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Background: Cognitive impairment due to multiple sclerosis (MS) is common and often limits occupational functioning, contributes to disability, and reduces quality of life. Early detection of cognitive involvement in MS is critical for treatment planning and intervention, and frequent, regular cognitive monitoring may provide insight into subtle changes in disease progression., Objective: To compare the sensitivity and specificity of clinical, computer-based and experimental measures to early cognitive involvement in MS., Methods: Cognitive functioning was compared in MS participants early in the disease course to matched healthy controls using conventional, computer-based and functional assessments: the Brief International Cognitive Assessment in MS (BICAMS); the computer-based Cogstate Brief Battery (CBB); the Attention Network Test-Interaction (ANT-I), including intra-individual variability; and the Test of Everyday Cognitive Ability (TECA), a functional measure of instrumental activities of daily living., Results: MS participants (n = 25, mean disease duration= 5.82 ± 3.65 years) and demographically matched healthy controls (n = 29) completed the cognitive assessments. The Cogstate measure of choice reaction time (AUC = 0.73, p = .004), intra-individual variability on the ANT-I (AUC = 0.79, p = .001), and TECA (AUC = 0.78, p = .001) scores were the most sensitive and specific markers of cognitive involvement in MS., Conclusions: Brief, repeatable, computer-based measures of reaction time and variability detect early MS associated cognitive involvement., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aim: Guidelines recommend routine assessment and management of mood and cognition after stroke, but little is known about the value or feasibility of providing neuropsychology input during the hyper-acute period. We aimed to identify and describe the extent and nature of neuropsychological needs and to investigate the feasibility of providing direct neuropsychology input within a hyper-acute setting., Methods: Over a 7-month period, Multidisciplinary Team (MDT) members of a central London Hyper-Acute Stroke Unit (HASU) identified stroke patients who they believed would benefit from neuropsychology input, and categorised the nature of neuropsychology intervention required. We examined the demographic and clinical characteristics of the patients identified and the type of intervention required., Results: 23% of patients (101/448) were identified as requiring neuropsychology input. Patients deemed to require input were younger, more likely to be male and more functionally disabled than those not requiring input. Cognitive assessment was the main identified need (93%) followed by mood (29%) and family support (9%). 30% of patients required two types of intervention. During a pilot of neuropsychology provision, 17 patients were seen; 15 completed a full cognitive assessment. All patients assessed presented with cognitive impairment despite three being deemed cognitively intact (> standardised cut-off) using a cognitive screening tool., Conclusion: We showed that direct neuropsychology input on a HASU is necessary for complex and varied interventions involving cognition, mood and family support. Furthermore, input is feasible and useful in detecting cognitive impairment not revealed by screening instruments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The abbreviated Minimal Assessment of Cognitive Function in Multiple Sclerosis (aMACFIMS) was designed using four shortened measures from the MACFIMS. Semantic fluency was suggested as an alternative task; however, its equivalency as part of this battery has yet to be examined., Objectives: 1) To determine the optimal semantic fluency raw score cut-offs; 2) compare the modified aMACFIMS (with semantic fluency) to the standard aMACFIMS (with phonemic fluency); and 3) compare the expanded aMACFIMS (with both verbal fluency measures) to the Brief International Cognitive Assessment in MS (BICAMS)., Methods: Receiver-operating-characteristic curves were used to identify the optimal cut-off at -1.5 and - 2.0 standard deviation (SD) impairment criteria (n = 335). The diagnostic accuracies were compared between the different versions of the aMACFIMS and BICAMS (n = 146)., Results: The raw score cut-offs for semantic fluency (13 and 11 words) had high sensitivity (100%) and specificity (96.6% - 98.6%). The modified aMACFIMS did not significantly differ from the standard aMACFIMS. The expanded aMACFIMS had stronger specificity (84.8%) and positive predictive value (85.9%) than the BICAMS., Conclusions: Semantic fluency can be used as an alternative, though including both measures results in the most effective aMACFIMS version. Using semantic fluency may be especially valuable when evaluating older PwMS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The Montreal Cognitive Assessment (MoCA) is a popular cognitive screening tool used in stroke, but lacks sensitivity for detecting impairment in stroke-relevant domains of processing speed, non-verbal memory and executive functions. Our aim was to assess whether the test accuracy of the MoCA can be improved with additional tailored screening items targeting these three domains., Methods: We included 196 patients admitted to an acute stroke unit at the National Hospital for Neurology and Neurosurgery, Queen Square (QS), London. Participants completed the MoCA as well as a series of additional QS-screening items designed to assess speed of processing, non-verbal memory and executive functions. Performance on the MoCA and QS screening items was compared with performance on "gold standard" neuropsychological assessment., Results: In our sample, 22% of patients were classified as "cognitively intact" on the traditional MoCA alone (≥ 25). However, when tested on the QS-screening items, 40% of these patients failed on speed of processing, 56% failed on non-verbal memory and 26% failed on executive functions. Compared with neuropsychological assessment, the QS-screening items had good sensitivity (QS-Speed: 0.85; QS-Vis: 0.71; QS-EF: 0.73) and modest specificity (QS-Speed: 0.59; QS-Vis: 0.39; QS-EF: 0.54), regardless of stroke lateralisation., Conclusion: Additional screening items detected impairments in speed of processing, non-verbal memory and executive functions over and above those captured using the standard MoCA. The use of these QS-screening items improves the detection of post-stroke cognitive deficits in domains not adequately covered by the standard MoCA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Limbic encephalitis (LE) is an autoimmune condition characterized by amnestic syndrome, psychiatric features and seizures. Early diagnosis and prompt treatment are crucial to avoid long-term sequelae, including psycho-cognitive deficits and persisting seizures. The aim of our study was to analyze the characteristics of 33 LE patients in order to identify possible prognostic factors associated with the development of chronic epilepsy., Methods: This is a retrospective cohort study including adult patients diagnosed with LE in the period 2010-2017 and followed up for ≥12 months. Demographics, seizure semiology, EEG pattern, MRI features, CSF/serum findings were reviewed., Results: All 33 LE patients (19 M/14F, mean age 61.2 years) presented seizures. Thirty subjects had memory deficits; 22 presented behavioural/mood disorders. Serum and/or CSF auto-antibodies were detected in 12 patients. In 31 subjects brain MRI at onset showed typical alterations involving temporal lobes. All patients received immunotherapy. At follow-up, 13/33 had developed chronic epilepsy; predisposing factors included delay in diagnosis (p = .009), low seizure frequency at onset (p = .02), absence of amnestic syndrome (p = .02) and absence/rarity of inter-ictal epileptic discharges on EEG (p = .06)., Conclusions: LE with paucisymptomatic electro-clinical presentation seemed to be associated to chronic epilepsy more than LE presenting with definite and severe "limbic syndrome"., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Despite the prevalence of dual-task (e.g., walking while talking) deficits in people with multiple sclerosis (MS), no neuroimaging studies to date have examined neuronal networks used for dual-task processing or specific brain areas related to dual-task performance in this population. A better understanding of the relationship among underlying brain areas and dual-task performance may improve targeted rehabilitation programs. The objective of this study was to examine relationships between neuroimaging measures and clinical measures of dual-task performance, and reported falls in persons with MS., Materials and Methods: All participants completed measures of dual-task performance, a fall history, and neuroimaging on a 3 T MRI scanner. Spearman correlations were used to examine relationships among dual-task performance, falls and neuroimaging measures., Results: Eighteen females with relapsing-remitting MS [mean age = 45.5 ± 8.2 SD; mean symptom duration = 12.3 ± 6.7 years; Expanded Disability Status Scale median 2.25 (range 1.5-4)] participated in this study. Structural imaging measures of supplementary motor area (SMA) interhemispheric connectivity were significantly related to dual-task walking variability., Conclusions: The SMA interhemispheric tract may play a role in dual-task performance. Structural neuroimaging may be a useful adjunct to clinical measures to predict performance and provide information about recovery patterns in MS. Functional recovery can be challenging to objectively report in MS; diffusion tensor imaging could show microstructural improvements and suggest improved connectivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Patients with complete occlusion of the internal carotid artery (CAO) are vulnerable to cerebral hypoperfusion. Since cerebral hypoperfusion is associated with accelerated cognitive decline, patients with CAO may have an increased risk of cognitive impairment. We aimed to assess the prevalence and profile of cognitive impairment in patients with CAO and to explore the relation between hemodynamic impairment and cognitive functioning., Methods: We systematically searched Medline and EMBASE for studies including patients with symptomatic or asymptomatic CAO subjected to cognitive testing that were published between 1980 and 2017. We did not include patients with carotid stenosis. We obtained data on type of study, patient characteristics, cerebral imaging and neuropsychological testing. In addition, we extracted data on potential causes of systemic hemodynamic impairment and the presence and stage of cerebral hemodynamic impairment. We assessed methodological quality of included studies with the Newcastle-Ottawa Scale., Results: We found eight studies comprising 244 patients (mean age 61 years, 76% male, 93% symptomatic CAO). The proportion of patients with cognitive impairment ranged from 54 to 71% in four studies; in the other four studies patients with CAO performed worse on cognitive testing than controls, but results were not quantified. Impairment was reported in all cognitive domains. We found no data on the association between systemic hemodynamic impairment and cognitive functioning. Studies that assessed whether cerebral hemodynamic impairment was associated with cognitive functioning showed conflicting results., Conclusion: In patients with CAO, cognitive impairment is present in about half to two-thirds of patients and is not restricted to specific cognitive domains. The effect of systemic and cerebral hemodynamic impairment on cognitive functioning in patients with CAO deserves further study., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke which carries a high case-fatality rate. Those who survive the ictus of aneurysm rupture harbor substantial risks of neurological morbidity, functional disability, and cognitive dysfunction. Although the pervasiveness of cognitive impairment is widely acknowledged as a long-term sequela of aSAH, the mechanisms underlying its development are poorly understood. The onset of aSAH elicits activation of the inflammatory cascade, and ongoing neuroinflammation is suspected to contribute to secondary complications, such as vasospasm and delayed cerebral ischemia. In this review, we analyze the extant literature regarding the relationship between neuroinflammation and cognitive dysfunction after aSAH. Pro-inflammatory cytokines appear to play a role in maintaining normal cognitive function in adults unaffected by aSAH. However, in the setting of aSAH, elevated cytokine levels may correlate with worse neuropsychological outcomes. This seemingly dichotomous relationship between neuroinflammation and cognition suggests that the action of cytokines varies, depending on their physiologic environment. Experimental therapies which suppress the immune response to aSAH appear to have a beneficial effect on cognitive outcomes. However, further studies are necessary to determine the utility of inflammatory mediators as biomarkers of neurocognitive outcomes, as well as their role in the management of aSAH., (Copyright © 2018. Published by Elsevier B.V.)

Background: Cognitive impairment is a prevalent and often intrusive problem among persons with multiple sclerosis (PwMS). Valid and reliable assessments, including quick screening measures, are crucial. The Brief International Cognitive Assessment for MS (BICAMS) was developed for this reason. While it lends itself to use in locations where formal neuropsychological resources might be limited, it does not include measures of verbal fluency or executive functioning, domains assessed as part of the Minimal Assessment of Cognitive Function in MS (MACFIMS)., Objective: Given previous evidence that shortened MACFIMS measures have strong criterion validity, this study aimed to determine which of these should be included in the abbreviated MACFIMS (aMACFIMS), and how the aMACFIMS compares to the BICAMS., Methods: One hundred forty-seven PwMS were included in the analyses. A stepwise logistic regression was used to determine the measures in the aMACFIMS. Receiver-operating-characteristic (ROC) curves assessed the classification accuracy, sensitivity, and specificity. The batteries' sensitivity, specificity, and predictive values were then compared., Results: Compared to the BICAMS, the final aMACFIMS had higher specificity (87% versus 72%) and positive predictive value (86% versus 77%), but lower sensitivity (71% versus 81%)., Conclusion: The aMACFIMS has several benefits, including reduced administration time and the addition of a verbal fluency/executive functioning measure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Tele-rehabilitation after stroke holds promise for under-resourced settings, especially sub-Saharan Africa (SSA), with its immense stroke burden and severely limited physical therapy services., Objective: To preliminarily assess the feasibility and outcomes of mobile technology-assisted physical therapy exercises for stroke survivors in Ghana., Methods: We conducted a prospective, single arm, pre-post study involving 20 stroke survivors recruited from a tertiary medical center, who received a Smartphone with the 9zest Stroke App® to deliver individualized, goal-targeted 5-days-a-week exercise program that was remotely supervised by a tele-therapist for 12 weeks. Outcome measures included changes in stroke levity scale scores (SLS), Modified Rankin score (MRS), Montreal Cognitive Assessment (MOCA), and feasibility indicators., Results: Among study participants, mean ± SD age was 54.6 ± 10.2 years, 11 (55%) were men, average time from stroke onset was 6 months. No participants dropped out. Compared with baseline status, mean ± SD scores on SLS improved from 7.5 ± 3.1 to 11.8 ± 2.2 at month 1 (p < 0.0001) and 12.2 ± 2.4 at month 3 (p < 0.0001), MOCA scores improved from 18.2 ± 4.3 to 20.4 ± 4.7 at month 1 (p = 0.14), and 22.2 ± 7.6 at month 3 (p = 0.047). Mean ± SD weekly sessions performed by participants per month was 5.7 ± 5.8 and duration of sessions was 25.5 ± 16.2 min. Erratic internet connectivity negatively affected full compliance with the intervention, although satisfaction ratings by study participants were excellent., Conclusion: It is feasible to administer an m-health delivered physical therapy intervention in SSA, with high user satisfaction. Randomized trials to assess the efficacy and cost-effectiveness of this intervention are warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well-known that excessive deposition of Aβ in the brain is a crucial part of the pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has attracted much attention. Impairment of the blood-brain barrier (BBB) leads to abnormal amyloid-β (Aβ) transport, and chronic cerebral hypoperfusion causes Aβ deposition throughout the onset and progression of AD. Endothelial progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our previous studies have shown that a reduced number of EPCs in the peripheral blood results in cerebral vascular repair disorder, cerebral hypoperfusion and neurodegeneration, which might be related to the cognitive dysfunction of AD patients. This study was designed to confirm whether EPCs transplantation could repair the blood-brain barrier, stimulate angiogenesis and reduce Aβ deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent with previous studies, EPC transplants also increased the microvessel density. We observed that Aβ senile plaque deposition was decreased and hippocampal cell apoptosis was reduced after EPCs transplantation. The Morris water maze test showed that spatial learning and memory functions were significantly improved in mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression of tight junction proteins, repair BBB tight junction function, stimulate angiogenesis, promote Aβ clearance, and decrease neuronal loss, ultimately improve cognitive function. Taken together, these data demonstrate EPCs may play an important role in the therapeutic implications for vascular dysfunction in AD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Several correlations between cognitive impairment (CI), radiologic markers and cognitive reserve (CR) have been documented in MS., Obiective: To evaluate correlation between CI and brain volume (BV) considering CR as possibile mitigating factor., Methods: 195 relapsing MS patients underwent a neuropsychological assessment using BICAMS. BV was estimated using SIENAX to obtain normalized volume of brain (NBV), white matter (NWV), gray matter (NGV) and cortical gray matter (CGV). CR was estimated using a previously validated tool., Results: Pearson test showed a correlation between the symbol digit modality test (SDMT) score and NBV (r=0.38; p<0.000) NGV(r=0.31; p<0.000), CGV (r=0.35; p<0.000) and CRI score(r=0.42; p<0.000). Linear regression (dependent variable:SDMT) showed a relationship with CR scores (p=0.000) and NGV(p<0.000). A difference was detected between cognitive impaired and preserved patients regarding mean of NBV(p=0.002), NGV(p=0.007), CGV(p=0.002) and CR Scores (p=0.007). Anova showed a association between the presence of CI (dependent variable) and the interaction term CRIQ × CGV (p=0.004) whit adjustment for age and disability evaluated by EDSS., Conclusions: Our study shows a correlation between cognition and BV, in particular gray matter volume. Cognitive reserve is also confirmed as an important element playing a role in the complex interaction to determine the cognitive functions in MS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cerebellar and cognitive dysfunction can occur early in clinically isolated syndrome (CIS). Eye tracking is a reliable tool for the evaluation of both subtle cerebellar symptoms and cognitive impairment., Objectives: To investigate the early cognitive profile using neuropsychological and ocular motor (OM) testing in CIS with and without cerebellar dysfunction with OM testing compared to healthy subjects (HS)., Methods: Twenty-eight patients and 12 HC underwent OM and neuropsychological testing. Cerebellar impairment was defined by the registration of saccadic intrusions and/or at least 10% of dysmetria during ocular motor recording. Visually guided saccade (VGS), memory-guided saccade (MGS) and antisaccade (AS) paradigms were compared to neuropsychological assessments., Results: The group of patients with cerebellar dysfunction (n=16) performed worse on MGS latencies and error rates, and had worse working memory, executive function and information processing speed (IPS) z scores than patients without cerebellar dysfunction. IPS was correlated with the AS error rate in all patients and with the VGS error rate and the MGS final eye position ratio in cerebellar patients., Conclusion: Eye tracking is a sensitive tool to assess cognitive and cerebellar dysfunctions in CIS. In CIS patients, cerebellar impairment is associated with working memory, executive functions and IPS slowness., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To explore the prevalence and clinical correlates of executive impairment and behavioral changes, and the determinants of health-related quality of life (HRQoL) in Chinese patients with progressive supranuclear palsy (PSP)., Methods: This cross-sectional study included 52 patients with PSP. The frontal assessment battery (FAB) was used to assess executive function, while the frontal behavioral inventory (FBI) and Neuropsychiatry Inventory (NPI) were used to assess behavioral changes. The HRQoL of PSP patients was assessed using the Parkinson's disease questionnaire-39 (PDQ-39). The stepwise multiple regression model was use to explore their related factors., Results: Executive deficits were detected in forty patients (76.9%), and fifty patients (96.2%) displayed varied degrees of frontal behavioral changes. FAB score was associated with Montreal Cognitive Assessment score (β=0.620, P<0.001) and Unified Parkinson's disease Rating Scale (UPDRS) III score (β=-0.238, P=0.025). FBI score was associated with FAB score (β=-0.311, P=0.005) and UPDRS III score (β=0.251, P=0.018). PDQ-39 score was associated with FAB score (β=-0.324, P=0.005), UPDRS III score (β=0.306, P=0.008), and Hamilton Depression Rating Scale score (β=0.353, P=0.001)., Conclusions: Executive deficits and behavioral changes are common in Chinese PSP patients. Executive functions are associated with disease severity. Patients with executive dysfunction and more severe disease disability are likely to exhibit frontal behavioral abnormalities. Executive dysfunction, disease severity and depression exert an impact on the HRQoL of PSP patients., (Copyright © 2017. Published by Elsevier B.V.)

Background: Medical decision-making capacity (MDC) refers to the ability to make informed decisions about treatment and declines in cognition are associated with declines in MDC across multiple disease entities. However, although it is well known that cognitive impairment is prevalent in multiple sclerosis (MS), little is known about MDC in the disease., Methods: Data from 22 persons with progressive MS and 18 healthy controls were analyzed. All diagnoses were made by a board-certified neurologist with experience in MS. All study participants were administered a vignette-based measure of MDC and also a neuropsychological battery., Results: Performance on three MDC consent standards (i.e., Appreciation, Reasoning, Understanding) was significantly lower for people with progressive MS as compared to healthy controls. In the progressive MS group, verbal fluency was the primary cognitive predictor for both Reasoning and Understanding consent standards. Verbal learning and memory was the primary cognitive predictor for Appreciation. MS severity was not significantly correlated with any MDC variable., Conclusion: MDC is a complex and cognitively mediated functional ability that is impaired in many people with progressive MS. Verbal measures of fluency and memory are strongly associated with MDC performances in the current sample of people with MS and could potentially be utilized to quickly screen for MDC impairment in MS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The extent to which individuals with ET who have clinically significant cognitive impairment are aware of their cognitive changes is unclear. Reduced awareness has important implications for everyday function and decision-making., Methods: 150 individuals with ET (109 Normal Cognition (ET-NC group), and 30 with MCI and 11 dementia (ET-CI group)) completed self-ratings and objective assessments of memory, language, and executive functioning. Discrepancy scores were calculated to assess awareness of cognitive functioning. One sample t-tests evaluated whether mean discrepancy scores in each group were comparable to zero (i.e., accurate). Analyses of covariance (ANCOVA) compared discrepancy scores across two groups controlling for age and education., Results: In the ET-NC group, discrepancy scores for language (M=-0.08, SD=1.10) and executive functioning (M=-0.01, SD=0.99) were comparable to zero. Memory discrepancy scores (M=0.32, SD=1.22) were greater than zero. In the ET-CI group, memory, (M=0.78, SD=1.01), language, (M=0.46, SD=0.95), and executive (M=0.39, SD=1.14) discrepancy scores were all greater than zero. Discrepancy scores were larger in ET-CI group than in ET-NC group for memory: F(1,148)=4.02, p=0.047, language: F(1,148)=6.16, p=0.014, and executive: F(1,148)=4.51, p=0.035., Conclusions: Individuals with ET and normal cognition accurately assessed their language and executive abilities, demonstrating mild overconfidence in memory function. Individuals with ET and cognitive impairment overestimated their performance in all domains of functioning. Since ET is linked to increased risk for cognitive impairment, and such impairment may not be accurately perceived, cognitive functioning should be proactively and regularly screened in ET., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Olfactory dysfunction represents a frequent and disturbing non-motor manifestation of Parkinson's disease (PD). The pathophysiology of olfactory dysfunction in PD is still poorly understood. Experimental evidence suggests that olfactory impairment could be related to central cholinergic dysfunction. Short latency afferent inhibition (SAI) technique gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with different degrees of olfactory dysfunction. We applied SAI technique in 31 patients with PD. These patients also underwent Olfactory Event-Related Potentials (OERPs) studies to objectively evaluate the olfactory system and a battery of neuropsychological tests to assess the cognitive functions. Absent OERPs indicated a severe olfactory dysfunction in 13 subjects. The presence of OERPs with an alteration in latency and/or amplitude can be considered as a borderline condition of slight alteration of smell and was found in other 15 patients. Only 3 patients showed normal OERPs. SAI was significantly reduced in the PD patients with absent OERPs compared with those with present but abnormal OERPs. Neuropsychological examination showed a mild cognitive impairment in 12 out of 13 PD patients with severe olfactory dysfunction, and in 3 out of the 15 patients with borderline olfactory dysfunction. SAI abnormalities and presence of severe olfactory impairment strongly support the hypothesis of cholinergic dysfunction in some patients with PD, who will probably develop a dementia. Longitudinal studies are required to verify whether SAI abnormalities in PD patients with olfactory dysfunction can predict a future severe cognitive decline., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The main goal of this study was to investigate the presence of cognitive impairment in patients infected with HTLV-1 presenting or not TSP/HAM., Methods: Cross-sectional study including 104 participants: 37 asymptomatic HTLV-1 carriers, 37 patients diagnosed with TSP/HAM and 30 HTLV-1 negative control patients. Within the HTLV-1 positive group, 53 were female and 21 were male, the average age was 46 (SD=13.5) and the average schooling time was 7.7years (SD=3.3).The sociodemographic variables (genre, age and education) were compared between the three groups. The assessment tools used were: Beck Depression Inventory, Lawton's Activities of Daily Life Scale and a complete neuropsychological battery. The application of these assessment tools was carried out in blind. Both HTLV-1 asymptomatic subjects and HAM/TSP patients showed a lower performance on neuropsychological tests and higher depression scores when compared to the control group. HTLV-1 patients performed poorly in several cognitive domains, but only fluid intelligence, estimated intellectual functioning, immediate and delayed recall of visual memory and information processing speed (in the specific case of patients with TSP/HAM) reached statistical significance when compared with controls. Depression was not associated with cognitive impairment. HTLV-1 carriers presented a higher frequency of cognitive impairment than normal controls., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of diabetes mellitus (DM) on cognitive performance and longitudinal volumetric brain changes in a cohort of cognitively normal mild PD patients., Methods: Prospective study of idiopathic PD subjects who underwent baseline and follow-up MRI imaging and neuropsychological assessments at 6month intervals for 3years. Subjects were classified based on the presence (PD-DM) or absence of DM (PD-No DM) at baseline. Volumetric analysis was performed using FreeSurfer 5.3 image analysis suite. Brain volume and cognition were compared and analyzed cross-sectionally and longitudinally. Analyses were corrected for intracranial volume., Results: There were 65 PD-no DM and 12 PD-DM subjects at baseline with comparable global cognition at baseline. PD-DM subjects had lower cortical grey matter (GM), amygdala, frontal white matter and temporal white matter volumes and higher total white matter hyperintensity and periventricular hyperintensities. After mean follow-up of 29.08months, there were 51 PD-no DM and 11 PD-DM subjects. PD-DM subjects demonstrated greater decline in MMSE and MOCA scores compared to PD-No DM. PD-DM subjects had a higher rate of atrophy in the cortical WM, particularly in the parietal and occipital white matter., Conclusion: Mild PD patients with DM have lower GM and WM volumes at baseline and higher WMH volumes, despite comparable cognitive scores. Longitudinally, DM in PD results in greater rate of cognitive decline, associated with higher WM atrophy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson's disease (PD) severity and cognitive impairment., Methods: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7m, turn 180° and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson's Disease (SCOPA-Cog), revised Addenbrooke's Cognitive Index (ACE-R) and Barratt's Impulsivity Scale 11 (BIS-11)., Results: Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p<0.001) and PDQ-39 scores (p<0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times., Conclusions: Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Affective disorders and personality changes have long been considered pre-motor aspects of Parkinson's disease (PD). Many authors have used the term "premorbid personality" to define distinctive features of PD patients' personality characterized by reduced exploration of new environmental stimuli or potential reward sources ("novelty seeking") and avoidance behaviour ("harm avoidance") present before motor features. The functional correlates underlying the personality changes described in PD, implicate dysfunction of meso-cortico-limbic and striatal circuits. As disease progresses, the imbalance of neurotransmitter systems secondary to degenerative processes, along with dopamine replacement therapy, can produce a reversal of behaviours and an increase in reward seeking, laying the foundations for the emergence of the impulse control disorders. Personality disorders can be interpreted, therefore, as the result of individual susceptibility arising from intrinsic degenerative processes and individual personality features, in combination with extrinsic factors such as lifestyle, PD motor dysfunction and drug treatment. For a better understanding of personality disorders observed in PD and their relationship with the prodromal stage of the disease, prospective clinical studies are needed that correlate different personality profiles with other disease progression markers. Here, we review previous studies investigating the clinical, cognitive and behavioural correlates of personality traits in PD patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Herbal medicines have been recently employed in research and clinical studies for the potential treatment of behavioral and psychological symptoms associated with Alzheimer's Disease (AD) and other types of dementia. The present study investigates the effect of trans-crocetin, an active constituent of Crocus sativus L., to restore in vitro the reduced ability of AD patients' monocytes to degrade amyloid-β (1-42) (Aβ 42 ). CD14 + monocytes from 22 sporadic AD patients with moderate cognitive impairment were isolated; then, the role of trans-crocetin, purified from saffron extracts, was evaluated in terms of Aβ 42 degradation rate through flow cytometry, as well as expression of cathepsin B by Western blotting. We observed that low micromolar doses of trans-crocetin enhanced Aβ 42 degradation in AD monocytes through the upregulation of the lysosomal protease cathepsin B. CA074Me, a potent and selective cathepsin B inhibitor, counteracted such trans-crocetin-induced effect. These data suggest that the carotenoid trans-crocetin improves in vitro the clearance of Aβ 42 through the involvement of cathepsin B, and this could be of value in developing a new anti-amyloid strategy in AD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The missense mutation V717I in amyloid precursor protein (APP) gene has been reported in many early-onset familial Alzheimer's disease (EOFAD) families. However, no detailed clinical picture regarding this mutation has ever been described for Chinese EOFAD. We investigate the age at onset (AAO), initial clinical features and non-cognitive neurological symptoms in 34 affected subjects from five Han Chinese EOFAD families with the APPV717I mutation to characterize the clinical phenotype. The AAO was 54.7±4.9years (n=34), with the APOE ɛ4 allele correlating with a decreased AAO. Prominent early affective symptoms, executive dysfunction and disorientation at onset were exhibited in 26 (76.5%), 18 (52.9%) and 16 (47%) cases, respectively. Spastic paraparesis and cerebellar ataxia occurred frequently in 13 (38.2%) and 12 (35.3%) cases, respectively, during the late stages of disease. The specific clinical phenotype of the APPV717I mutation for Chinese families is characterized by prominent early affective symptoms, executive dysfunction and disorientation as well as frequent late spastic paraparesis and cerebellar ataxia as compared to Western reports. We conclude that ethnic differences, environment or additional unknown factors may challenge the homogeneity of EOFAD with identical APP mutations., (Copyright © 2016. Published by Elsevier B.V.)

Background: We investigated the prevalence of parkinsonism in frontotemporal dementia (FTD) subtypes and the cognitive and behavioral differences between FTD with and without parkinsonism in a well-structured, prospective cohort., Methods: One hundred and ninety-one FTD patients were enrolled and all patients underwent comprehensive neurological evaluations, neuropsychological tests, and the Unified Parkinson's Disease Rating Scale., Results: The prevalence of parkinsonism was 38.7% (74 patients), and included 33 (46.5%) behavioral variant FTD (bvFTD), 16 (24.2%) semantic dementia (SD), 19 (45.2%) progressive nonfluent aphasia (PNFA), and 6 (50%) FTD associated with motor neuron disease (FTD-MND). SD patients with parkinsonism had higher CDR sum of boxes scores (9.7±4.5 vs 6.2±4.5, p=0.024), frontal behavioral inventory total score (33.7±20.5 vs 24.3±14.5, p=0.045), and executive function score of frontal executive dysfunction, disinhibition, and apathy (28.9±13.7 vs 19.2±12.9, p=0.021) than those without parkinsonism. Seoul Instrumental Activities of Daily Living score (bvFTD: 23.5±11.7 vs 17.3±11.3, p=0.031, SD: 23.1±11.1 vs 11.3±9.3, p=0.005) was higher for bvFTD and SD with parkinsonism than for those without parkinsonism., Conclusions: Parkinsonism is found to be more common in patients with bvFTD, PNFA, and FTD-MND patients than those with SD. Behavioral disturbances were more prominent in SD with parkinsonism than without. Additional studies are needed to determine the pathomechanism and optimal treatment of parkinsonism in different FTD subtypes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To investigate the cortical metabolic alterations that precedes longitudinal cognitive decline in Parkinson's disease (PD)., Methods: We analyzed the data of 46 PD patients who did not have dementia at baseline and completed 3-year follow-up. Based on the results of general cognitive, memory and visuospatial tests, patients were classified into cognitively normal PD (PD-CogNL), PD with mild cognitive impairment (PD-MCI), and PD dementia (PDD). The regional cerebral glucose metabolism at rest was measured using 18 F-fluorodeoxyglucose positron emission tomography. Voxel-wise effect size analyses were performed to delineate abnormal metabolic patterns associated with changes in cognitive status in PD., Results: At baseline, 29 patients had PD-CogNL, and 17 patients had PD-MCI. At follow-up, 28 patients had PD-CogNL, 12 patients had PD-MCI, and 6 patients developed PDD. Seventeen of 29 PD-CogNL patients remained to be PD-CogNL, and 9 PD-CogNL patients converted to PD-MCI. Eleven PD-MCI patients reverted to normal cognition during follow-up. 3 PD-CogNL and 3 PD-MCI patients developed PDD. Cognitively stable PD-CogNL group had frontal predominant hypometabolism. PDD converters showed parieto-occipital hypometabolism at baseline regardless of whether a patient's initial cognitive status is PD-CogNL or PD-MCI., Conclusions: Parieto-occipital hypometabolism is a good predictor of early dementia conversion in PD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Purpose: Major cognitive disorder (MND) following vascular events is known as second causes of dementia after Alzheimer's disease (AD). Acute onset MND due to isolated hippocampal infarction has not been recognized as a specific subtype of vascular dementia, and there is no validated criteria for the identification of such cases, either clinically or radiologically., Results: Among 7200 patients with first-ever ischemic stroke, 22 patients (0.3%) showed acute isolated ischemic lesions in the hippocampus. Four of them presented acute MND characterized by confusion at the beginning of stroke and thereafter they developed typical clinical characteristics of MND. These cases allowed us to delineate a specific type of dementia characterized by confusion at stroke onset, dull and aimless appearance, verbal and visual immediate or delayed memory deficits, dysexecutive syndrome. Major cognitive disorder was developed due to anterior involvement of the hippocampus with little interindividual variation. Stroke mechanism was artery-to-artery embolism or cardioembolism which can explain isolated infarcts of the hippocampus., Conclusions: Hippocampal MND generally occurred in acute bilateral isolated hippocampal infarcts. The clinical characteristic of MND may be secondary to lesions of the body of the hippocampus and interruption of the hippocampo-temporal pathways and cortical projections., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: To determine the effects of Type 2 diabetes (DM2) on levels of brain amyloidosis and cognition in a community-dwelling cohort of nondemented elderly individuals., Methods: 33 subjects (16 DM2, 17 nondiabetic) were prospectively recruited. Subjects underwent a PET scan using the amyloid tracer, Pittsburgh Compound B, and a neuropsychological evaluation. Associations between DM2, brain amyloidosis, and cognition were assessed using multivariate regressions, adjusting for age and APOE4 status., Results: DM2 subjects had lower global cognitive function (p=0.018), as measured by the Repeatable Battery for the Assessment of Neuropsychological Status. There was no difference in brain amyloidosis between groups (p=0.25)., Conclusions: Community-dwelling, nondemented individuals with DM2 had greater cognitive deficits, which do not appear to be mediated by brain amyloidosis. Further studies exploring potential mediators of these cognitive deficits should be performed., Competing Interests: The authors have reported no conflicts of interest., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias., Methods: Cognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions., Results: The COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women., Conclusions: Our results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication., (Copyright © 2016. Published by Elsevier B.V.)

Objects: We designed this study to extensively compare the neuropsychological profiles of Alzheimer's disease (AD) and mixed dementia (MD) in a large multicenter cohort of patients. Specifically, we performed subgroup analyses to examine group differences associated with dementia severity., Methods: A total of 1021 AD patients and 577 MD patients were included from the Clinical Research Center for Dementia of South Korea (CREDOS) Study. All patients underwent comprehensive neuropsychological and functional ratings, as well as complete physical and neurological examinations. To avoid floor confounds, only patients with Clinical Dementia Rating (CDR) scores of 0.5-2.0 were included., Results: Overall, MD patients showed worse performance in frontal/executive function than those with AD. Stratification by dementia severity revealed a significant difference in global cognitive function scores between AD and MD patients only in the low severity groups (CDR 0.5). Also, MD patients showed worse performance in frontal/executive function domains in the CDR 0.5 groups whereas they had better performance in the memory domain in the CDR 1 groups than did AD patients. Additionally, AD patients showed better performance than MD patients with respect to activities of daily living at CDR levels 0.5 and 1. All differences had disappeared at the CDR 2 level of global dementia severity., Conclusion: This study suggests that there are significant differences in neuropsychological profiles between AD and MD patients, with the pattern of this difference varying distinctively according to dementia severity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aim: We compared the behavioral and psychological symptoms of Alzheimer's disease (AD) and Parkinson's disease (PD) in order to determine the characteristic features of each disorder., Methods: For this retrospective cohort study, we compared the behavioral and psychological symptoms of 288AD patients and 189 PD patients (mean age, 74.6±5.9 and 73.0±8.7years respectively). Symptoms were evaluated using the geriatric depression scale (GDS), apathy scale (AS), and Abe's behavioral and psychological symptoms of dementia score (ABS)., Results: AD patients had higher AS and ABS scores than PD patients. A gender-dependent comparison showed that ABS scores were worse in female AD patients than in female PD patients (p=0.001). A subscale analysis of ABS scores revealed that male AD patients were only significantly different from male PD patients in 1 item, whereas female AD patients were significantly different from female PD patients in 4 items. Among patients with mild cognitive decline, no differences in affective scores were observed. Alternatively, among patients with moderate cognitive decline, affective scores on all 3 scales were worse in PD patients than in AD patients., Conclusions: The present age- and gender-matched retrospective analysis identified greater behavioral and psychological disease severity in female AD patients relative to female PD patients, and greater affective severity in PD patients versus AD patients with a similar degree of cognitive decline., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aims: We investigated cognitive abnormalities using standard tests in Chinese patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with those in normal controls., Methods: Twenty-three patients with iRBD and 23 normal controls were included in this study. All of the participants underwent one night of video-polysomnography (PSG) monitoring to certify REM sleep without atonia or abnormal behaviors. The cognitive assessments were administered and scored according to a standard procedure, including global cognitive screening and attention/processing speed, executive function, memory, language, and visuospatial ability testing., Results: Patients with iRBD had similar scores of the Mini Mental State Examination (MMSE) but lower Montreal Cognitive Assessment (MoCA) scores compared with controls (p>0.05, p=0.013). The iRBD patients performed poorly on verbal memory tests, which included immediate recall (p<0.001), delayed recall (p<0.001), and false recognitions (p=0.002) of the Rey Auditory Verbal Learning Test (RAVLT). The visual memory and visuospatial abilities were also impaired in iRBD patients, as reflected by the copy (p=0.005) and immediate (p=0.004) and delayed (p=0.003) recall of the Rey-Osterrieth complex figure, although no difference was found after Bonferroni correction. The duration of RBD was 6.98±8.10years. After controlling for age, the duration of RBD was only correlated with the Trail Making Test B (r=0.613, p=0.045) and block design (r=-0.667, p=0.025)., Conclusions: Impaired verbal memory was observed in iRBD patients who identified as Chinese. MoCA could detect cognitive abnormalities and serve as a screening scale. The present study further confirmed cognitive deficits in iRBD as an early clinical marker in the prodromal stage of synucleinopathy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Sumoylation regulates transcription factor transactivation, protein-protein interactions, and appropriate subcellular localization of certain proteins. Previous studies have shown that sumoylation of amyloid precursor protein (APP) is associated with decreased levels of amyloid beta (Aβ) proteins, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between polymorphisms of the SUMO genes and the risk of AD. Our study subjects consisted of 144 AD patients and 335 healthy controls without dementia. We focused on tagged single nucleotide polymorphisms (tagSNPs) of the SUMO1 and SUMO2 genes. The tagSNPs were amplified by PCR and sequenced. We used binary logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the associations between SUMO gene polymorphisms and the risk of AD. We found that rs12472035 polymorphism of SUMO1 was significantly associated with an increased risk of AD in male group (the CT genotype of rs12472035: adjusted OR=8.737, 95% CI=2.041-37.41, p-value=0.003). In addition, two polymorphisms of SUMO2 were significantly associated with an increased risk of AD in female group (the GA genotype of rs35271045: adjusted OR=2.879, 95% CI=1.399-5.924, p-value=0.004; and the TC genotype of rs9913676: adjusted OR=2.460, 95% CI=1.197-5.057, p-value=0.014). Furthermore, three combinations were associated with an increased risk of AD. Our data suggest that three individual polymorphisms and three combinations may be potential risk factors for AD in Korean population., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Subjective reports of sleep disturbance are a common feature of Huntington's disease (HD); however, there is limited research investigating the relationship between sleep problems with changes in brain and behaviour. This study aimed to investigate whether subjective reports of sleep problems in HD are associated with brain volume, neurocognitive decline, and neuropsychiatric symptoms. This retrospective pilot study used brain volume, neurocognitive and neuropsychiatric data from premanifest (pre-HD) and symptomatic HD (symp-HD). Subjective sleep problem was measured using the sleep item of the Beck's Depression Inventory-II (BDI-II). Pre-HD individuals reporting sleep problems had significantly poorer neuropsychiatric outcomes compared to those not reporting sleep problems. In the symp-HD group, those with sleep problems had significantly accelerated thalamic degeneration and poorer neuropsychiatric outcomes compared to those without sleep problems. There was no relationship between subjective sleep problems and neurocognitive measures. These findings suggest an association between subjective sleep disturbance, neuropathology, and development of neuropsychiatric symptoms in HD. Further studies using quantitative EEG-based monitoring of sleep in HD and changes in the brain and behaviour will be necessary to establish the causal nature of this relationship., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Impaired renal function and proteinuria have been associated with cognitive impairment and dementia. Chronic kidney disease is considered to be an independent risk factor for Lewy body spectrum disorders (LBD). However, few studies have mentioned an association between proteinuria and cognition in LBD. We investigated the relationship between proteinuria and cognitive dysfunction in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB)., Methods: Among 186 patients with LBD, 53 had PD-normal cognition (PD-NC), 76 had PD-mild cognitive impairment (PD-MCI), 43 had PD-dementia (PDD) and 14 had DLB. The urine protein/creatinine ratio was calculated using the spot urine test and brain magnetic resonance scans was obtained in all patients., Results: The urine protein/creatinine ratio was significantly higher in patients with PDD and DLB than in those with PD-MCI, PD-NC patients and healthy controls, and was correlated with white matter hyperintensities on magnetic resonance imaging. All abnormal neuropsychological test results were associated with increased urine protein/creatinine ratio. After controlling for age, education, symptom duration, diabetes mellitus, hypertension, and parkinsonian motor severity, the urine protein/creatinine ratio was significantly associated with decreased cognition., Conclusion: The urine protein/creatinine ratio was associated with cognitive status in LBD. These finding suggests that increased protein excretion is associated with cognitive dysfunction in patients with LBD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Brain-derived neurotrophic factor (BDNF) and cognitive function are diminished in people with Parkinson's disease (PD). The relationship of cognitive function and serum level of BDNF, however is yet to be examined. The aim of this study was to examine serum BDNF levels in PD. Subsequently, the relationship of cognitive function to the serum levels of BDNF was evaluated., Methods: Serum BDNF levels were measured in 29 idiopathic PD subjects and 30 healthy-matched controls using ELISA technique. Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA) scale., Results: Serum BDNF levels and MOCA total score were significantly lower (P<0.001) in PD patients versus healthy controls. MOCA total score correlated with serum BDNF (r=0.44; P=0.012) but not with age, years of education, duration of disease and severity of symptoms. The regression analysis showed that serum BDNF accounted (P=0.019) for 19% of MOCA total score variance., Conclusions: The data confirm lowered serum BDNF in PD. Additionally; it suggests that BDNF may play a role in the cognitive deficit of PD. Further studies are required to identify association of BDNF in cognitive decline with PD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: High-intensity resistance training is unexplored in people with multiple sclerosis., Objectives: To evaluate effects of high-intensity resistance training on immune markers and on measures of mood, fatigue, health-related quality of life, muscle strength, walking and cognition. Further, to describe participants' opinion and perceived changes of the training., Methods: Twenty patients with relapsing-remitting multiple sclerosis performed high-intensity resistance training at an intensity of 80% of one-repetition maximum, twice a week for 12 weeks. Blood and optional cerebrospinal fluid samples, and data on secondary outcome measures were collected before and after intervention. A study-specific questionnaire was used for capturing participants' opinion., Results: Seventeen participants completed the study. Plasma cytokine levels of tumor necrosis factor were significantly decreased post-intervention (p=0.001). Exploratory cytokine analyses in cerebrospinal fluid (n=8) did not reveal major changes. Significant and clinically important improvements were found in fatigue (p=0.001) and health-related quality of life (p=0.004). Measures of mood (p=0.002), muscle strength (p ≤ 0.001), walking speed (p=0.013) and cognition (p=0.04) were also improved. A majority of participants evaluated the training as very good and perceived changes to the better., Conclusion: High-intensity resistance training in persons with relapsing remitting multiple sclerosis with low disability had positive effects on peripheral pro-inflammatory cytokine levels, led to clinically relevant improvements in measures of fatigue and health-related quality of life, and was well tolerated. These results provide a basis for a larger randomized trial., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Given the high prevalence of cognitive dysfunction in people with multiple sclerosis (PWMS) and the lack of availability of specialized neuropsychological services in most MS Clinics, there is a need for a brief cognitive monitoring tool that can be easily administered by MS clinic staff., Objective: We aimed to establish the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) as a feasible cognitive monitoring tool and provide Canadian data toward the international validation effort. Secondary considerations were to determine if BICAMS correlates with self-reported cognition and predicted vocational status., Methods: 57 PWMS were matched to 51 healthy controls (age, sex, education). Participants completed the BICAMS battery which includes the Symbol Digit Modalities Test, and the learning trials from the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. Depression, self-reported cognition, and fatigue were assessed. Participants were re-tested 15.6 (SD 2.0) days later., Results: With impairment defined as "one or more abnormal tests," 57.9% of MS sample was cognitively impaired. Participants were more likely to be impaired on the BVMT-R (43.9%). On the SDMT and CVLT-II, 28.1% and 26.3% of MS participants were impaired. Sensitivity and specificity were highest for the SDMT. The BICAMS was reliable over time (r value range from 0.69 for BVMT-R to 0.87 for SDMT) with the SDMT being most robust. There was no relationship between BICAMS and subjective cognition. The BVMT-R reliably predicted employment., Conclusions: The BICAMS detected cognitive impairment to a comparable degree to more comprehensive neuropsychological batteries and is a valid measure of cognition in MS. Reliability of components varies, suggesting care be taken when interpreting serial testing results. The BICAMS is a feasible cognitive assessment tool in Canadians and yields comparable results to other cultures., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Patients with severe steno-occlusive disease of a main cerebral artery may demonstrate cognitive impairment without identification of causative lesions on magnetic resonance imaging. We investigated whether cognitive impairment in these patients is associated with regional cerebral blood flow (rCBF), leukoaraiosis, risk factors of atherosclerosis and cerebrovascular reserve (CVR), which shows so-called clinical neurovascular function., Methods: In 65 patients with severe steno-occlusive disease of an internal carotid artery or a middle cerebral artery (MCA) and no cerebral infarction (CI), we examined cognitive function with COGNISTAT, grades of leukoaraiosis, and CBF and CVR as calculated by iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography and blood data. We compared such values of the left and right sided diseases. rCBF and CVR on the affected side were compared to other side., Results: Logistic regression analysis revealed that CVR correlated with cognitive impairment. There was no significant difference in rCBF, CVR, or COGNISTAT score when comparing the left and right sided diseases. There were good correlations between CBF or CVR of the ipsilateral MCA area and ipsilateral and contralateral other areas., Conclusion: Cognitive impairment is associated with CVR in the whole brain. Nonselective widespread neurovascular mild dysfunction can be a reason for cognitive impairment in patients with severe steno-occlusive disease of a main cerebral artery and no CI., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Midlife cerebrovascular risk, low cognitive reserve and APOE4+ haplotypes are risk factors for Alzheimer's disease dementia (AD). We prospectively searched for factors that might be associated with yearly changes in caregiver burden, cognition, basic and instrumental functionality in 193 consecutive outpatients with late-onset AD, namely gender, APOE haplotypes, schooling, age at AD onset, marital status, depression, cerebrovascular risk factors, serum TSH levels, cognitive and physical activities, and treatment with cholinesterase inhibitors or anti-psychotics, while also investigating associations between APOE haplotypes and patient participation in cognitive or physical activities. Higher education led to greater declines in instrumental functionality, whereas increases in body mass index were associated with rises in basic functionality and cognitive test scores. Established cerebrovascular risk factors had no independent effects over cognitive or functional change, but their combinations led to cognitive improvement, possibly related to enhanced cerebral perfusion in late life. Cholinesterase inhibitors improved caregiver burden. Enhanced instrumental functionality and steeper cognitive decline by the use of anti-psychotics might be attributed to improved behavioural symptoms and neuropsychiatric side effects, respectively. Each copy of APOE-ε4 (β=-0.102) led to cumulative decreased participation in physical activities (ρ=0.015). These results might impact public health policies and the interpretation of clinical trials for AD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The assessment of cognitive impairment in multiple sclerosis (MS) requires large neuropsychological batteries that assess numerous domains. The relevance of these assessments to daily cognitive functioning is not well established. Cognitive ecological evaluation has not been frequently studied in MS., Objectives: The aim of this study was to determine the interest of cognitive evaluation in a virtual reality environment in a sample of persons with MS with cognitive deficits., Methods: Thirty persons with MS with at least moderate cognitive impairment were assessed with two ecological evaluations, an in-house developed task in a virtual reality environment (Urban DailyCog®) and a divided attention task in a driving simulator. Classical neuropsychological testing was also used., Results and Conclusion: Fifty-two percent of the persons with MS failed the driving simulator task and 80% failed the Urban DailyCog®. Virtual reality assessments are promising in identifying cognitive impairment in MS., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Objective: Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA) and cognitive impairment. Uric acid has an anti-oxidative effect. Our objective is to clarify the correlations between serum uric acid and cognitive function as well as frontal lobe function in Chinese MSA patients., Methods: All of MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Unified MSA Rating Scale (UMSARS). The fasting serum uric acid concentrations of MSA patients were measured., Results: A total of 89 probable MSA patients with a mean age of 58.6 ± 10.0 years old and disease duration of 2.6 ± 1.5 years were included. Thirty-three patients (37.1%) had global cognitive deficits according to ACE-R. Based on FAB, 35 patients (39.3%) had frontal lobe dysfunction. After adjusting for educational years, patients with cognitive deficits had lower uric acid level than patients without cognitive deficits. Patients with frontal lobe dysfunction had lower uric acid level after adjusting for UMSARS scores. In a forward multiple linear regression, uric acid level and educational years were the variables predicting the ACE-R score (F=36.540, R(2)=0.459, p=0.0001), uric acid accounting for 14% of the total variables. Uric acid was the only variable contributing to the FAB score (F=18.551, R(2)=0.176, p=0.0001)., Conclusion: Our study suggested that low level of serum uric acid was associated with cognitive deficits in MSA. Low uric acid level predicting cognitive decline in MSA needs more studies., (Copyright © 2015. Published by Elsevier B.V.)

Objectives: The purpose of this study was to evaluate cognitive function in patients with multiple sclerosis (MS), compared with control subjects, and to establish whether decline of cognitive function continues in the patients during remission., Methods: The Japanese version of the Brief Repeatable Battery of Neuropsychological tests (BRB-N), which includes the selective reminding test (SRT), spatial recall test (SPART), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), and the word list generation test (WLG), was performed in 34 Japanese patients with MS (8 males, 26 females; mean age, 42 years) and in 37 age- and education-matched healthy controls (20 males, 17 females; mean age, 36 years). BRB-N was conducted at intervals of two years for MS patients who remained in remission, and the cognitive changes were evaluated by comparing the results with those of the initial examination at entry into the study., Results: The MS patients showed lower BRB-N scores than controls, with high significance in the SRT, SRT-D, SDMT and PASAT tests (p<0.01). The BRB-N scores of the MS patients who remained in remission were not significantly changed for at least 2 years., Conclusions: The Japanese version of the BRB-N is useful to clarify the nature of cognitive impairment in Japanese MS patients. Based on this neuropsychological assessment, we suggest that working memory and information-processing speed are key deficits. Patients who remained in remission showed little or no further impairment of cognitive functions for at least two years., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim: Childhood absence epilepsy (CAE) is a paediatric epilepsy syndrome characterized by typical absence seizures in school age children. Although it is commonly considered to have a good prognosis, with a good response to antiepileptic drugs, recent studies questioned this traditional view of a “benign” disorder, in particular regarding neuropsychological functioning. The aim of this study is to review the neuropsychological involvement in patients affected by CAE., Methods: A literature search was carried out in PubMed's and Medline's databases for all relevant studies published between 1924 and 2014. The keywords used were neuropsychology, absence seizures, and CAE. Specific review articles, systematic reviews, textbooks and case reports were examined for any further publications., Results: In intellectual functioning, CAE patients seem to perform worse than healthy children, even if their IQ scores fall within the normal range. Similarly, CAE seems to affect verbal skills and learning. Executive functions have been reported to be mildly impaired. Data regarding memory are still conflicting., Discussion: Given the neuropsychological deficits in many CAE patients which significantly affect their quality of life, CAE should not be considered entirely “benign”. An early identification of neuropsychological dysfunction in CAE children is essential for appropriate treatment.