ReviewNeurology international2026
The Role of Brain Frailty in Stroke Outcomes: A Systematic Review.
Review in Neurology international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Authors and funding
10 authors.
Funding
Abstract
BACKGROUND AND
objectivesCerebrovascular strokes and transient ischemic attacks (TIAs) remain leading causes of global mortality and long-term disability. Emerging evidence suggests that pre-existing structural brain frailty-driven by chronic cerebral small vessel disease (CSVD)-critically limits neuroplastic compensation and determines overall recovery potential. This systematic review aims to synthesize current evidence evaluating brain frailty as an independent determinant of functional and cognitive outcomes.
methodsFollowing PRISMA and Cochrane SWiM guidelines, a comprehensive literature search was conducted across PubMed, Web of Science, Embase, and Scopus. Methodological quality was evaluated using the Newcastle-Ottawa Scale (NOS). Due to anticipated clinical and methodological heterogeneity, data were synthesized via a structured narrative approach. A total of 15 studies comprising more than 18,000 participants met the inclusion criteria, including prospective cohorts, retrospective cohorts, registry analyses, pooled cohort studies, and post hoc analyses of randomized controlled trials.
resultsStructural disconnection burden emerged as one of the strongest predictors of post-stroke cognitive impairment, demonstrating remarkably large effect sizes at both 6 months (OR 9.96, 95% CI 2.21-52.40) and 36 months (OR 12.27, 95% CI 2.80-63.40). Additionally, blood-brain barrier (BBB) leakage was significantly associated with longitudinal cognitive decline (β -3.62 to -0.16,
conclusionsBrain frailty should be integrated into clinical prognostic frameworks as a key marker for predicting long-term cognitive function and functional independence in stroke patients. However, the substantial methodological and clinical heterogeneity observed across the included literature must be acknowledged as a key limitation of the current evidence base. Large-scale, prospective, multicenter longitudinal studies are required to better standardize brain frailty metrics and validate their utility in clinical practice.
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