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Purpose: Social cognition disorders after stroke are poorly described. Yet, rehabilitation difficulties are frequent after stroke. This study aimed to evaluate the frequency of social cognition disorders 3 years after a first-ever stroke and to assess the factors associated with this condition. The second aim was to describe all the cognitive domains altered in the same population., Methods: Patients who suffered from a first-ever ischemic or hemorrhagic stroke underwent clinical and neuropsychological assessment, which included the mini-Social cognition and Emotional Assessment (SEA) for evaluating social cognition., Results: The 43 included patients were 67±15 years old, with a median Neurological Institute of Health Stroke Scale (NIHSS) (± interquartile range) at 0±1, and a median modified Rankin Scale (± interquartile range) at 1±1. Twenty patients (46.5%) had poor results in the facial emotions subtest; this factor was associated with a low educational grade (P=0.001). Fourteen patients (34.2%) had poor results on the "faux-pas" recognition subtest; this factor was associated with nonverbal episodic memory disorders (P=0.01). Thirty four patients (79.1%) had cognitive impairment, with at least 1 cognitive domain affected., Conclusions: The study demonstrates the high frequency of social cognition impairment 3 years after the first-ever stroke in young patients. Doctors and nurses should be sensitized to cognitive handicap after stroke because of difficulties for rehabilitation and returning to work.

Objectives: Aging entails deterioration in sensory, physical, and cognitive functions, raising doubt in the driving capacity of older drivers, especially when the deficits are severe, as in dementia. Many older drivers, especially women, adapt their driving habits in order to compensate for these deficits and eventually stop driving. The present prospective study assessed driving cessation in men and women throughout the dementia process, including a 2-year pre-dementia phase., Methods: The study was based on a three-city cohort of subjects who were aged 65 years and older in 2000 and followed for more than 10 years. Active dementia detection was conducted at each follow-up. The probability of driving cessation was assessed in men and women during the 2-year pre-dementia phase and until 5 years after diagnosis., Results: In the 2-year pre-dementia phase, both men and women ceased driving earlier than drivers with no central nervous system pathology (p < 0,001), and women ceased driving earlier than men. A total of 45% of men and 74% of women had already ceased driving at dementia diagnosis. In contrast, the probability of cessation within 3 years after diagnosis was similar between men and women., Conclusion: The study showed that, in this French urban population, few demented drivers, especially women, were still driving after diagnosis. Those who continued to drive 3 years after the diagnosis all had Alzheimer-type dementia. There is certainly a need for physicians to help these drivers to adapt their driving activity to their deficits and to prepare them to stop driving. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: A growing body of evidence supports a beneficial role for vitamin K in brain and cognition, notably in studies where animals are rendered vitamin K deficient by warfarin, a potent vitamin K antagonist (VKA). Given VKAs are commonly used oral anticoagulants in older persons, we investigated the relationship between VKA therapy and cognitive performances over 10 years in participants of the Three-City study., Methods: The Three-City cohort included 7,133 nondemented community dwellers, aged 65 years or older at baseline. Exposures to VKAs and platelet aggregation inhibitors, another antithrombotic agent, were determined at baseline. Participants underwent cognitive assessment at baseline and every 2 years over 10 years. Associations were analyzed with mixed linear models adjusting for many covariates including VKA and platelet aggregation inhibitor indications., Results: About 239 (3.4%) and 1,192 (16.7%) of the participants were treated with VKAs and platelet aggregation inhibitors at baseline, respectively. VKA treatment was significantly associated with worse performances on Benton Visual Retention Test assessing visual memory (adjusted mean difference -0.29; p = .02 in multivariate models) and Isaacs Set Test assessing verbal fluency (adjusted mean difference -1.37; p = .0009) at baseline. Treatment with VKAs was not associated with global cognitive functioning on the Mini Mental State Examination, neither with rate of subsequent decline in scores on all three cognitive tests. No associations were found between platelet aggregation inhibitors and cognitive performances or rate of decline., Conclusion: These findings do not indicate a long-term detrimental effect of VKAs on cognition, but the risk-benefit balance of VKA treatment still deserves further research., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study was to examine the associations between serum lipid levels and cognitive function in a community-based sample of non-demented subjects aged 65 years and over. Participants were 2737 men and 4118 women from a population-based cohort recruited from three French cities. Visual memory, verbal fluency, psychomotor speed, and executive abilities were evaluated at baseline, and after 2, 4, and 7 years of follow-up. Lipid levels were evaluated at baseline. Multiadjusted Cox models stratified by gender were adjusted for sociodemographic and lifestyle characteristics, mental and physical health, and genetic vulnerability to dyslipidemia (apolipoprotein E and A, and cholesteryl ester transfer protein) and taking into account baseline vascular pathologies. In men, a hypercholesterolemic pattern in late-life (high total cholesterol (T-C), low HDL-C, high LDL-C levels) was associated with a 25 to 50% increased risk of decline over 7 years in psychomotor speed, executive abilities, and verbal fluency. Specific associations with low T-C and low LDL-C levels were also observed which may depend on genetic vulnerability to dyslipidemia (related to apolipoprotein A5 and cholesteryl exchange transfer protein). In contrast, in women, a 30% higher rate of decline was found in psychomotor speed with high HDL-C levels and in executive abilities with low levels of LDL-C and triglycerides, in interaction with hormonal treatment. For men and women, vascular pathologies only slightly outweighed the risk related to lipids. This suggests a complex gender-specific pattern of cognitive decline involving genetic vulnerability in men and hormonal status in women., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

Background: Numerous studies suggest that higher coffee consumption may reduce the rate of aging-related cognitive decline in women. It is thus potentially a cheap and widely available candidate for prevention programs provided its mechanism may be adequately understood. The assumed effect is that of reduced amyloid deposition, however, alternative pathways notably by reducing depression and diabetes type 2 risk have not been considered., Methods: A population study of 1,193 elderly persons examining depressive symptomatology, caffeine consumption, fasting glucose levels, type 2 diabetes onset, serum amyloid, and factors known to affect cognitive performance was used to explore alternative causal models., Results: Higher caffeine consumption was found to be associated with decreased risk of incident diabetes in men (HR = 0.64; 95% CI 0.42-0.97) and increased risk in women (HR = 1.51; 95% CI 1.08-2.11). No association was found with incident depression. While in the total sample lower ratio Aβ42/Aβ40 levels (OR = 1.36, 95% CI 1.05-1.77, p = 0.02) were found in high caffeine consumers, this failed to reach significance when the analyses were stratified by gender., Conclusions: We found no evidence that reduced risk of cognitive decline in women with high caffeine consumption is moderated or confounded by diabetes or depression. The evidence of an association with plasma beta amyloid could not be clearly demonstrated. Insufficient proof of causal mechanisms currently precludes the recommendation of coffee consumption as a public health measure. Further research should focus on the high estrogen content of coffee as a plausible alternative explanation.

Background: Because of the aging population and a rise in the number of stroke survivors, the prevalence of post-stroke cognitive impairment (PSCI) is increasing., Objective: To identify the factors associated with 3-month PSCI., Methods: All consecutive stroke patients without pre-stroke dementia, mild cognitive disorders, or severe aphasia hospitalized in the Neurology Department of Dijon, University Hospital, France (November 2010 - February 2012) were included in this prospective cohort study. Demographics, vascular risk factors, and stroke data were collected. A first cognitive evaluation was performed during the hospitalization using the Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MOCA). Patients assessable at 3 months were categorized as cognitively impaired if the MMSE score was ≤26/30 and MOCA <26/30 or if the neuropsychological battery confirmed PSCI when the MMSE and MOCA were discordant. Multivariable logistic models were used to determine factors associated with 3-month PSCI., Results: Among the 280 patients included, 220 were assessable at 3 months. The overall frequency of 3-month PSCI was 47.3%, whereas that of dementia was 7.7%. In multivariable analyses, 3-month PSCI was associated with age, low education level, a history of diabetes mellitus, acute confusion, silent infarcts, and functional handicap at discharge. MMSE and MOCA scores during hospitalization were associated with 3-month PSCI (OR = 0.63; 95% CI: 0.54-0.74; p < 0.0001 and OR = 0.67; 95% CI: 0.59-0.76; p < 0.0001, respectively)., Conclusion: Our study underlines the high frequency of PSCI in a cohort of mild stroke. The early cognitive diagnosis of stroke patients could be useful by helping physicians to identify those at a high risk of developing PSCI.

A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23-2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12-1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05-1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted., (Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.)

The aim of this study was to evaluate the effects of anti-inflammatory intake on cognitive function in 7234 community-dwelling elderly persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated at baseline, and 2, 4, and 7 years later. Multivariate logistic regression analyses were adjusted for sociodemographic, behavioral, physical, mental health variables, and genetic vulnerability (apolipoprotein E ε4). Elderly women taking inhaled corticosteroids were at increased risk for cognitive decline over 7 years in executive functioning (odds ratio, 1.76; 95% confidence interval, 1.14-2.71; p = 0.04); the effect being increased after continuous use (odds ratio, 3.15; 95% confidence interval, 1.29-7.68; p = 0.01) and not found after discontinuation of treatment. In men, no significant associations were observed. Corticosteroid use was not significantly associated with an increase risk of incident dementia over 7 years. Nonsteroidal anti-inflammatory drug use was not significantly associated with either dementia incidence or cognitive decline in both sexes. The association may be related to hypothalamic-pituitary-adrenal corticotropic axis dysfunctioning rather than a direct anti-inflammatory mechanism. Long-term use of inhaled corticosteroids may constitute a form of reversible cognitive disorder in elderly women. Physicians should check this possibility before assuming neurodegenerative changes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aim of this prospective cohort study was to evaluate the effects of lipid lowering agent (LLA) intake on cognitive function in 6,830 community-dwelling elderly persons. Cognitive performance (global cognitive functioning, visual memory, verbal fluency, psychomotor speed, and executive function), clinical diagnosis of dementia, and fibrate and statin use, were evaluated at baseline, and 2, 4, and 7 year follow-up. Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics, mental and physical health including vascular risk factors, and genetic vulnerability (apolipoprotein E and cholesteryl ester transfer protein). For women but not men, fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only (HR = 1.29, 95% CI = 1.09-1.54, p = 0.004), and did not increase risk for incident dementia. This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate (HR = 1.39, 95% CI = 1.08-1.79, p = 0.01) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment. For both genders, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence. This prospective study, adjusting for multiple confounders, found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia, but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory.

Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.

Our objective was to investigate the influence of hypertension on N-acetylaspartate (NAA) and choline (Cho) ratios in brain tissues in a community-dwelling elderly population. Brain flexibility was also evaluated with regard to the same metabolite ratios. Proton magnetic resonance spectroscopy (MRS) and the Trail Making Test (TMT) were performed in 80 subjects (75.7+/-4 years old) from the Three-City Study. Fifty-eight participants had hypertension. The NAA/creatine (Cr) and Cho/Cr ratios were obtained in the insular cortex, the thalami and the deep periventricular white matter. In addition, the B-A score of the TMT was evaluated. Uni- and multi-variate analyses were performed in order to examine the relationships among these data. In the insula and the thalami of the hypertensive group, NAA/Cr ratios were significantly lower (1.39+/-0.23 and 1.52+/-0.23, respectively; p=0.01) than those in the normotensive control group (1.52+/-0.25 and 1.70+/-0.19, respectively; p<0.0001), whereas no such reduction was observed in the periventricular white matter of older hypertensive brains. Moreover, the NAA or Cho ratios were significantly correlated with the TMT B-A scores at the level of the thalami, insula and periventricular white matter. These statistical results were confirmed by the multivariate analysis. In an elderly population, hypertension leads to a reduction in NAA/Cr ratios in the insula and the thalami, possibly due to a decrease in blood flow through small perforating and cortical arteries. The TMT B-A test appears to be relevant not only for the frontal areas but also for more remote areas such as the thalami, the insula and the deep periventricular white matter.

Objective: To examine risk factors for mild cognitive impairment (MCI) and progression to dementia in a prospective community-based study of subjects aged 65 years and over., Methods: 6892 participants who were over 65 and without dementia were recruited from a population-based cohort in three French cities. Cognitive performance, clinical diagnosis of dementia, and clinical and environmental risk factors were evaluated at baseline and 2-year and 4-year follow-ups., Results: 42% of the population were classified as having MCI at baseline. After adjustment for confounding with logistic regression models, men and women classified as having MCI were more likely to have depressive symptomatology and to be taking anticholinergic drugs. Men were also more likely to have a higher body mass index, diabetes and stroke, whereas women were more likely to have poor subjective health, to be disabled, to be socially isolated, and to suffer from insomnia. The principal adjusted risk factors for men for progression from MCI to dementia in descending order were ApoE4 allele (OR = 3.2, 95% CI 1.7 to 5.7), stroke (OR = 2.8, 95% CI 1.2 to 6.9), low level of education (OR = 2.3, 95% CI 1.3 to 4.1), loss of Instrumental Activities of Daily Living (IADL) (OR = 2.2, 95% CI 1.1 to 4.5) and age (OR = 1.2, 95% CI 1.1 to 1.2). In women, progression is best predicted by IADL loss (OR = 3.5, 95% CI 2.1 to 5.9), ApoE4 allele (OR = 2.3, 95% CI 1.4 to 4.0), low level of education (OR = 2.2, 95% CI 1.3 to 3.6), subclinical depression (OR = 2.0, 95% CI 1.1 to 3.6), use of anticholinergic drugs (OR = 1.8, 95% CI 1.0 to 3.0) and age (OR = 1.1, 95% CI 1.1 to 1.2)., Conclusions: Men and women have different risk profiles for both MCI and progression to dementia. Intervention programmes should focus principally on risk of stroke in men and depressive symptomatology and use of anticholinergic medication in women.

Objective: To examine the association between caffeine intake, cognitive decline, and incident dementia in a community-based sample of subjects aged 65 years and over., Methods: Participants were 4,197 women and 2,820 men from a population-based cohort recruited from three French cities. Cognitive performance, clinical diagnosis of dementia, and caffeine consumption were evaluated at baseline and at 2 and 4 year follow-up., Results: Caffeine consumption is associated with a wide range of sociodemographic, lifestyle, and clinical variables which may also affect cognitive decline. Multivariate mixed models and multivariate adjusted logistic regression indicated that women with high rates of caffeine consumption (over three cups per day) showed less decline in verbal retrieval (OR = 0.67, CI = 0.53, 0.85), and to a lesser extent in visuospatial memory (OR = 0.82, CI = 0.65, 1.03) over 4 years than women consuming one cup or less. The protective effect of caffeine was observed to increase with age (OR = 0.73, CI = 0.53, 1.02 in the age range 65 to 74; OR = 0.3, CI = 0.14, 0.63 in the range 80+). No relation was found between caffeine intake and cognitive decline in men. Caffeine consumption did not reduce dementia risk over 4 years., Conclusions: The psychostimulant properties of caffeine appear to reduce cognitive decline in women without dementia, especially at higher ages. Although no impact is observed on dementia incidence, further studies are required to ascertain whether caffeine may nonetheless be of potential use in prolonging the period of mild cognitive impairment in women prior to a diagnosis of dementia.

Introduction: Multiple sclerosis (MS) is a major cause of neurological disability among young adults. The cognitive disorders are the second cause of alteration of quality of life after physical handicap and are often responsible for loss of social-occupational adaptability. The prevalence of cognitive disorders is 40 to 65%. The alteration of executive functions predominates whereas instrumental functions are generally preserved. The assessment of these disorders is often underestimated by the usual battery of neuropsychological tests. However, the link between psychometric results and executive difficulties of daily life is uncertain., Objectives: To evaluate the sensitivity of an ecological test compared to standard psychometric tests in assessment of executive disorders in MS., Methods: Twenty subjects with clinically definite MS were matched for age, sex and pre-morbid intellectual level with control subjects. A battery of neuropsychological and ecological tests was applied to all subjects. The performances on these tests formed a global score of executive function (SFE). The "paper and pencil" multiple errands test was used as the ecological test to examine planning and goal-oriented behavior. We also assessed fatigue and depression with the Fatigue Severity Scale and the Beck Depression Inventory., Results: There was no significant differences between MS patients and controls in neuropsychological executive tests, except for verbal fluencies (p=0.01). The performances were significantly decreased in the MS group for the multiple errands test (p=0.01). 75% of MS subjects have a pathological score for this test. There was a significant link between the performances with this test and SFE (p=0.009)., Conclusions: Executive disorders are underestimated in MS. However, we suggest that an ecological approach is more reliable than standard neuropsychological tests to estimate the cognitive difficulties in daily life in MS subjects. The results of our study favor further research to ascertain the usefulness of ecological assessment in MS.