Profile of and risk factors for poststroke cognitive impairment in diverse ethno-regional groups

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethno-racial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethno-racial differences that warrant attention in the development of prevention strategies.OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.Peer reviewe

Diabetes Mellitus and Cognition: A Pathway Analysis in the MEMENTO Cohort

OBJECTIVE: To assess the role of biomarkers of Alzheimer's Disease (AD), neurodegeneration and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. METHODS: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent or self-report. We used structural equation modelling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ(42)/Aβ(40) ratio and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (five neuropsychological tests), adjusting for potential confounders. RESULTS: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089; -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. CONCLUSION: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers

Influence of medication on fatigue six months after stroke

International audiencePoststroke fatigue (PSF) is frequent and affects patients' quality of life. Medication use was hypothesized as being responsible for PSF. Our objective was to evaluate potential relationships between 6-month PSF and medication use at discharge and 6 months after an ischemic stroke. This study is part of STROKDEM, an ongoing longitudinal cohort study, whose main aim is to determine predictors of poststroke dementia. Patients were included within 72 hours after an ischemic stroke and followed up with standardized evaluations. Medication use 7 days and 6 months after stroke was rated, and polypharmacy was defined as the number of categories of treatments received by a patient. PSF was evaluated using the Chalder Fatigue Scale. Medical history, vascular risk factors, depression, anxiety, and sleep disturbances were evaluated. One hundred and fifty-three patients were included: 52.9% presented PSF. PSF at 6 months was not predicted by medication use at discharge nor associated with medication use at month 6. We found severity of PSF to be increased in patients with polypharmacy. Our results suggest that PSF is not a side effect of drugs use, which more reflects presence of disturbances frequently observed after stroke such as depression, anxiety, or sleep disturbances. Clinical study is registered on clinicaltrials.gov (NCT01330160)

Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke

Objective To examine whether the Montreal Cognitive Assessment (MoCA) administered within 7 days after stroke predicts long-term cognitive impairment, functional impairment, and mortality. Methods MoCA was administered to 274 patients from 2 prospective hospital-based cohort studies in Germany (n = 125) and France (n = 149). Cognitive and functional outcomes were assessed at 6, 12, and 36 months after stroke by comprehensive neuropsychological testing, the Clinical Dementia Rating (CDR) scale, the modified Rankin Scale (mRS), and Instrumental Activities of Daily Living (IADL) and analyzed with generalized estimating equations. All-cause mortality was investigated by Cox proportional hazard models. Analyses were adjusted for demographic variables, education, vascular risk factors, premorbid cognitive status, and NIH Stroke Scale scores. The additive predictive value of MoCA was examined with receiver operating characteristic curves. Results In pooled analyses, a baseline MoCA score = 0.5 (OR 2.53, 95% CI 153-4.18);functional impairment, defined by mRS score >2 (OR 5.03, 95% CI 2.20-11.51) and by LADL score 2, 0.88 vs 0.84, p = 0.047). Conclusion Early cognitive testing by MoCA predicts long-term cognitive outcome, functional outcome, and mortality after stroke. Our results support routine use of the MoCA in stroke patients

Functional connectivity correlates of reduced goal-directed behaviors in behavioural variant frontotemporal dementia

International audienceWe explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD). We recorded the behavior of 20 bvFTD patients and 16 healthy controls in a close-to-real-life situation including a free phase (FP-in which actions were self-initiated) and a guided phase (GP-in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy. We used the means ((FP + GP)/2) and the differences (FP-GP) calculated for these metrics as well as measures by questionnaires to extract apathy dimensions by factor analysis. We assessed two types of fMRI-based resting state connectivity measures (local activity and seed-based connectivity) and explored their relationship with extracted apathy dimensions. Apathy in bvFTD was associated with lower time spent in activity combined with walking episodes of higher frequency, lower acceleration and higher duration. Using these behavioral metrics and apathy measures by questionnaires, we disentangled two dimensions: the global reduction of goal-directed behaviors and the specific deficit of self-initiation. Global apathy was associated with lower resting state activity within prefrontal cortex and lower connectivity of salience network hubs while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. Through a novel dimensional approach, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. We discussed in particular the role of the modified connectivity of lateral parietal cortex in the volitional process

Tau as a biomarker of neurodegenerative diseases.

International audienceThe microtubule-associated protein Tau is mainly expressed in neurons of the CNS and is crucial in axonal maintenance and axonal transport. The rationale for Tau as a biomarker of neurodegenerative diseases is that it is a major component of abnormal intraneuronal aggregates observed in numerous tauopathies, including Alzheimer's disease. The molecular diversity of Tau is very useful when analyzing it in the brain or in the peripheral fluids. Immunohistochemical and biochemical characterization of Tau aggregates in the brain allows the postmortem classification and differential diagnosis of tauopathies. As peripheral biomarkers of Alzheimer's disease in the cerebrospinal fluid, Tau proteins are now validated for diagnosis and predictive purposes. For the future, the detailed characterization of Tau in the brain and in peripheral fluids will lead to novel promising biomarkers for differential diagnosis of dementia and monitoring of therapeutics

Cerebrospinal fluid Alzheimer biomarkers can be useful for discriminating dementia with Lewy bodies from Alzheimer’s disease at the prodromal stage

International audienceBackground Differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) is not straightforward, especially in the early stages of disease. We compared AD biomarkers (phospho-Tau 181 , total-Tau, Aβ42 and Aβ40) in cerebrospinal fluid (CSF) of patients with DLB and AD, focusing especially on the prodromal stage. Methods A total of 1221 CSF were collected in different memory centres (ePLM network) in France and analysed retrospectively. Samples were obtained from patients with prodromal DLB (pro-DLB; n=57), DLB dementia (DLB-d; n=154), prodromal AD (pro-AD; n=132) and AD dementia (n=783), and control subjects (CS; n=95). These centres use the same diagnostic procedure and criteria to evaluate the patients. Results In patients with pro-DLB, CSF Aβ42 levels appeared much less disrupted than in patients at the demented stage (DLB-d) (Ppro-DLB; PDLB-d). On average, Aβ40 levels in patients with DLB (pro-DLB and DLB-d) were much below those in patients with pro-AD (P<0.001 DLB groups<pro-AD). The Aβ42/Aβ40 ratio in patients with pro-DLB remained close to that of CS. t-Tau and phospho-Tau 181 levels were unaltered in patients with DLB (pro-DLB and DLB-d). Conclusions Reduced levels of CSF Aβ42 were found in patients with DLB but rather at a later stage, reaching those of patients with AD, in whom Aβ42 levels were decreased even at the prodromal stage. At the prodromal stage of DLB, the majority of patients presented a normal CSF profile. CSF t-Tau and phospho-Tau 181 were the best biomarkers to discriminate between AD and DLB, whatever the stage of disease

Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers

International audienc