Women with poor brain health at time of ischemic stroke endure worse outcomes compared to men

ABSTRACT Importance Prognosticating functional independence after an acute stroke is critical for anticipatory guidance and rehabilitation planning. Here we demonstrate that poor brain health at the time of incident stroke is linked to worse functional outcomes for women compared to men. Objective To determine if brain health at time of stroke presentation has a differential effect on functional outcomes between men and women. Design Retrospective cross-sectional study. Setting Analysis conducted in 2025 with multi-center patient data that included participants from two large acute ischemic stroke cohorts; local (GASROS) and multinational (MRI-GENIE) between the years 2003 and 2011. Participants Clinical data collected for enrolled study participants included demographic data, medical history of hypertension, diabetes mellitus, hyperlipidemia, smoking status, acute stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS), stroke etiology, and modified Rankin Scale (mRS) score at 90 days post-stroke. Brain health was quantified as effective reserve derived from acute neuroimaging data. Exposure(s) designated sex, retrieved from registration records. Main Outcome Functional outcome was measured by mRS scores at 90 days post-stroke, in men and women with poor, moderate, or good brain health at time of stroke injury. Results A total of 1039 patients were included in the analysis, 37.8 % women, median age 67 [interquartile range 56-77]. Women with poor brain health (i.e. lowest quartile of effective reserve) had worse functional outcomes at 90 days (55.6% with mRS>2) compared to men with poor brain health (31.2% with mRS>2: p < 0.001). This difference between men and women was not observed in categories of moderate or good brain health. There was no observed significant difference in stroke severity, volume of acute lesion, burden of white matter hyperintensities, or stroke etiology between men and women with poor brain health. Conclusions and Relevance Brain health at the time of incident stroke has a differential effect on functional outcomes at 90 days between men and women. Women with poor brain health endure disproportionately worse outcomes compared to men. This highlights an important step in understanding sex-specific vulnerability in early recovery post-stroke, and can inform disposition, rehabilitation services, and resource allocation planning.