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Background and Objectives: The course and pattern of cognitive decline in ischemic cerebral small vessel disease remain poorly characterized. We analyzed the trajectory pattern of cognitive decline from age 25 to 75 years in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)., Methods: We applied latent process mixed models to data obtained from patients with CADASIL who were repeatedly scored during their follow-up using 16 selected clinical scales or cognitive tests., Results: The modeled evolutions of these scores obtained from 1,243 observations in 265 patients recruited at the French National Referral Centre (50.1 years on average and 45.3% men) showed wide and heterogeneous variations in amplitude along the age-related progression of the disease. Although the Backward Digit Span remained essentially stable, a linear deterioration of scores obtained using the Symbol Digit Numbers or Number of Errors of Trail Making Test B was detected from 25 to 75 years. By contrast, the largest score changes were observed at midlife using the Digit Cancellation Task. All other tests related to executive functions, memory performances, or global cognitive efficiency showed a rate of change accelerating especially at the advanced stage of the disease. Male gender and the presence of gait disorders or of some disability at baseline were found to predict earlier or large changes of 4 scores (Index of Sensitivity to Cueing, Delayed Total Recall, Initiation/Perseveration, and Barthel Index) in a subgroup of individuals distinct from the rest of the sample., Discussion: Cognitive alterations develop heterogeneously during the progression of CADASIL and vary largely according to the stage of the disease. These results suggest that not only the target population and study duration but also the stage of disease progression should be considered in preparing future clinical trials aimed at reducing cognitive decline in any such condition., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome., Methods: We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at p < 0.05., Results: We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816-0.986; p = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway., Conclusions: The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke., (Copyright © 2017 American Academy of Neurology.)