Network impact score is an independent predictor of post-stroke cognitive impairment: A multicenter cohort study in 2341 patients with acute ischemic stroke

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction. AIMS: To determine if the network impact score is an independent predictor of PSCI, and of cognitive recovery or decline. METHODS: We pooled data from patients with acute ischemic stroke from 12 cohorts through the Meta VCI Map consortium. PSCI was defined as impairment in ≥ 1 cognitive domain on neuropsychological examination, or abnormal Montreal Cognitive Assessment. Cognitive recovery was defined as conversion from PSCI 24 months) and cognitive recovery or decline using logistic regression. Models were adjusted for age, sex, education, prior stroke, infarct volume, and study site. RESULTS: We included 2341 patients with 4657 cognitive assessments. PSCI was present in 398/844 patients (47%) 24 months. Cognitive recovery occurred in 64/181 (35%) patients and cognitive decline in 26/287 (9%). The network impact score predicted PSCI in the univariable (OR 1.50, 95%CI 1.34-1.68) and multivariable (OR 1.27, 95%CI 1.10-1.46) GEE model, with similar ORs in the logistic regression models for specified post-stroke intervals. The network impact score was not associated with cognitive recovery or decline. CONCLUSIONS: The network impact score is an independent predictor of PSCI. As such, the network impact score may contribute to a more precise and individualized cognitive prognostication in patients with ischemic stroke. Future studies should address if multimodal prediction models, combining the network impact score with demographics, clinical characteristics and other advanced brain imaging biomarkers, will provide accurate individualized prediction of PSCI. A tool for calculating the network impact score is freely available at https://metavcimap.org/features/software-tools/lsm-viewer/

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

Rôle de la dysfonction endothéliale dans les troubles cognitifs pré-AVC

Les troubles cognitifs pré-AVC, peu explorés, peuvent impacter la récupération motrice et cognitive post-AVC. Deux hypothèses sont actuellement avancées quant à leur origine. La première hypothèse est qu’ils pourraient être la traduction d’une pathologie neurodégénérative sous-jacente. La seconde hypothèse serait en faveur d’un mécanisme vasculaire en lien avec les facteurs de risque tels que l’HTA ou le diabète. Pour étayer cette seconde hypothèse, nous avons étudié la fonction endothéliale de 86 patients hospitalisés pour un AVC ischémique. Ces patients ont bénéficié d’une mesure de la fonction endothéliale par pléthysmographie digitale, de dosage de biomarqueurs reflet des fonctions de l’endothélium et d’une évaluation cognitive pré et post AVC. Nous avons pu montrer l’association entre la dysfonction endothéliale mesurée au décours de l’AVC et l’existence de troubles cognitifs préexistants. Un index bas de RHI, marqueur de la dysfonction endothéliale, était associé à un score élevé à l’IQ-Code, outil de dépistage des difficultés cognitives pré-AVC. Lorsque la dysfonction endothéliale était présente, elle était le plus souvent associée à l’existence d’une HTA, mais il n’existait pas d’association avec le diabète ou une dyslipidémie. Des anomalies de la substance blanche et une atrophie cérébrale étaient également associées à une altération de la fonction endothéliale. Cette dysfonction endothéliale était associée à une inflammation vasculaire mise en évidence par la variation de marqueurs de l’interaction leucocytes-endothélium et de l’homocystéine. Nous n’avons pas mis en évidence d’association entre la dysfonction endothéliale et le pronostic cognitif à 6 mois. L’ensemble des résultats permettent de confirmer le lien entre dysfonction endothéliale, troubles cognitifs préexistants et facteurs de risque vasculaire. Le dépistage et le suivi de la mesure de la fonction endothéliale pourrait être un outil d’optimisation de la prise en charge des facteurs de risque vasculaire, pour prévenir le risque cognitif à long terme, au-delà de la prévention des accidents vasculaires cardiaques et cérébraux

Which factors influence the resort to surrogate consent in stroke trials, and what are the patient outcomes in this context?

International audienceBACKGROUND:The provision of informed consent is a prerequisite for inclusion of a patient in a clinical research project. In some countries, the legislation on clinical research authorizes a third person to provide informed consent if the patient is unable to do so directly (i.e. surrogate consent). This is the case during acute stroke, when the symptoms may prevent the patient from providing informed consent and thus require a third party to be approached. Identification of factors associated with the medical team's decision to resort to surrogate consent may (i) help the care team during the inclusion process and (ii) enable the patient's family circle to be better informed (and thus feel less guilty) about providing surrogate consent.METHODS:Patients included in the BIOSTROKE cohort (initially dedicated to the analysis of factors influencing stroke severity) were divided into two groups: those having provided informed consent directly and those for whom a third party (such as a family member) had provided surrogate consent. We compared the groups in terms of the initial clinical characteristics (age, gender, type of stroke, severity on the National Institutes of Health Stroke Scale (NIHSS), pre-stroke cognitive status according to the Informant Questionnaire on Cognitive Decline in the Elderly, and the stroke's aetiology) and the functional and cognitive impairments (according to the NIHSS, the modified Rankin score (mRS) and the Mini Mental State Examination) on post-stroke days 8 and 90.RESULTS:Three hundred and ninety five patients were included (mean ± SD age: 67 ± 15 years; 53% males). Surrogate consent had been obtained in 228 cases, and 167 patients had provided consent themselves. The patients included with surrogate consent were likely to be older and more aphasic, with a pre-existing cognitive disorder and more severe stroke (relative to the patients having provided consent). In terms of recovery, the patients included with surrogate consent had a worse functional prognosis (day 90 mRS ≥3: 57.6%, compared with 16.8% in patients having provided consent themselves; p < 0.0001) and a worse cognitive prognosis (day 90 MMS < 24: 15.4% and 4.8%, respectively; p < 0.002). The mortality rate was significantly higher in the surrogate consent group.CONCLUSIONS:We found that in addition to age, aphasia and stroke severity, pre-stroke cognitive status is a factor that should prompt the care team to consider requesting surrogate consent for participation in a clinical study. Given that the unfavourable outcome in patients with surrogate consent is often due to their initial clinical state (rather than inclusion in a trial per se), the issue of the family's feelings of guilt (and how to avoid these feelings) should be further addressed

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

Data from: 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 two 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 post-stroke by comprehensive neuropsychological testing, the Clinical Dementia Rating (CDR) scale, modified Rankin Scale (mRS), and Instrumental Activities of Daily Living (IADL), and analyzed using 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 using receiver operating characteristic curves. Results: In pooled analyses a baseline MoCA 2 (OR: 5.03, 95%CI: 2.20-11.51) and by IADL 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

Controlled education of patients after stroke (ceops)-nurse-led multimodal and long-term interventional program involving a patient''s caregiver to optimize secondary prevention of stroke: study protocol for a randomized controlled trial

International audienceBACKGROUND: Setting up a follow-up secondary prevention program after stroke is difficult due to motor and cognitive impairment, but necessary to prevent recurrence and improve patients' quality of life. To involve a referent nurse and a caregiver from the patient's social circle in nurse-led multimodal and long-term management of risk factors after stroke could be an advantage due to their easier access to the patient and family. The aim of this study is to compare the benefit of optimized follow up by nursing personnel from the vascular neurology department including therapeutic follow up, and an interventional program directed to the patient and a caregiving member of their social circle, as compared with typical follow up in order to develop a specific follow-up program of secondary prevention of stroke.METHODS: The design is a randomized, controlled, clinical trial conducted in the French Stroke Unit of the Strokavenir network. In total, 410 patients will be recruited and randomized in optimized follow up or usual follow up for 2 years. In both group, patients will be seen by a neurologist at 6, 12 and 24 months. The optimized follow up will include follow up by a nurse from the vascular neurology department, including therapeutic follow up, and a training program on secondary prevention directed to the patient and a caregiving member of their social circle. After discharge, a monthly telephone interview, in the first year and every 3 months in the second year, will be performed by the nurse. At 6, 12 and 24 month, the nurse will give the patient and caregiver another training session. Usual follow up is only done by the patient's general practitioner, after classical information on secondary prevention of risk factors during hospitalization. The primary outcome measure is blood pressure measured after the first year of follow up. Blood pressure will be measured by nursing personnel who do not know the group into which the patient has been randomized. Secondary endpoints are associated mortality, morbidity, recurrence, drug side-effects and medico-economic analysis.CONCLUSIONS: The result of this trial is expected to provide the benefit of a nurse-led optimized multimodal and long-term interventional program for management of risk factors after stroke, personalizing the role of the nurse and including the patient's caregiver.BACKGROUND: ClinicalTrials.gov, NCT 02132364. Registered on 7 May 2014. EUDRACT, A 00473-40

Short-term Trajectories of Poststroke Cognitive Function: A STROKOG Collaboration Study

International audienceBackground and Objectives Past studies on post-stroke cognitive function have focused on the average performance or change over time, but few have investigated patterns of cognitive trajectories after stroke. This project used latent class growth analysis (LCGA) to identify clusters of patients with similar patterns of cognition scores over the first-year post-stroke and the extent to which long-term cognitive outcome is predicted by the clusters (“trajectory groups”). Methods Data were sought from the Stroke and Cognition consortium (STROKOG). LCGA was used to identify clusters of trajectories based on standardized global cognition scores at baseline (T 1 ) and at the 1-year follow-up (T 2 ). One-step IPD meta-analysis was used to examine risk factors for trajectory groups and association of trajectory groups with cognition at the long-term follow-up (T 3 ). Results Nine hospital-based stroke cohorts with 1149 patients (63% male; mean age 66.4 years (SD=11.0)) were included. The median time assessed at T 1 was 3.6 months post-stroke, 1.0 year at T 2 and 3.2 years at T 3 . LCGA identified 3 trajectory groups, which were characterized by different mean levels of cognition scores at T 1 (low-, -3.27SD (0.94), 17%; medium-, -1.23SD (0.68), 48%; and high-performance, 0.71SD (0.77), 35%). There was significant improvement in cognition for the high-performance group (0.22 SD/year, 95% CI 0.07, 0.36), but changes for the low and medium performance groups were not significant (-0.10 SD/year, 95% CI -0.33, 0.13; 0.11 SD/year, 95% CI -0.08, 0.24 respectively). Factors associated with the low- (versus high-) performance group include age (relative risk ratio [RRR] 1.18, 95% CI 1.14, 1.23), years of education (RRR 0.61, 95% CI 0.56, 0.67), diabetes (RRR 3.78, 95% CI 2.08, 6.88), large artery versus small vessel strokes (RRR 2.77, 95% CI 1.32, 5.83), and moderate/severe strokes (RRR 3.17, 95% 1.42, 7.08). Trajectory groups were predictive of global cognition at T 3 , but its predictive power was comparable to scores at T 1 . Conclusion The trajectory of cognitive function over the first-year post-stroke is heterogenous. Baseline cognitive function ∼3.6 months post-stroke is a good predictor of long-term cognitive outcome. Older age, lower levels of education, diabetes, large artery strokes, and greater stroke severity are risk factors for lower cognitive performance over the first year