Brain HQ (20 hours. All participants completed a one-on-one data collection interview at baseline and post-program. Results: Participants (N=20 were on average 80.5 years old and had mild to moderate cognitive impairment. Following the 10-week cognitive training intervention, mean scores on 4 of the 5 balance measures improved among CT participants. Although none of the balance improvements reached significance, these findings are promising given the small sample size. Depressive symptoms significantly improved between baseline and 10 weeks (p=0.021. Mean global cognition also improved across the study period, but neither of these improvements were statistically significant. Based on participant responses, the CT program was feasible for this population.Conclusion: This study provides support for the feasibility of implementing a CT program among cognitively-impaired older adults
Seelye, Adriana; Hagler, Stuart; Mattek, Nora; Diane B Howieson; Wild, Katherine; Dodge, Hiroko H.; Kaye, Jeffrey A.
Introduction Subtle changes in cognitively demanding activities occur in mild cognitive impairment (MCI) but are difficult to assess with conventional methods. In an exploratory study, we examined whether patterns of computer mouse movements obtained from routine home computer use discriminated between older adults with and without MCI. Methods Participants were 42 cognitively intact and 20 older adults with MCI enrolled in a longitudinal study of in-home monitoring technologies. Mouse pointe...
Hick, R. F.; Botting, N.; Conti-Ramsden, G.
Background: The study is concerned with the cognitive abilities of children with specific language impairment (SLI). Previous research has indicated that children with SLI demonstrate difficulties with certain cognitive tasks despite normal non‐verbal IQ scores. It has been suggested that a general processing limitation might account for the pattern of language and cognitive difficulties seen in children with SLI. The performances on a visuo‐spatial short‐term memory task and a visuo‐spatial ...
Andressa de Oliveira Ferro
Full Text Available Abstract: Introduction: Stroke (CVA can generate motor, sensory and cognitive development deficits, affecting the individual’s performance in daily activities. Changes in any cognitive area can affect the individual’s occupational engagement. Objective: To evaluate the cognitive and functional capacity in patients suffering from stroke, showing the importance of cognitive assessment for occupational therapy intervention. Method: A comparative study with cross-sectional sampling of 44 subjects aged 30-80 years, both sexes. The subjects were divided in three groups: Adult: 11 individuals affected by stroke, 30-59 years old; Elderly: 10 individuals affected by stroke, 60-80 years old; Control: 23 normal subjects, 30-80 years old. Tests applied: MMSE, Clock Test, Test of tracks A and B, and functional capacity (BOMFAQ. Results: Cognitive changes were identified in the Adult and Elderly groups. The Adult group showed poorer performance on the Clock test (visuospatial and executive functions compared with the Control group. The Adult and Elderly groups presented worse performance in the Track A test (attention compared with the Control group. In the Track B test (visual attention, graphomotor skills, and mental flexibility, applied with absolute numbers, no significant differences were observed between the Adult and Elderly groups and the Control group, but cognitive impairment was perceived when the test was applied with categories. The Adult group showed higher prevalence of moderate/severe impairment in the carrying out of daily activities. Conclusion: As a rule, individuals suffering from stroke, in addition to having impaired functional capacity, present cognitive impairments that can negatively impact the performance of daily tasks, whether they are occupational, leisure or self-care activities. Accordingly, we observed the need to evaluate cognitive rehabilitation for better targeting and quality of life improvement.
Meltzer, Herbert Y; Rajagopal, Lakshmi; Huang, Mei; Oyamada, Yoshihiro; Kwon, Sunoh; Horiguchi, Masakuni
The N-methyl-D-aspartate receptor (NMDAR) antagonists, phencyclidine (PCP), dizocilpine (MK-801), or ketamine, given subchronically (sc) to rodents and primates, produce prolonged deficits in cognitive function, including novel object recognition (NOR), an analog of human declarative memory, one of the cognitive domains impaired in schizophrenia. Atypical antipsychotic drugs (AAPDs) have been reported to improve declarative memory in some patients with schizophrenia, as well as to ameliorate and prevent the NOR deficit in rodents following scNMDAR antagonist treatment. While the efficacy of AAPDs to improve cognitive impairment in schizophrenia (CIS) is limited, at best, and controversial, single doses of all currently available AAPDs so far tested transiently restore NOR in rodents following scNMDAR antagonist treatment. Typical antipsychotic drugs (APDs), e.g. haloperidol and perphenazine, are ineffective in this rodent model, and may be less effective as treatments of some domains of CIS. Serotonergic mechanisms, including, but not limited to serotonin (5-HT)2A and 5-HT7 antagonism, 5-HT(1A), and GABA(A) agonism, contribute to the efficacy of the AAPDs in the scNMDAR antagonist rodent models, which are relevant to the loss of GABA interneuron/hyperglutamate hypothesis of the etiology of CIS. The ability of sub-effective doses of the atypical APDs to ameliorate NOR in the scNMDAR-treated rodents can be restored by the addition of a sub-effective dose of the 5-HT(1A) partial agonist, tandospirone, or the 5-HT7 antagonist, SB269970. The mGluR2/3 agonist, LY379268, which itself is unable to restore NOR in the scNMDAR-treated rodents, can also restore NOR when given with lurasidone, an AAPD. Enhancing cortical and hippocampal dopamine and acetylcholine efflux, or both, may contribute to the restoration of NOR by the atypical APDs. Importantly, co-administration of lurasidone, tandospirone, or SB269970, with PCP, to rodents, at doses 5-10 fold greater than those
Tröster, Alexander I
Cognitive changes of Parkinson's disease (PD) manifest earlier and are more heterogeneous than previously appreciated. Approximately one-third of patients have at least mild cognitive changes at PD diagnosis, and subtle changes might be appreciable among those at risk for PD. Executive dysfunction is the most common cognitive change, but other phenotypes exist. Pathobiologic and potential prognostic differences among cognitive phenotypes remain poorly understood. Progress in the neuropsychology, epidemiology and pathobiology of mild cognitive impairment (MCI) in PD is hampered by lack of diagnostic criteria. This study proposes preliminary research criteria for two categories of PD non-dementia cognitive impairment.
Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong
Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.
Gerstenecker, Adam; Mast, Benjamin; Duff, Kevin; Ferman, Tanis J.; Litvan, Irene
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
Chang, Jason Y; Tsai, Pao-Feng; Woods, Sheery; Beck, Cornelia; Roberson, Paula K; Rosengren, Karl
This article describes the authors' experience and strategies in teaching Tai Chi, a gentle exercise derived from an ancient Chinese martial art, to mildly cognitively impaired elders to relieve osteoarthritic knee pain. The 12-form Sun-style Tai Chi, a set of Tai Chi forms endorsed by the American Arthritis Foundation, was used in the program. Teaching Tai Chi to elders with mild cognitive impairment requires particular strategies tailored to their physical and cognitive frailty. When effectively taught, Tai Chi can be a unique and cost-effective intervention for elders with knee pain caused by osteoarthritis.
Differentiating mild cognitive impairment (MCI) from dementia is important, as treatment options differ. There are few short (<5 min) but accurate screening tools that discriminate between MCI, normal cognition (NC) and dementia, in the Dutch language. The Quick Mild Cognitive Impairment (Qmci) screen is sensitive and specific in differentiating MCI from NC and mild dementia. Given this, we adapted the Qmci for use in Dutch-language countries and validated the Dutch version, the Qmci-D, against the Dutch translation of the Standardised Mini-Mental State Examination (SMMSE-D).
Andersen, Rune; Fagerlund, B; Rasmussen, Hans
BACKGROUND: Impaired cognition is a prominent feature of schizophrenia. To what extent the heterogeneous cognitive impairments can be accounted for by considering only a single underlying impairment or a small number of core impairments remains elusive. This study examined whether cognitive...... of neuropsychological tests to assess domains of cognitive impairments in schizophrenia. Composite scores were calculated, grouping tests into cognitive domains. RESULTS: There were significant differences between patients and healthy controls on global cognition and all cognitive domains, including verbal intelligence......, processing speed, sustained attention, working memory, reasoning and problem solving, verbal learning and memory, visual learning and memory, and reaction time. All these significant differences, except for verbal intelligence and global cognition, disappeared when processing speed was included...
Zuo, Z-F; Wang, W; Niu, L; Kou, Z-Z; Zhu, C; Wang, W; Zhao, X-H; Luo, D-S; Zhang, T; Zhang, F-X; Liu, X-Z; Wu, S-X; Li, Y-Q
Diabetic cognitive dysfunction (DCD), usually accompanied with chronically elevated glucocorticoids and hippocampal astrocytic alterations, is one of the most serious complications in patients with type-1 diabetes. However, the role for chronically elevated glucocorticoids and hippocampal astrocytic activations in DCD remains to be elucidated, and it is not clear whether astrocytic N-myc downstream-regulated gene 2 (NDRG2, involved in cell differentiation and development) participated in DCD. In the present study, three months after streptozotocin (STZ)-induced type-1 diabetes onset, rats showed cognitive impairments in Morris water maze test as well as elevated corticosterone level. Diabetic rats also presented down-regulation of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and NDRG2 in hippocampus revealed by immunohistochemistry staining, real-time PCR and Western blot. Moreover, the diabetic cognitive impairments were ameliorated by 9-day glucocorticoids receptor (GR) blockade with RU486, and the down-regulation of hippocampal NDRG2 and GFAP in diabetic animals was also attenuated by 9-day GR blockade. These results suggest that glucocorticoids-GR system is crucial for DCD, and that astrocytic reactivity and NDRG2 are involved in these processes. Thus, inhibiting GR activation in the hippocampus may be a novel therapeutic strategy for treating DCD.
Lawrence, Blake J.; Gasson, Natalie; Loftus, Andrea M.
The current study examined the prevalence and subtypes of Mild Cognitive Impairment (MCI) in an Australian sample of people with Parkinson’s Disease (PD). Seventy participants with PD completed neuropsychological assessments of their cognitive performance, using MDS Task Force Level II diagnostic criteria for PD-MCI. A cut-off score of less than one standard deviation (SD) below normative data determined impaired performance on a neuropsychological test. Of 70 participants, 45 (64%) met Level II diagnostic criteria for PD-MCI. Among those with PD-MCI, 42 (93%) were identified as having multiple domain impairment (28 as amnestic multiple domain and 14 as nonamnestic multiple domain). Single domain impairment was less frequent (2 amnestic/1 nonamnestic). Significant differences were found between the PD-MCI and Normal Cognition groups, across all cognitive domains. Multiple domain cognitive impairment was more frequent than single domain impairment in an Australian sample of people with PD. However, PD-MCI is heterogeneous and current prevalence and subtyping statistics may be an artifact of variable application methods of the criteria (e.g., cut off scores and number of tests). Future longitudinal studies refining the criteria will assist with subtyping the progression of PD-MCI, while identifying individuals who may benefit from pharmacological and nonpharmacological interventions. PMID:27650569
Full Text Available Forensic settings demand expedient and conclusive forensic psychological assessment. The aim of this study was to design a simple and fast, but reliable psychometric instrument for detecting the malingering of cognitive impairment. In a quasi-experimental design, 156 individuals were divided into three groups: a normal group with no cognitive impairment; a Mild Cognitive Impairment (MCI group; and a group of informed malingerers with no MCI who feigned cognitive impairment. Receiver Operating Curve (ROC analysis of the Test of Memory Malingering (TOMM, and of several subtests of the Wechsler Memory Scale (WMS-III revealed that the WMS-III was as reliable and accurate as the TOMM in discriminating malingerers from the honest. The results revealed that the diagnostic accuracy, sensitivity and specificity of the WMS-III Auditory Recognition Delayed of Verbal Paired Associates subtest was similar to the TOMM in discriminating malingering from genuine memory impairment. In conclusion, the WMS-III Recognition of Verbal Paired Associates subtest and the TOMM provide a fast, valid and reliable screening method for detecting the malingering of cognitive impairment.
Goikolea, José M.; Bonnin, Caterina M.; Sarró, Salvador; Segura, Barbara; Amann, Benedikt L.; Monté, Gemma C.; Moro, Noemi; Fernandez-Corcuera, Paloma; Maristany, Teresa; Salvador, Raymond; Vieta, Eduard; Pomarol-Clotet, Edith; McKenna, Peter J.
Introduction Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain. Methods Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task. Results No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls. Conclusions Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function. PMID:27448153
Potrata, B; Cavet, J; Blair, S; Howe, T; Molassiotis, A
The aim of this study was to obtain a more in-depth understanding of cognitive impairments and concerns as described by patients with multiple myeloma and the strategies used to cope with them. Semi-structured qualitative interviews were undertaken with 15 multiple myeloma patients of differing age ranges and at various stages of their disease. Various cognitive impairments, such as problems with short-term memory, poor recall and lack of concentration were observed and/or expressed in at least 10 out of 15 patients, all of them long(er)-term survivors. In some patients cognitive impairments significantly interfered with their personal and professional lives, and for some patients these were described as permanent. The patients used various coping strategies, from denial, taking notes, writing diaries, reading simpler texts, using talking books and videos, to using systems for counting medication to cope with the results of their cognitive impairment. Our findings differ from much of the contemporary literature which states that if cognitive impairments in cancer patients occur, they are mostly mild and transient. More proactive supportive care is needed to help patients with multiple myeloma to cope with poorer cognitive functioning.
Arvanitakis, Zoe; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue E; Barnes, Lisa L; Bennett, David A
Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.
Background: There is a considerable body of evidence to suggest that behavioural activation for depression is an equally effective but less complex treatment than cognitive behavioural therapy. It may therefore be more suitable for those who are cognitively impaired (i.e. early-stage dementia or mild cognitive impairment) or have a learning…
Algarabel, Salvador; Sales, Alicia; Pitarque, Alfonso; Meléndez, Juan C; Escudero, Joaquín; Mayordomo, Teresa
This study aims to analyze implicit and explicit memory performance as a function of cognitive reserve (CR) in a healthy control group (N = 39) and a mild cognitive impairment (MCI) group (N = 37). Both groups were subdivided into high and low cognitive reserve, and were asked to complete an explicit and implicit associative recognition tasks. The results showed that the control group was able to learn both tasks (η2 = .19, p association task. Participants diagnosed with MCI showed little plasticity in learning associations regardless of CR (η2 = .12, p < .01).
Full Text Available Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate. Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Results: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64, 1.67 (1.09-2.57, and 2.49 (1.07-5.77, respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39. Conclusion: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients.
Yan, Tingxu; Shang, Lei; Wang, Mengshi; Zhang, Chenning; Zhao, Xu; Bi, Kaishun; Jia, Ying
The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging-associated neurodegenerative diseases.
Li, Xiaohang; Cui, Jin; Yu, Yang; Li, Wei; Hou, Yujun; Wang, Xin; Qin, Dapeng; Zhao, Cun; Yao, Xinsheng; Zhao, Jian; Pei, Gang
Decline of cognitive function is the hallmark of Alzheimer's disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.
Full Text Available Decline of cognitive function is the hallmark of Alzheimer's disease (AD, regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ reduction activity to identify active constituent(s of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1 and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP. Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.
Laitusis, Cara Cahalan; Maneckshana, Behroz; Monfils, Lora; Ahlgrim-Delzell, Lynn
The purpose of this study was to examine Differential Item Functioning (DIF) by disability groups on an on-demand performance assessment for students with severe cognitive impairments. Researchers examined the presence of DIF for two comparisons. One comparison involved students with severe cognitive impairments who served as the reference group…
Harris, Paula; Fernandez Suarez, Marcos; Surace, Ezequiel I; Chrem Méndez, Patricio; Martín, María Eugenia; Clarens, María Florencia; Tapajóz, Fernanda; Russo, Maria Julieta; Campos, Jorge; Guinjoan, Salvador M; Sevlever, Gustavo; Allegri, Ricardo F
Background The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer’s disease, and in control subjects. Methods Thirty-three participants from the Argentina-Alzheimer’s Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. Results The CRQ significantly correlated with TAP-BA, education, and Aβ1-42. When considering Aβ1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aβ1-42 were associated with higher CRQ scores. Conclusion Reduced Aβ1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer’s disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aβ1-42 levels in individuals with more cognitive reserve. PMID:26504392
Full Text Available In an effort to accommodate MOCA to better fit for the Chinese context, this study was designed to employ the MOCA criteria to screen mild cognitive impairment (MCI and analyze associated risk factors in military retirees.Three hundred and four retired military cadres were recruited using a random cluster sampling technique with information collected including personal, prevalence, MOCA scale, and related neuropsychiatry scale. Thirty retirees were randomly chosen to be further analyzed one month later using the revised MOCA scale.①Our data indicated an incidence rate of 64.8% for mild cognitive impairment in retired military cadres. The incidence rate for MCI was significantly higher in those aged 80 or above compared with those 80 years of age or younger (P<0.05. The incidence rate of MCI was significantly higher in those with fewer than 6 years of education compared with those with over 7 years of education (P<0.05. The MCI incidence was higher for those with little exercise than those taking regular exercise (P<0.01. Moreover, the MCI incidence was higher in stroke patients than those who never had a stroke episode (P<0.05. ②There was a significant correlation between MOCA and MMSE scale scores (r = 0.81. MOCA scale scores were negatively correlated with ADL and CES-D scores (although not PSQI scores. ③ MOCA recension Cronbach's alpha value was 0.862. The related coefficient of MOCA and MOCA recension was 0.878(P<0.01. When the Score of cut-off -point of the MOCA recension was 28, the area in ROC curve analyses was 0.859, as well as the largest area.Retired cadres exhibited a greater incidence of MCI (than general population, which was closely associated with age, level of education and physical exercise and cerebral apoplexy. Revised MOCA scale displays a better validity and reaction degree of reliability and is more suitable for screening and diagnosis of MCI in the elderly in China.
Chang, Yu-Ling; Chen, Ta-Fu; Shih, Yao-Chia; Chiu, Ming-Jang; Yan, Sui-Hing; Tseng, Wen-Yih Isaac
Amnestic mild cognitive impairment (aMCI), which has a high risk of progression to Alzheimer's disease (AD), can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. We investigated the integrity of regional gray matter and segments of the cingulum bundle with diffusion spectrum imaging tract-specific analysis, and their relationships to neuropsychological functioning, in 46 individuals with aMCI (S-aMCI n = 24; M-aMCI n = 22) and 36 healthy controls (HC). Results demonstrated that although both aMCI groups were impaired on all memory measures relative to HCs, the M-aMCI group demonstrated worse performance on paired association memory and on selective executive function relative to the S-aMCI group. The two aMCI groups did not show significant atrophy in regional gray matter indices as compared to the HC group, but the M-aMCI group showed significant disruption in white matter of the left anterior and inferior cingulum bundles relative to the S-aMCI and HC groups. Furthermore, disruption in the inferior cingulum bundles was significantly associated with executive function and attention/processing speed in all aMCI participants above and beyond the contribution of bilateral hippocampal volumes. Overall, these results indicate that the degeneration of cingulum fibers did not appear to arise from degeneration of the corresponding cerebral cortex. It also suggests relatively greater sensitivity of a white matter biomarker and comprehensive neuropsychological evaluation over gray matter biomarkers in early detection of AD.
Full Text Available Impaired cognition increases mortality in the aged. It is unclear how dietary quality might affect this relationship.To examine how dietary diversity and cognition might interact to determine survival.In a Nutrition and Health Survey in Taiwan (NAHSIT 1999–2000, 1,839 representative elderly were followed for mortality up to 10 years. The dietary quality measure was a dietary diversity score (DDS, range: 0–6 to present six food groups (dairy, meat, rice and grains, fruit, vegetable,fat and oil derived from a 24-h dietary recall. Cognitive function was evaluated by the validated Short Portable Mental Status Questionnaire (SPMSQ.Those with cognitive impairment (SPMSQ ≥ 3 errors had 2.56 (95% confidence intervals (CI, 1.99–3.28 times the all-cause-mortality risk of those with intact cognition. After control for potential confounders, the adjusted hazard ratio (HR remained significant (1.46, 95% CI: 1.06–2.02. Significant interactions for DDS and cognition were found (p<0.001. Jointly, compared to normal-SPMSQ-highest DDS, the greatest HR is where impaired cognition is combined with the lowest DDS (HR 2.24, 95% CI: 1.19–4.24. Increased DDS was associated with improvement in survival that is especially evident in those with 1–2 errors where the greatest HR reduction was found, and for fruit. Attributability for mortality amounted to 18% for impaired cognition and 33% for least diverse diet.Dietary diversity may improve survival in relation to impaired cognitive function.
Kurt A. Jellinger
Full Text Available Vascular cognitive impairment describes a continuum of cognitive diorders ranging from mild cognitive impairment to dementia, in which vascular brain injury involving regions important for memory, cognition and behaviour plays an important role. Classification, prevalence, and pathophysiology are a matter of current research. Clinical diagnostic criteria show moderate sensitivity (ca 50% and variable specificity (range 64-98%. In Western clinical series, VaD is suggested in 8-10% of cognitively impaired elderly subjects. Its prevalence in autopsy series varies from 0.03 to 58%. In contrast to Alzheimer disease (AD and mixed dementia showing significant age-related increase, the prevalence of VaD significantly decreases after age 80 years. Cognitive decline is commonly associated with widespread small ischemic vascular lesions involving subcortical brain areas. The lesions affect neuronal networks involved in cognition, memory, and behavior.Cerebrovascular lesions (CVLs often coexist wth Alzheimer-type lesions and other pathologies. The lesion pattern of "pure" VaD differs from that in mixed dementia (AD + CVLs, which suggests different pathogenesis of both phenotypes. Minor CVLs appear not essential for cognitive impairment in full-blown AD, while both mild AD-type pathology and small vessel disease may interact synergistically in promoting and progressing dementia. However, both AD-related and vascular brain pathologies have been reported.Despite recent suggestions for staging and grading CVLs in specific brain areas, no validated neuropathological criteria are currently available for VaD and mixed dementia. Further clinico-pathological studies and harmonization of neuropathological procedures are needed to validate the diagostic criteria for VaD and mixed dementia in order to clarify the impact of CVLs and other coexistent pathologies on cognitive impairment as a basis for further successful therapeutic options.
Full Text Available Kazuki Uemura,1,3 Hiroyuki Shimada,1 Hyuma Makizako,1,3 Takehiko Doi,1 Daisuke Yoshida,1 Kota Tsutsumimoto,1 Yuya Anan,1 Takao Suzuki21Section for Health Promotion, Department for Research and Development to Support Independent Life of Elderly, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, 2Research Institute, National Center for Geriatrics and Gerontology, Aichi, 3Japan Society for the Promotion of Science, Tokyo, JapanBackground: Although much evidence supports the hypothesis that cognitive function and physical function are interrelated, it is unclear whether cognitive decline with mild cognitive impairment influences trainability of physical performance in exercise intervention. The purpose of this study was to examine the association between cognitive function at baseline and change in physical performance after exercise intervention in older adults with mild cognitive impairment.Methods: Forty-four older adults diagnosed with mild cognitive impairment based on the Peterson criteria (mean age 74.8 years consented to and completed a 6-month twice weekly exercise intervention. The Timed Up and Go (TUG test was used as a measure of physical performance. The Mini-Mental State Examination (MMSE, Trail Making Test Part B, Geriatric Depression Scale, baseline muscle strength of knee extension, and attendance rate of intervention, were measured as factors for predicting trainability.Results: In the correlation analysis, the change in TUG showed modest correlations with attendance rate in the exercise program (r = -0.354, P = 0.027 and MMSE at baseline (r = -0.321, P = 0.034. A multiple regression analysis revealed that change in TUG was independently associated with attendance rate (ß = -0.322, P = 0.026 and MMSE score (ß = -0.295, P = 0.041, controlling for age and gender.Conclusion: General cognitive function was associated with improvements in physical performance after exercise intervention in
Screening of cognitive impairment in patients with Parkinson's disease: diagnostic validity of the Brazilian versions of the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised
Full Text Available ABSTRACTObjective The aim of the present study is to examine the accuracy of the Brazilian versions of the Montreal Cognitive Assessment (MoCA and the Addenbrooke's Cognitive Examination-Revised (ACE-R to screen for mild cognitive impairment (PDMCI and dementia (PDD in patients with Parkinson's disease (PD.Method Both scales were administered to a final convenience sample of 79 patients with PD. Patients were evaluated by a neurologist, a psychiatrist and a neuropsychologist using UPDRS, Hoehn and Yahr and Schwab and England scales, global deterioration scale, a psychiatric structured interview, Mattis Dementia Rating Scale and other cognitive tests.Results There were 32 patients with PDMCI and 17 patients with PDD. The MoCA and the ACE-R were able to discriminate patients with PDD from the others.Conclusion Both scales showed to be useful to screen for dementia but not for mild cognitive impairment in patients with PD.
McCade, Donna; Savage, Greg; Guastella, Adam; Lewis, Simon J G; Naismith, Sharon L
Emotion recognition is impaired in dementia and there is some initial evidence to suggest that milder deficits may be present in Mild Cognitive Impairment (MCI) patients, an "at risk" population for transition to dementia. In this study, we investigated the emotion recognition profile of MCI subgroups. Results show emotion recognition deficits exist for the amnestic subtype with impairment in multiple domains, with an emotion-specific deficit for anger recognition. Impaired emotion recognition in aMCI was independent of patient mood and cognitive deficits. The study is the first to examine the nonamnestic subtype. No emotion recognition deficits were found. This finding is surprising given the association between the nonamnestic subtype and frontal systems dysfunction. Impaired emotion recognition could be related to the selective pathophysiology in neural pathways, particularly the temporal lobe and connected limbic and prefrontal regions, implicated in both aMCI and emotion processing. These findings may have implications for early diagnosis, prognosis, and clinical management.
Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment.
Lee, Song Hee; Choi, Bo Young; Kim, Jin Hee; Kho, A Ra; Sohn, Min; Song, Hong Ki; Choi, Hui Chul; Suh, Sang Won
Choline alfoscerate (α-GPC) is a common choline compound and acetylcholine precursor in the brain, which has been shown to be effective in the treatment of Alzheimer's disease and dementia. α-GPC has been shown to enhance memory and cognitive function in stroke and Alzheimer's patients but currently remains untested in patients suffering from epilepsy. This study aimed to evaluate whether α-GPC treatment after seizure can ameliorate seizure-induced cognitive impairment and neuronal injury. The potential therapeutic effects of α-GPC on seizure-induced cognitive impairment were tested in an animal model of pilocarpine-induced seizure. Seizures were induced by intraperitoneal injection of pilocarpine (25mg/kg) in male rats. α-GPC (250mg/kg) was injected into the intramuscular space once daily for one or three weeks from immediately after seizure, or from 3 weeks after the seizure onset for 3 weeks. Here we found that immediate 1-week treatment of α-GPC showed no neuroprotective effects and neurogenesis. Immediate 3-week treatment of α-GPC showed neuroprotective effect but no effect on neurogenesis. To evaluate the effect of late treatment of α-GPC on cognitive impairment following seizure, rats were injected α-GPC from 3 weeks after seizure for 3 weeks and subjected to a water maze test. In the present study, we found that administration of α-GPC starting at 3 weeks after seizure improved cognitive function through reduced neuronal death and BBB disruption, and increased neurogenesis. Therefore, α-GPC injection may serve as a beneficial treatment for improvement of cognitive function in epilepsy patients.
Patients with lacunar infarcts are thought tohave an increased risk of cognitive i mpair ment anddementia.Cognitive i mpair ment is a predictor ofpoor functional outcome in stroke survivors.However,in patients with lacunar infarcts,thepathway leading to cognitive i mpair ment is notclear.According to the lacunar hypothesis,cogni-tive i mpair ment results fromincreased number andvolume of lacunes,especially whenlocated strategi-cally within frontal subcortical loops;while Feinet alfound that cogn...
Spikman, Jacoba M.; Timmerman, Marieke E.; Milders, Maarten V.; Veenstra, Wencke S.; van der Naalt, Joukje
Impairments in social behavior are frequently found in moderate to severe traumatic brain injury (TBI) patients and are associated with an unfavorable outcome with regard to return to work and social reintegration. Neuropsychological tests measuring aspects of social cognition are thought to be sens
Lamoth, Claudine; Appels, Bregje; Van Campen, Jos
Objective: For persons with dementia performance of a cognitive task during a motor task is associated with impaired gait stability and increased fall risk. While gait with and without dual tasking has often been the object studies, few studies have investigated the relationship between different co
Nybo, M; Olsen, H; Jeune, B;
these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p ... higher SAP concentration (60.2 microg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4+/-9.3 microg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive...... performance had significantly increased plasma concentrations of SAP, while the values for cognitive intact centenarians were within the normal range....
Conclusions: These findings indicated that WMS-III and WAIS-R can differentiate patients with refractory temporal lobe epilepsy from normal subjects. However, the obtained cognitive profile could not differentiate between the right and the left TLE.
Full Text Available Introduction: pain is a frequent and relevant problem in children with severe cognitive impairments. Assessing pain in these patients can be difficult. Specific observational tools such as the Collignon Giusiano Questionnaire or the Non-communicating Children’s Pain Checklist ( NCCPC are available, but their use is not widespread. Children with severe cognitive impairment are frequently in need of painful procedures but data about availability of procedural sedation in this setting are limited. Objective of the study: to evaluate paediatricians’ attitudes toward pain in children with severe cognitive impairment by measuring the use of specific pain scales and the use of analgesia or procedural sedation in course of a frequent procedure such as botulinum toxin injection. Methods: phone interview with the doctor on duty of 56 paediatric wards in 3 regions of the North East of Italy, addressing the routine use of pain scales, and the use of specific observational tools for non communicating children. A phone interview was also conducted in 4 centers routinely practicing botulinum toxin injection about the use of analgesia or procedural sedation. Results: 1 centre out of 55 reported to use specific scales for children with cognitive impairment, specifically the Collignon Giusiano Questionnaire. No centre used procedural sedation for botulinum toxin injection. Conclusion: in the investigated area there is a lack of attention to pain in children with severe cognitive impairment. Specific educational efforts should be done to improve the quality of care in this setting.
Full Text Available Obstructive sleep apnea-hypopnea syndrome (OSAHS is a common sleep-related breathing disorder that is associated with significant morbidity and mortality. It has received increasing attention that neurocognitive deficits occur with a high frequency in OSAHS. However, it is rarely known that OSAHS impacts on cognition in the elderly in whom an increased prevalence of OSAHS is present. In this review we consider recent studies in the association between OSAHS and cognitive impairments, with specific interest in the older population. Firstly, we elucidate the characteristics of OSAHS and OSAHS-related cognitive impairments in the older patients. Many studies have showed that the prevalence of OSAHS increases with age and it is higher in the elderly than other population. Moreover, OSAHS is associated with higher incidence of comorbidities and increased risk of clinical deterioration in the elderly, especially the neurocognitive impairments which even can develop dementia. Subsequently, we discuss the possible reasons of cognitive impairments that caused or aggravated by OSAHS in the elderly. The intermittent hypoxia (IH-related disturbances of homeostasis such as oxidative stress, inflammation, and age-related changes such as the changes of sleep architecture, the declined expression level of anti-aging gene, medical comorbidities and polypharmacy, may be both contribute to the increased risk of cognitive impairments in the older patients with OSAHS.
Zhu, Runxiu; Yan, Zhongrui; Zheng, Shouhuan; Wang, Jingwei; Huo, Jia; Liu, Yunlin; Li, Xin; Ji, Yong
To investigate potential associations between carotid artery stenosis and cognitive impairment among patients with acute ischemic stroke and to provide important clinical implications. We measured the degree of carotid artery stenosis and recorded the Mini-Mental State Examination score (MMSE) at admission in 3116 acute ischemic stroke patients. The association between carotid stenosis and cognitive impairment assessed by MMSE was tested using multivariate regression analysis. Other clinical variables of interest were also studied. After adjusting for age, gender, education level, marriage, alcohol use, tobacco use, physical activity, hypertension, diabetes, hypercholesterolemia, atrial fibrillation, myocardial infarction and NIHSS (National Institutes of Health Stroke Scale) score, we found that participants with high-grade stenosis of the carotid artery had a higher likelihood of cognitive impairment compared to those without carotid artery stenosis (OR = 1.49, 95%CI: 1.05–2.11, p<0.001). Left common carotid artery stenosis was associated with cognitive impairment in the univariate analysis, although this effect did not persist after adjustment for the NIHSS score. Cognitive impairment was associated with high-grade stenosis of the right carotid artery. PMID:26751070
Maria Lazarevna Chukhlovina
Full Text Available Objective: to evaluate cognitive functions and drug correction of identified impairments in heroin users. Patients and methods. Thirty-two patients (7 women and 25 men aged 18 to 45 years who had used heroin for 1—3 years were examined using the mini-mental state examination (MMSE, the techniques of «memorizing words» and «excluding words», the tests of «information-memory-concentration», quantitative assessment of clock drawing, and the frontal assessment battery. The detected cognitive impairments were corrected with the standardized Ginkgo Biloba extract (EGb 761 ®, Tanakan ®. Results. Cognitive impairments were found in all the patients: moderate cognitive disorders in 68.8% and mild dementia in 31.2%; thinking disorders were most noticeable; decreased attention, frontal lobe dysfunction, and visual spatial impairments were detectable. After a course of therapy with tanakan (120—240 g/day according to the degree of cognitive impairments for 3 months, there was a significant improvement in MMSE scores, thought, concentration, memory; however, they failed to achieve the scores in the control group consisting of 10 apparently healthy individuals of the same age and sex.
Full Text Available To investigate potential associations between carotid artery stenosis and cognitive impairment among patients with acute ischemic stroke and to provide important clinical implications. We measured the degree of carotid artery stenosis and recorded the Mini-Mental State Examination score (MMSE at admission in 3116 acute ischemic stroke patients. The association between carotid stenosis and cognitive impairment assessed by MMSE was tested using multivariate regression analysis. Other clinical variables of interest were also studied. After adjusting for age, gender, education level, marriage, alcohol use, tobacco use, physical activity, hypertension, diabetes, hypercholesterolemia, atrial fibrillation, myocardial infarction and NIHSS (National Institutes of Health Stroke Scale score, we found that participants with high-grade stenosis of the carotid artery had a higher likelihood of cognitive impairment compared to those without carotid artery stenosis (OR = 1.49, 95%CI: 1.05-2.11, p<0.001. Left common carotid artery stenosis was associated with cognitive impairment in the univariate analysis, although this effect did not persist after adjustment for the NIHSS score. Cognitive impairment was associated with high-grade stenosis of the right carotid artery.
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.
This article reviews the clinical and experimental researches on cognitive impairment related to diabetes in the recent decade. Most clinical studies indicate that the cognitive impairment in patients with type 1 diabetes mellitus is related to recurrent hypoglycemia closely. There is little research about whether or not hyperglycemia is related to cognitive impairment in patients with type 1 diabetes mellitus. Most studies indicate that the cognitive impairment in type 2 diabetes involves multiple factors through multiple mechanisms, including blood glucose, blood lipid, blood pressure, level of insulin, medication, chronic complication, etc. But, there has been no large-scale, multi-center, randomized controlled clinical trial in China recently. And what is more, some problems exist in this field of research, such as the lack of golden criterion of cognitive function measurement, different population of studied objects, and incomprehensive handling of confounding factors. Experimental studies found that hippocampal long-term potentiation (LTP) was impaired,which were manifested by impairment of spatial memory and decreased expression of LTP, but its relation to hyperglycemia, the duration of diabetes, learning and memory has always been differently reported by different researches. Thus, there are a lot of unknown things to be explored and studied in order to clarify its mechanism. TCM has abundant clinical experience in treating cerebral disease with medicine that enforces the kidney and promotes wit. However, there has been no research on treating diabetic cognitive impairment,which requires work to be done actively and TCM to be put into full play, in order to improve the treatment of diabetes and enhance living quality of patients.
Moran, G M; Fletcher, B; Feltham, M G; Calvert, M; Sackley, C; Marshall, T
Transient ischaemic attack (TIA) and minor stroke are characterized by short-lasting symptoms; however, anecdotal and empirical evidence suggests that these patients experience ongoing cognitive/psychological impairment for which they are not routinely treated. The aims were (i) to investigate the prevalence and time course of fatigue, anxiety, depression, post-traumatic stress disorder(PTSD) and cognitive impairment following TIA/minor stroke; (ii) to explore the impact on quality of life (QoL), change in emotions and return to work; and (iii) to identify where further research is required and potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the Cochrane libraries and the grey literature between January 1993 and April 2013 was undertaken. Literature was screened and data were extracted by two independent reviewers. Studies were included of adult TIA/minor stroke participants with any of the outcomes of interest: fatigue, anxiety, depression, PTSD, cognitive impairment, QoL, change in emotions and return to work. Random-effects meta-analysis pooled outcomes by measurement tool. Searches identified 5976 records, 289 were assessed for eligibility and 31 studies were included. Results suggest high levels of cognitive impairment and depression post-TIA/minor stroke which decreased over time. However, frequencies varied between studies. Limited information was available on anxiety, PTSD and fatigue. Meta-analysis revealed that the measurement tool administered influenced the prevalence of cognitive impairment: Mini-Mental State Examination 17% [95% confidence interval (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that TIA/minor stroke patients may experience residual impairments; however, results should be interpreted with caution because of the few high quality studies. Notwithstanding, it is important to raise awareness
Sweeney-Reed, Catherine M; Riddell, Patricia M; Ellis, Judi A; Freeman, Jayne E; Nasuto, Slawomir J
The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer's disease, which has been described as a 'disconnection syndrome'.
Catherine M Sweeney-Reed
Full Text Available The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer's disease, which has been described as a 'disconnection syndrome'.
Full Text Available OBJECTIVES: To investigate the presence and the nature of cognitive impairment in a large sample of patients with Multiple Sclerosis (MS, and to identify clinical and demographic determinants of cognitive impairment in MS. METHODS: 303 patients with MS and 279 healthy controls were administered the Brief Repeatable Battery of Neuropsychological tests (BRB-N; measures of pre-morbid verbal competence and neuropsychiatric measures were also administered. RESULTS: Patients and healthy controls were matched for age, gender, education and pre-morbid verbal Intelligence Quotient. Patients presenting with cognitive impairment were 108/303 (35.6%. In the overall group of participants, the significant predictors of the most sensitive BRB-N scores were: presence of MS, age, education, and Vocabulary. The significant predictors when considering MS patients only were: course of MS, age, education, vocabulary, and depression. Using logistic regression analyses, significant determinants of the presence of cognitive impairment in relapsing-remitting MS patients were: duration of illness (OR = 1.053, 95% CI = 1.010-1.097, p = 0.015, Expanded Disability Status Scale score (OR = 1.247, 95% CI = 1.024-1.517, p = 0.028, and vocabulary (OR = 0.960, 95% CI = 0.936-0.984, p = 0.001, while in the smaller group of progressive MS patients these predictors did not play a significant role in determining the cognitive outcome. CONCLUSIONS: Our results corroborate the evidence about the presence and the nature of cognitive impairment in a large sample of patients with MS. Furthermore, our findings identify significant clinical and demographic determinants of cognitive impairment in a large sample of MS patients for the first time. Implications for further research and clinical practice were discussed.
Yoo, Doo Han; Lee, Jae Shin
[Purpose] This study examined the clinical usefulness of the clock drawing test applying Rasch analysis for predicting the level of cognitive impairment. [Subjects and Methods] A total of 187 stroke patients with cognitive impairment were enrolled in this study. The 187 patients were evaluated by the clock drawing test developed through Rasch analysis along with the mini-mental state examination of cognitive evaluation tool. An analysis of the variance was performed to examine the significance of the mini-mental state examination and the clock drawing test according to the general characteristics of the subjects. Receiver operating characteristic analysis was performed to determine the cutoff point for cognitive impairment and to calculate the sensitivity and specificity values. [Results] The results of comparison of the clock drawing test with the mini-mental state showed significant differences in according to gender, age, education, and affected side. A total CDT of 10.5, which was selected as the cutoff point to identify cognitive impairement, showed a sensitivity, specificity, Youden index, positive predictive, and negative predicive values of 86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is believed to be useful in assessments and interventions based on its excellent ability to identify cognitive disorders.
Leaver, Katherine; Poston, Kathleen L
Many patients with Parkinson's disease (PD) will develop cognitive impairment. Cross-sectional studies have shown that certain protein levels are altered in the cerebrospinal fluid (CSF) of PD patients with dementia and are thought to represent potential biomarkers of underlying pathogenesis. Recent studies suggest that CSF biomarker levels may be predictive of future risk of cognitive decline in non-demented PD patients. However, the strength of this evidence and difference between specific CSF biomarkers is not well delineated. We therefore performed a systematic review to assess if levels of specific CSF protein biomarkers are predictive of progression to cognitive impairment. Nine articles were identified that met inclusion criteria for the review. Findings from the review suggest a convergence of evidence that a low baseline Aβ42 in the CSF of non-demented PD patients predicts development of cognitive impairment over time. Conversely, there is limited evidence that CSF levels of tau, either total tau or phosphorylated tau, is a useful predictive biomarker. There are mixed results for other CSF biomarkers such as α-synuclein, Neurofilament light chain, and Heart fatty acid-binding protein. Overall the results of this review show that certain CSF biomarkers have better predictive ability to identify PD patients who are at risk for developing cognitive impairment. Given the interest in developing disease-modifying therapies, identifying this group will be important for clinical trials as initiation of therapy prior to the onset of cognitive decline is likely to be more efficacious.
Zhu, Zhiyuan; Li, Chenjing; Wang, Xu; Yang, Zhengyi; Chen, Jing; Hu, Lihong; Jiang, Hualiang; Shen, Xu
Alzheimer's disease (AD) characterizes a progressive neurodegenerative disorder of the brain, while AD patients are afflicted with irreversible loss of neurons and further the intellectual abilities including memory and reasoning. One of the typical hallmarks of AD is the deposition of senile plaque that is contributed mainly by amyloid-beta (Abeta), whose production is initiated by beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1). Inhibition of BACE1 is thereby regarded as an attractive strategy for anti-AD drug discovery. Here, we reported that the natural product 2,2',4'-trihydroxychalcone (TDC) from Glycyrrhiza glabra functioned as a specific non-competitive inhibitor against BACE1 enzyme, and potently repressed beta-cleavage of APP and production of Abeta in human embryo kidney cells-APPswe cells. Moreover, the amelioration ability of this compound against the in vivo memory impairment was further evaluated by APP-PS1 double transgenic mice model. It is discovered that treatment of 9 mg/kg/day of TDC could obviously decrease Abeta production and Abeta plaque formation, while efficiently improve the memory impairment based on Morris water maze test. Our findings thus demonstrated that the natural product TDC as a new BACE1 inhibitor could ameliorate memory impairment in mice, and is expected to be potentially used as a lead compound for further anti-AD reagent development.
Full Text Available Aim: The aim of this study was to identify mild cognitive deficits in Parkinson's disease (PD prior to extensive neurodegeneration and to evaluate the extent to which dopamine depletion and other disease-related predictors can explain cognitive profiles. Methods: Neuropsychological performances of 40 nondemented early-stage PD patients and 42 healthy controls were compared across on or off dopaminergic medications. Stepwise regression evaluated cognitive predictors of early-stage PD and disease-related predictors of PD cognition (levodopa dose, disease duration, Unified Parkinson's Disease Rating Scale score, sleep, quality of life, and mood across on and off states. Results: Neuropsychological performance was lower in PD patients across cognitive domains with significant memory, naming, visuomotor, and complex attention/executive deficits, but with intact visuospatial, simple attention, and phonemic fluency functions. However, medication effects were absent except for simple attention. Regression analyses revealed age, working memory, and memory recall to be the best cognitive predictors of PD, while age, quality of life, disease duration, and anxiety predicted PD cognition in the off state. Conclusion: Nondemented early-stage PD patients presented with extensive mild cognitive deficits including prominent memory impairment. The profile was inconsistent with expected isolated frontostriatal dysfunction previously attributed to dopamine depletion and this highlights the need to further characterize extranigral sources of mild cognitive impairment in PD.
Frydecka, Dorota; Beszłej, Jan Aleksander; Gościmski, Piotr; Kiejna, Andrzej; Misiak, Błażej
The aim of this study was to compare cognitive performance between schizophrenia patients with and without treatment resistance (TRS and non-TRS patients) taking into account psychopathological symptoms and antipsychotic treatment. The following cognitive tests were administered to 53 TRS patients and 32 non-TRS subjects: Rey Auditory Verbal Learning Test (RAVLT), Trail Making Tests (TMT-A and TMT-B), verbal fluency tests (FAS test and Supermarket), as well as selected Wechsler Adults Intelligence Scale (WAIS-R-PI) subtests: Digit Symbol Coding Test, Digit Span Forward and Backward and Similarities. TRS patients performed significantly worse in comparison with non-TRS patients on the measures of processing speed (TMT-A, Stroop test, FAS test, Supermarket test, Digit Symbol Coding test), verbal fluency (FAS test, Supermarket test), cognitive flexibility and executive functions (Stroop test) after controlling for age, illness duration, clinical symptoms severity, the number of years of completed education and antipsychotics' dose. Cognitive performance was associated with negative and general symptomatology. Anticholinergic activity of antipsychotics had debilitating effect on cognitive functioning in non-TRS patients (FAS test) and in TRS patients (TMT-B test, Stroop test, RAVLT subtests, Digit Coding test and Similarities test), while low anticholinergic activity of antipsychotics was associated with better cognitive performance in non-TRS patients (Backward Digit Span test) and in TRS patients (Similarities test). Results of this study indicate that cognitive deficits are more robust in TRS patients than in non-TRS subjects, and are associated with clinical symptoms as well as the treatment with antipsychotics that exert high anticholinergic activity.
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.
Beata Joanna Kasperek-Zimowska
Full Text Available A growing number of publications indicates presence of significant deficits in social cognition in patients with anorexia nervosa (AN. These deficits appear to be comparable in qualitative and quantitative dimension with impairment of the same functions among people with Asperger syndrome (AS. The aim of this study is to identify subject areas in the field of impairment of social cognition processes among people with Asperger syndrome and anorexia nervosa taking into consideration the potential contribution of genetic pathways of oxytocin and vasopressin in the pathogenesis of these diseases. In the first part of the paper a systematic analysis of studies aimed at the evaluation of the processes of social cognition among patients with AN and AS has been carried out. The results of a significant number of studies confirm the presence of deficits in social cognition in AN and AS. In addition, among patients with AN and AS there exists a similar structure and distribution of the brain functions in regions responsible for social cognition. The second part of the paper describes the role of the oxytocin-vasopressin system (OT-AVP in the processes of social cognition in AN and AS. Its genetic basis and the possible importance of single nucleotide polymorphisms within the genes: OXT, AVP, CD38, OXTR, AVPR1A and LNPEP have also been presented.
Kasperek-Zimowska, Beata Joanna; Zimowski, Janusz Grzegorz; Biernacka, Katarzyna; Kucharska-Pietura, Katarzyna; Rybakowski, Filip
A growing number of publications indicates presence of significant deficits in social cognition in patients with anorexia nervosa (AN). These deficits appear to be comparable in qualitative and quantitative dimension with impairment of the same functions among people with Asperger syndrome (AS). The aim of this study is to identify subject areas in the field of impairment of social cognition processes among people with Asperger syndrome and anorexia nervosa taking into consideration the potential contribution of genetic pathways of oxytocin and vasopressin in the pathogenesis of these diseases. In the first part of the paper a systematic analysis of studies aimed at the evaluation of the processes of social cognition among patients with AN and AS has been carried out. The results of a significant number of studies confirm the presence of deficits in social cognition in AN and AS. In addition, among patients with AN and AS there exists a similar structure and distribution of the brain functions in regions responsible for social cognition. The second part of the paper describes the role of the oxytocin-vasopressin system (OT-AVP) in the processes of social cognition in AN and AS. Its genetic basis and the possible importance of single nucleotide polymorphisms within the genes: OXT, AVP, CD38, OXTR, AVPR1A and LNPEP have also been presented.
Full Text Available Parkinson’s disease (PD is known to cause neuropsychiatric symptoms (NPS. It has been established that the more advanced the motor stage of PD is, the more frequent and severe the NPS may be. However, the relationship between NPS and stage of cognitive decline is less well understood. This is important because the majority of people with PD will experience some degree of cognitive decline during the course of their disease, and there is a high risk of developing dementia (PDD. In non-PD populations there is a strong association between NPS and cognitive impairment and the same association may apply in PD. Consequently, the aim of this article is to provide a brief overview of NPS in PD from the perspective of stage of cognitive decline. We highlight studies that have demonstrated the increasing prevalence and severity of NPS with increasing cognitive impairment in PD. We point out the importance of apathy as a possible precursor to PDD. We also describe the negative impact of NPS and cognitive impairment on caregiver distress and quality of life. Finally, we have summarised findings from key studies of cognitive enhancers in PDD which have examined the effect of these treatments on NPS.
Full Text Available Abstract Background Cognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors involving in cognitive decline for the countries where the older population is growing rapidly. The aim of this study was to examine the association between socio-demographic and health-related factors and cognitive impairment in the elderly in Taiwan. Methods We analysed data from 2119 persons aged 65 years and over who participated in the 2005 National Health Interview Survey. Cognitive impairment was defined as having the score of the Mini Mental State Examination lower than 24. The χ2 test and multiple logistic regression models were used to evaluate the association between cognitive impairment and variables of socio-demography, chronic diseases, geriatric conditions, lifestyle, and dietary factors. Results The prevalence of cognitive impairment was 22.2%. Results of multivariate analysis indicated that low education, being single, low social support, lower lipid level, history of stroke, physical inactivity, non-coffee drinking and poor physical function were associated with a higher risk of cognitive impairment. Conclusion Most of the characteristics in relation to cognitive impairment identified in our analysis are potentially modifiable. These results suggest that improving lifestyle behaviours such as regular exercise and increased social participation could help prevent or decrease the risk of cognitive impairment. Further investigations using longitudinal data are needed to clarify our findings.
Full Text Available Introduction The number of patents with dementia increases among hip fracture patients. Cognitive dysfunction is defined as a premorbid state which is potentionally negatively related to short-term functional outcome. Objective To assess the relationship between cognitive status on admission and functional gain during an early rehabilitation period in elderly hip fracture patients. Methods Forty-five elderly patients with surgically treated hip fracture were examined. Cognitive status was assessed by the Mini Mental State Examination (MMSE at admission; functional status was assessed by the motor subscale of Functional Independence Measure (FIM at admission and before discharge, while absolute functional gain was determined by the motor FIM gain (FIM discharge - FIM admission. Absolute functional gain was analyzed in respect to cognitive status. Results Both cognitively impaired and cognitively intact hip fracture patients exhibited overall FIM motor improvements, as well as functional gains in specific FIM motor areas (p<0.01. Absolute functional gain, however, was higher in 1 cognitively intact compared to cognitively impaired patients (p<0.01, and 2 cognitively moderately impaired patients compared to severely cognitively impaired patients (p<0.01. No difference in functional gain was detected between the patients with moderately cognitively impaired compared to the cognitive intact patients (p>0.05. Conclusion The systematic use of MMSE identifies cognitively impaired hip fracture patients, and effectively predicts their short-term functional outcome. A higher admission cognitive status is related to a more favorable short term rehabilitation outcome. In spite of cognitive impairment, elderly patients with hip fracture can benefit from participation in rehabilitation programmes. The systematic identification of cognitively impaired hip fracture patients at admission facilitates optimal treatment and rehabilitation, and thus enables the best
Svenningsson, Per; Westman, Eric; Ballard, Clive; Aarsland, Dag
Dementia is one of the most common and important aspects of Parkinson's disease and has consequences for patients and caregivers, and has health-related costs. Mild cognitive impairment is also common and frequently progresses to dementia. The underlying mechanisms of dementia associated with Parkinson's disease are only partly known and no mechanism-based treatments are available. Both dysmetabolism of α-synuclein and amyloid-protein and cholinergic deficits contribute to cognitive impairment in Parkinson's disease, and preliminary findings show that imaging and neurophysiological and peripheral biomarkers could be useful in diagnosis and prognosis. Rivastigmine is the only licensed treatment for dementia in Parkinson's disease, but emerging evidence suggests that memantine might also be useful. Whether these or other treatments can delay the progression from mild cognitive impairment to dementia in Parkinson's disease is a key research question.
Ni, Cheng; Li, Zhengqian; Qian, Min; Zhou, Yang; Wang, Jun; Guo, Xiangyang, E-mail: firstname.lastname@example.org
Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.
Gongvatana, Assawin; Schweinsburg, Brian C; Taylor, Michael J; Theilmann, Rebecca J; Letendre, Scott L; Alhassoon, Omar M; Jacobus, Joanna; Woods, Steven P; Jernigan, Terry L; Ellis, Ronald J; Frank, Lawrence R; Grant, Igor
Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.
Full Text Available Abstract Background Hearing impairment is a prevalent and chronic condition in older people. This study investigated the relationship between cognitive function and hearing impairment in a Japanese population. Methods A pure-tone average (0.5-2.0 kHz was used to evaluate hearing impairment in 846 participants of the Iwaki Health Promotion Project who were aged at least 50 years old (310 men and 536 women. We also administered the Mini-Mental State Examination (MMSE, the Center for Epidemiologic Studies for Depression (CES-D scale, Starkstein's apathy scale (AS and the Short Form Health Survey Version 2 (SF-36v2. A multiple linear regression analysis assessed the association between hearing impairment and mental correlates. Results The overall prevalence of hearing impairment in this study population was 37.7%. The participants with hearing impairment were older and less educated compared to those with no hearing problems. We observed significant differences in the MMSE and AS scores between the mild/moderate to severe groups versus the non-impaired group. After adjusting for age, gender and amount of education, hearing impairment was significantly associated with MMSE and AS scores, but not with CES-D scores. Hearing impairment was significantly related to the social functioning (SF and role emotional (RE scores of the SF-36v2. Conclusions Hearing impairment is common among older people and is associated with cognitive impairment, apathy and a poor health-related quality of life. Screening for and correcting hearing impairments might improve the quality of life and functional status of older patients.
Metzger, Florian G.; Hobert, Markus A.; Ehlis, Ann-Christine; Hasmann, Sandra E.; Hahn, Tim; Eschweiler, Gerhard W.; Berg, Daniela; Fallgatter, Andreas J.; Maetzler, Walter
Differentiation of mild cognitive impairment from depression in elderly adults is a clinically relevant issue which is not sufficiently solved. Gait and dual task (DT) parameters may have the potential to complement current diagnostic work-up, as both dementia and depression are associated with changes of gait and DT parameters. Methods: Seven hundred and four participants of the TREND study (Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration) aged 50–80 years were assessed using the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery for testing cognition and Beck's Depression Inventory for evaluation of depression. Based on these results, four groups were defined: acute depressed (N = 53), cognitively mildly impaired (N = 97), acute depressed, and cognitively mildly impaired (N = 15), and controls (N = 536). Participants underwent a 20 m walk and checking boxes task under single (ST) and DT conditions. ST and DT performance and dual task costs (DTC) were calculated. Due to the typical age of increasing incidence of depressive and also cognitive symptoms, the 7th decade was calculated separately. Results: ST speeds of gait and checking boxes, DT walking speed, and walking DTC were significantly different between groups. Healthy controls were the fastest in all paradigms and cognitively mildly impaired had higher DTC than depressed individuals. Additionally, we constructed a multivariate predictive model differentiating the groups on a single-subject level. Conclusion: DT parameters are simply and comfortably measureable, and DTC can easily be determined. The combination of these parameters allows a differentiation of depressed and cognitively mildly impaired elderly adults.
The purpose of this study was to look at the interface between stressful life events, gender, cognitive impairment, and the use of outpatient physician services among older adults. A theoretical rationale is presented, suggesting that older men who are suffering from either mild or moderate levels of cognitive impairment are especially likely to use outpatient physician services when they are confronted by undesirable stressful events. Analyses with data provided by a nationwide sample of elderly people provide support for this complex three-way interaction.
Laws, Keith R; Irvine, Karen; Gale, Tim M
Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer's disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.
Cosentino, Stephanie; Schupf, Nicole; Christensen, Kaare;
IMPORTANCE Family studies of centenarians and long-lived persons have found substantial familial aggregation of survival to extreme ages; however, the extent to which such familial longevity is characterized by cognitively intact survival is not established. OBJECTIVE To determine whether familie...
Objective To explore the relationship between cerebrovascular steno-occlusive disease and neuropsychological performance by cognitive function assessment. Methods Using a case-control study,45 patients with cerebrovascular steno-occlusive lesions (patient group) and 59 control subjects without cerebrovascular
Vascular disease plays an important role in the development of dementia, also in patients diagnosed with Alzheimer’s disease. Risk factors such as hypertension, obesity, and type 2 diabetes, are associated with a two-fold increased risk of cognitive dysfunction and dementia. The development of cogni
Full Text Available External degradations in incoming speech reduce understanding, and hearing impairment further compounds the problem. While cognitive mechanisms alleviate some of the difficulties, their effectiveness may change with age. In our research, reviewed here, we investigated cognitive compensation with hearing impairment, cochlear implants, and aging, via (a phonemic restoration as a measure of top-down filling of missing speech, (b listening effort and response times as a measure of increased cognitive processing, and (c visual world paradigm and eye gazing as a measure of the use of context and its time course. Our results indicate that between speech degradations and their cognitive compensation, there is a fine balance that seems to vary greatly across individuals. Hearing impairment or inadequate hearing device settings may limit compensation benefits. Cochlear implants seem to allow the effective use of sentential context, but likely at the cost of delayed processing. Linguistic and lexical knowledge, which play an important role in compensation, may be successfully employed in advanced age, as some compensatory mechanisms seem to be preserved. These findings indicate that cognitive compensation in hearing impairment can be highly complicated—not always absent, but also not easily predicted by speech intelligibility tests only.
Clarke, Jeanne; Pals, Carina; Benard, Michel R.; Bhargava, Pranesh; Saija, Jefta; Sarampalis, Anastasios; Wagner, Anita; Gaudrain, Etienne
External degradations in incoming speech reduce understanding, and hearing impairment further compounds the problem. While cognitive mechanisms alleviate some of the difficulties, their effectiveness may change with age. In our research, reviewed here, we investigated cognitive compensation with hearing impairment, cochlear implants, and aging, via (a) phonemic restoration as a measure of top-down filling of missing speech, (b) listening effort and response times as a measure of increased cognitive processing, and (c) visual world paradigm and eye gazing as a measure of the use of context and its time course. Our results indicate that between speech degradations and their cognitive compensation, there is a fine balance that seems to vary greatly across individuals. Hearing impairment or inadequate hearing device settings may limit compensation benefits. Cochlear implants seem to allow the effective use of sentential context, but likely at the cost of delayed processing. Linguistic and lexical knowledge, which play an important role in compensation, may be successfully employed in advanced age, as some compensatory mechanisms seem to be preserved. These findings indicate that cognitive compensation in hearing impairment can be highly complicated—not always absent, but also not easily predicted by speech intelligibility tests only.
Cusi, Andrée M; Macqueen, Glenda M; McKinnon, Margaret C
The literature concerning social cognitive performance in people with bipolar disorder (BD) reveals a mixed pattern of findings. We compared performance between patients with BD and matched controls on two social cognitive tasks that involved: (i) the decoding of mental states from pictures of eyes (Reading the Mind in the Eyes Test), and (ii) a video-based test that requires participants to discriminate social cues to make interpersonal judgments (Interpersonal Perception Task-15; IPT-15). We also sought to evaluate the association between symptom severity, social functioning, and social cognitive ability in patients with BD. Relative to controls, patients with BD were impaired at discriminating mental states from pictures of eyes and in making complex social judgments. Impaired responding on the IPT-15 was also associated with reduced psychosocial functioning. These results provide evidence of impaired performance on complex tests of social cognition in patients with BD. Impairments in social cognition may be associated with well-documented declines in the frequency of social interactions and development of interpersonal relationships found in this patient population.
Vinther-Jensen, Tua; Larsen, Ida U.; Hjermind, Lena E.; Budtz-Jørgensen, Esben; Nielsen, Troels T.; Nørremølle, Anne; Jørgen E. Nielsen; Vogel, Asmus
Background Involuntary movements, neuropsychiatric symptoms, and cognitive impairment are all part of the symptom triad in Huntington’s disease (HD). Despite the fact that neuropsychiatric symptoms and cognitive decline may be early manifestations of HD, the clinical diagnosis is conventionally based on the presence of involuntary movements and a positive genetic test for the HD CAG repeat expansion. After investigating the frequencies of the triad manifestations in a large outpatient clinica...
Campos, Lidiane S.; Guimarães, Rachel P.; Piovesana, Luiza G.; Azevedo,Paula C. de; Leonilda M B Santos; Anelyssa D’Abreu
Objective To estimate the clinical and demographics aspects that may contribute to cognitive impairment and psychiatric symptoms in Parkinson’s disease (PD). Method All patients answered a structured standardized clinical questionnaire. Two movement disorders specialists performed the following scale: Unified Parkinson’s disease rating score (UPDRS), the modified Hoehn and Yahr staging, Schwab and England Scale, SCOPA cognition (SCOPA-COG), SCOPA-Psychiatric complications (SCOPA-PC) and Non-M...
Lee, Hyun Joon; Kang, Ji Seung; Kim, Yeong In
Background and purpose Cerebral white matter (WM) lesions are frequently observed in human cerebrovascular diseases, and are believed to be responsible for cognitive impairment. Various neuroprotective agents can suppress this type of WM or neuronal damage. In this study, we investigated whether citicoline, a drug used to treat acute ischemic stroke, can attenuate WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. Methods Animals were divided into immediate- and dela...
Wang, Zigao; Xiong, Lu; Wan, Wenbin; Duan, Lijie; Bai, Xiaojing; Zu, Hengbing
Alzheimer’s disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis. PMID:28228716
Tarantini, Stefano; Hertelendy, Peter; Tucsek, Zsuzsanna; Valcarcel-Ares, M Noa; Smith, Nataliya; Menyhart, Akos; Farkas, Eszter; Hodges, Erik L; Towner, Rheal; Deak, Ferenc; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan; Toth, Peter
There is increasing evidence that vascular risk factors, including aging, hypertension, diabetes mellitus, and obesity, promote cognitive impairment; however, the underlying mechanisms remain obscure. Cerebral blood flow (CBF) is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism is known to be impaired in the aforementioned pathophysiologic conditions. To establish a direct relationship between impaired NVC and cognitive decline, we induced neurovascular uncoupling pharmacologically in mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH), the NO synthase inhibitor l-NG-Nitroarginine methyl ester (L-NAME), and the COX inhibitor indomethacin decreased NVC by over 60% mimicking the aging phenotype, which was associated with significantly impaired spatial working memory (Y-maze), recognition memory (Novel object recognition), and impairment in motor coordination (Rotarod). Blood pressure (tail cuff) and basal cerebral perfusion (arterial spin labeling perfusion MRI) were unaffected. Thus, selective experimental disruption of NVC is associated with significant impairment of cognitive and sensorimotor function, recapitulating neurologic symptoms and signs observed in brain aging and pathophysiologic conditions associated with accelerated cerebromicrovascular aging.
Rabin, Laura A; Chi, Susan Y; Wang, Cuiling; Fogel, Joshua; Kann, Sarah J; Aronov, Avner
Despite the relevance of prospective memory to everyday functioning and the ability to live independently, prospective memory tasks are rarely incorporated into clinical evaluations of older adults. We investigated the validity and clinical utility of a recently developed measure, the Royal Prince Alfred Prospective Memory Test (RPA-ProMem), in a demographically diverse, non-demented, community-dwelling sample of 257 older adults (mean age = 80.78 years, 67.7% female) with amnestic mild cognitive impairment (aMCI, n = 18), nonamestic mild cognitive impairment (naMCI, n = 38), subjective cognitive decline (SCD, n = 83) despite intact performance on traditional episodic memory tests, and healthy controls (HC, n = 118). Those with aMCI and naMCI performed significantly worse than controls on the RPA-ProMem and its subtasks (time-based, event-based, short-term, long-term). Also, those with SCD scored significantly lower than controls on long-term, more naturalistic subtasks. Additional results supported the validity and inter-rater reliability of the RPA-ProMem and demonstrated a relation between test scores and informant reports of real-world functioning. The RPA-ProMem may help detect subtle cognitive changes manifested by individuals in the earliest stages of dementia, which may be difficult to capture with traditional episodic memory tests. Also, assessment of prospective memory can help guide the development of cognitive interventions for older adults at risk for dementia.
Gold, David A
Basic activities of daily living (ADL) are self-maintenance abilities such as dressing or bathing. Instrumental ADL (IADL) are more complex everyday tasks, such as preparing a meal or managing finances (Lawton & Brody, 1969). IADL questionnaires play an important role in assessing the functional abilities of older adults and evaluating the impact of cognitive impairment on routine activities. This paper examined the cognitive processes that underlie IADL performance and concluded that the accurate and reliable execution of IADL likely draws upon the integrity of a wide range of cognitive processes. This review examined IADL in mild cognitive impairment (MCI) because of the controversial nature of distinguishing a significant decline in functional abilities in those with MCI versus dementia or MCI versus cognitively normal aging. The challenges of investigating IADL empirically were explored, as well as some of the reasons for the inconsistent findings in the literature. A review of questionnaire-based assessments of IADL indicated that: MCI can be distinguished statistically from healthy older adults and dementia, individuals with multiple domain MCI are more impaired on IADL than those with single domain MCI, mild IADL changes can be predictive of future cognitive decline, and the ability to manage finances may be among the earliest IADL changes in MCI and a strong predictor of conversion to dementia. This paper concluded with recommendations for more sensitive and reliable IADL questionnaires.
Michael L. Alosco
Full Text Available Background: Cerebral hypoperfusion accompanies heart failure (HF and is associated with reduced cognitive performance. Obesity is prevalent in persons with HF and is also a likely contributor to cognitive function, as it has been independently linked to cognitive impairment in healthy individuals. The current study examined the association between obesity and cognitive performance among older adults with HF and whether obesity interacts with cerebral hypoperfusion to exacerbate cognitive impairment. Methods: Patients with HF (n = 99, 67.46 ± 11.36 years of age completed neuropsychological testing and impedance cardiography. Cerebral blood flow velocity (CBF-V measured by transcranial Doppler sonography quantified cerebral perfusion and body mass index (BMI operationalized obesity. Results: A hierarchical regression analysis showed that lower CBF-V was associated with reduced performance on tests of attention/executive function and memory. Elevated BMI was independently associated with reduced attention/executive function and language test performance. Notably, a significant interaction between CBF-V and BMI indicated that a combination of hypoperfusion and high BMI has an especially adverse influence on attention/executive function in HF patients. Conclusions: The current findings suggest that cerebral hypoperfusion and obesity interact to impair cognitive performance in persons with HF. These results may have important clinical implications, as HF patients who are at high risk for cerebral hypoperfusion may benefit from weight reduction.
Orestes V. Forlenza
Full Text Available Objective: To critically review and evaluate existing knowledge on the conceptual limits and clinical usefulness of the diagnosis of mild cognitive impairment (MCI and the neuropsychological assessment and short- and long-term prognosis thereof. Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012. Based on the search terms mild cognitive impairment or MCI and epidemiology or diagnosis, we retrieved 1,698 articles, of which 248 were critically eligible (cross-sectional and longitudinal studies; the abstracts of the remaining 1,450 articles were also reviewed. Results: A critical review on the MCI construct is provided, including conceptual and diagnostic aspects; epidemiological relevance; clinical assessment; prognosis; and outcome. The distinct definitions of cognitive impairment, MCI included, yield clinically heterogeneous groups of individuals. Those who will eventually progress to dementia may present with symptoms consistent with the definition of MCI; conversely, individuals with MCI may remain stable or return to normal cognitive function. Conclusion: On clinical grounds, the cross-sectional diagnosis of MCI has limited prognostic relevance. The characterization of persistent and/or progressive cognitive deficits over time is a better approach for identification of cases at the pre-dementia stages, particularly if these cognitive abnormalities are consistent with the natural history of incipient Alzheimer's disease.
Full Text Available Cognitive reserve is the ability to optimize performance through differential recruitment of brain networks, which may reflect the use of alternative cognitive strategies. Work is one of the most important sources of cognitive stimulation during adulthood. Mild cognitive impairment (MCI represents an intermediate status between normal aging and dementia. As a consequence, this is considered a risk group regarding cognition. In order to study the probable association between occupational complexity and cognitive performance in a group of patients with MCI, a non-probabilistic intentional sample was dispensed on a group of 80 patients. Occupational complexity was explored by the Questionnaire on Agency of Labor Activity (CAAL, according to its acronym in Spanish and a set of neuropsychological tests, which assessed cognitive performance in different areas: memory, attention, language and executive function, were administered. Results reveal that occupational complexity is associated to cognitive performance of elderly adults with MCI. With respect to working with Data, an increase in neuropsychological tests that demand high levels of attention and imply processing speed and working memory can be noted. Regarding the complexity of working with People, an association between the level of occupational complexity and an increase in verbal abilities and verbal reasoning can be seen. On the other hand, working with Things could be associated with better performance in specific areas of cognition such as visuospatial abilities. These results add up as empirical evidence to the fields of cognitive neurology and gerontology and to the cognitive reserve hypothesis, showing how complex environments can enhance cognition in old age. It adds evidence that help to understand which psychological, social and labor factors intervene in the cognitive reserve of an elder adult in cognitive risk.
Full Text Available Peng Yin,1,* Qingfeng Ma,2,* Limin Wang,1 Peng Lin,3 Mei Zhang,1 Shige Qi,1 Zhihui Wang1 1National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 2Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 3Department of Health Education, Qingdao Municipal Center for Disease Control and Prevention, Qingdao, People’s Republic of China *These authors contributed equally to this work Background: Previous studies suggested an association between chronic obstructive pulmonary disease (COPD and cognitive impairment, mostly in developed countries. There is no evidence available on the association between these two common chronic disorders in the elderly people in People’s Republic of China where the population is aging rapidly.Methods: The study population was randomly selected from a nationally representative Disease Surveillance Point System in People’s Republic of China. A standardized questionnaire was administered by trained interviewers during a face-to-face interview in the field survey conducted in 2010–2011. Cognitive function was assessed using the Mini-Mental State Examination. COPD was measured by self-report and the Medical Research Council respiratory questionnaire was used to assess respiratory symptoms. A multivariate logistic regression model was applied to examine the association between COPD and cognitive impairment with adjustment for potential confounding factors.Results: A total of 16,629 subjects aged over 60 years were included in the study. The prevalence of cognitive impairment was 9.4% (95% confidence interval [CI] 7.7, 11.1. Chronic phlegm was associated with significantly higher prevalence of cognitive impairment in models adjusted for age, sex, marital status, geographic region, urban/rural, education, smoking status, alcohol drinking, and indoor air pollution (odds ratio [OR] 1.46, 95% CI 1.11, 1.93. Chronic
Hyun Cho; Jee-Hyun Kwon; Sun-Young Kim
BACKGROUND: Many studies have suggested that one possible etiology of mild cognitive impairment is small vessel cerebrovascular disease, which is associated with small subcortical infarcts and white matter abnormalities. These white matter changes have been detected as white matter hyperintensity (WMH) using magnetic resonance imaging. WMH may be associated with frontal lobe dysfunction. OBJECTIVE: To examine white matter changes in mild cognitive impairment patients of different subtypes, and to evaluate the correlation between white matter changes and neuropsychological characteristics, demographic information, vascular risk factors, and mild cognitive impairment subtypes. DESIGN, TIME AND SETTING: The neurophysiological, comparison study was performed at the Department of Neurology Memory Clinic, Ulsan University Hospital, South Korea, between March 2007 and March 2008.PARTICIPANTS: Out of a total of 83 subjects with clinically diagnosed mild cognitive impairment at the out-patient clinic, 3 subjects with severe WMH were excluded. A total of 80 subjects were included in this study. No patients suffered from cognitive impairment induced by neurological diseases, mental disorders, or somatic diseases. In accordance with magnetic resonance imaging results, the patients were assigned to two subtypes: 56 subjects without WMH and 24 subjects with WMH. METHODS: All patients were subjected to a standard neuropsychological battery using the Korean version of the Mini-Mental State Examination, Clinical Dementia Rating, and comprehensive Seoul Neuropsychological Screening Battery. The Clinical Dementia Rating reflected general cognitive function of patients. Results from the Seoul Neuropsychological Screening Battery reflected attention, language function, visuospatial function, verbal memory, nonverbal memory, long-term memory, and frontal/executive function. Magnetic resonance imaging was used to map changes in the brain. MAIN OUTCOME MEASURES: The association between
Natalie C. Palavra
Full Text Available Mild Cognitive Impairment in Parkinson’s Disease (PD-MCI is common and may be associated with accelerated progression to dementia. Considering the importance of this emerging entity, new diagnostic criteria have recently been proposed. Early recognition and accurate classification of PD-MCI could offer opportunities for novel therapeutic interventions. This review discusses current definitions for PD-MCI, the screening tools used, the pattern of cognitive deficits observed, and the predictors of cognitive decline and transition to Parkinson’s Disease Dementia. Emerging biomarkers, which may aid diagnosis, are also explored and the role of novel treatment options is considered.
Gavrilova, S I; Fedorova, Ia B; Gantman; Kalyn, Ia B; Kolykhalov, I V
The objective was to study efficacy and safety of ceraxon (citicoline) used perorally in dose 1000 mg daily in the treatment of cognitive disturbances in patients with amnesic type of mild cognitive impairment (MCI). Twenty patients, aged from 50 to 90 years, received ceraxon in dose 1000 mg twice a day during 90 days. The state of patients was assessed with a battery of scales and tests with the following statistical data analysis. The significant results on the clinical effect of the drug on cognitive disturbances and good tolerability of ceraxon have been obtained. The authors recommend ceraxon for long-term preventive treatment in high risk populations for Alzheimer's disease.
González-Redondo, Rafael; García-García, David; Clavero, Pedro; Gasca-Salas, Carmen; García-Eulate, Reyes; Zubieta, José L; Arbizu, Javier; Obeso, José A; Rodríguez-Oroz, María C
The pathophysiological process underlying cognitive decline in Parkinson's disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson's disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson's disease, we examined 46 patients with Parkinson's disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. (18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging scans were obtained, co-registered, corrected for partial volume effect and spatially normalized to the Montreal Neurological Institute space in each subject. Smoothing was applied to the positron emission tomography and magnetic resonance imaging scans to equalize their effective smoothness and resolution (10 mm and 12 mm full-width at half-maximum and Gaussian kernel, respectively). Z-score maps for atrophy and for hypometabolism were obtained by comparing individual images to the data set of control subjects. For each group of patients, a paired Student's t-test was performed to statistically compare the two Z-map modalities (P mild cognitive impairment, hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In patients with dementia, the hypometabolic areas observed in the group with mild cognitive impairment were replaced by areas of atrophy, which were surrounded by extensive zones of hypometabolism. Areas where atrophy was more
Reuser, Mieke; Willekens, Frans J; Bonneux, Luc
Improved health may extend or shorten the duration of cognitive impairment by postponing incidence or death. We assess the duration of cognitive impairment in the US Health and Retirement Study (1992-2004) by self reported BMI, smoking and levels of education in men and women and three ethnic groups. We define multistate life tables by the transition rates to cognitive impairment, recovery and death and estimate Cox proportional hazard ratios for the studied determinants. 95% confidence intervals are obtained by bootstrapping. 55 year old white men and women expect to live 25.4 and 30.0 years, of which 1.7 [95% confidence intervals 1.5; 1.9] years and 2.7 [2.4; 2.9] years with cognitive impairment. Both black men and women live 3.7 [2.9; 4.5] years longer with cognitive impairment than whites, Hispanic men and women 3.2 [1.9; 4.6] and 5.8 [4.2; 7.5] years. BMI makes no difference. Smoking decreases the duration of cognitive impairment with 0.8 [0.4; 1.3] years by high mortality. Highly educated men and women live longer, but 1.6 years [1.1; 2.2] and 1.9 years [1.6; 2.6] shorter with cognitive impairment than lowly educated men and women. The effect of education is more pronounced among ethnic minorities. Higher life expectancy goes together with a longer period of cognitive impairment, but not for higher levels of education: that extends life in good cognitive health but shortens the period of cognitive impairment. The increased duration of cognitive impairment in minority ethnic groups needs further study, also in Europe.
Ávila-Villanueva, Marina; Rebollo-Vázquez, Ana; Ruiz-Sánchez de León, José M; Valentí, Meritxell; Medina, Miguel; Fernández-Blázquez, Miguel A
Introduction: Subjective memory complaints (SMC) in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI) by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ). Materials and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI). The EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis (EFA) and Item Response Theory (IRT) were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI. Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely Forgetfulness of Immediate Information (FII), Executive Functions (EF) and Prospective Memory (PM) proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10). Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to use the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints.
Ávila-Villanueva, Marina; Rebollo-Vázquez, Ana; Ruiz-Sánchez de León, José M.; Valentí, Meritxell; Medina, Miguel; Fernández-Blázquez, Miguel A.
Introduction: Subjective memory complaints (SMC) in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI) by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ). Materials and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI). The EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis (EFA) and Item Response Theory (IRT) were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI. Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely Forgetfulness of Immediate Information (FII), Executive Functions (EF) and Prospective Memory (PM) proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10). Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to use the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints. PMID:27757082
Erleben, Lene Lillemark; Sørensen, Lauge; Mysling, Peter
This work investigates a novel way of looking at the regions in the brain and their relationship as possible markers to classify normal control (NC), mild cognitive impaired (MCI), and Alzheimer Disease (AD) subjects. MRI scans from a subset of 101 subjects from the ADNI study at baseline was used...
Kuzhuppilly Ramakrishnan, Nisha; Marosi, Krisztina; Nyakas, Csaba J.; Kwizera, Chantal; Elsinga, Philip H.; Ishiwata, Kiichi; Luiten, Paul G M; Dierckx, Rudi A. J. O.; van Waarde, Aren
PURPOSE: Sigma-1 receptors are involved in learning and memory processes. We assessed sigma-1 receptor expression and memory function in two animal models of cognitive impairment. PROCEDURES: Male Wistar-Hannover rats were either lesioned by unilateral injection of N-methyl-D-aspartic acid in the nu
Harvey, Judy; Hux, Karen; Snell, Jeffry
This single case study served to examine text-to-speech (TTS) effects on reading rate and comprehension in an individual with mild aphasia and cognitive impairment. Findings showed faster reading, given TTS presented at a normal speaking rate, but no significant comprehension changes. TTS may support reading in people with aphasia when time…
Jekel, K.; Damian, M.; Wattmo, C.; Hausner, L.; Bullock, R.; Connelly, P.J.; Dubois, B.; Eriksdotter, M.; Ewers, M.; Graessel, E.; Kramberger, M.G.; Law, E.; Mecocci, P.; Molinuevo, J.L.; Nygard, L.; Olde Rikkert, M.G.M.; Orgogozo, J.M.; Pasquier, F.; Peres, K.; Salmon, E.; Sikkes, S.A.; Sobow, T.; Spiegel, R.; Tsolaki, M.; Winblad, B.; Frolich, L.
INTRODUCTION: There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic r
Bradshaw, William; Roseborough, David
This study evaluated the effectiveness of cognitive-behavioral interventions in the treatment of persons with schizophrenia who experienced significant residual symptoms and impaired functioning despite their adherence to medication. The study used an aggregated AB single-system research design across 22 participants to evaluate change in clinical…
Gao, F; Barker, P B
MR spectroscopy is a noninvasive technique that allows the detection of several naturally occurring compounds (metabolites) from well-defined regions of interest within the human brain. Alzheimer disease, a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. During the past 20 years, multiple studies have been performed on MR spectroscopy in patients with both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy studies have found decreased N-acetylaspartate and increased myo-inositol in both patients with mild cognitive impairment and Alzheimer disease, with greater changes in Alzheimer disease than in mild cognitive impairment. This review summarizes the information content of proton brain MR spectroscopy and its related technical aspects, as well as applications of MR spectroscopy to mild cognitive impairment and Alzheimer disease. While MR spectroscopy may have some value in the differential diagnosis of dementias and assessing prognosis, more likely its role in the near future will be predominantly as a tool for monitoring disease response or progression in treatment trials. More work is needed to evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its relationship to other imaging modalities.
Marton, Klara; Abramoff, Brocha; Rosenzweig, Shari
This investigation examined the relationship between social pragmatics, soci