ABSTRACT NUMBER: ESOC2026A1190 ASSOCIATIONS OF CEREBRAL SMALL VESSEL DISEASE WITH GLOBAL AND DOMAIN SPECIFIC COGNITIVE PERFORMANCE POST-STROKE: A POOLED LONGITUDINAL ANALYSIS

Abstract Background and aims This retrospective pooled analysis evaluated the longitudinal association between total cerebral small vessel disease (CSVD) burden, its neuroimaging biomarkers, and post-stroke cognitive trajectory over three years. We sought to define the differential prognostic roles of individual CSVD markers on global and domain-specific cognition. Methods Data were analyzed from 1,376 participants (67.88% with CSVD) across two independent, prospective stroke cohorts (PROSCIS-B and INSPIRE-TMS). CSVD markers were systematically assessed on baseline MRI, these included white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), and enlarged perivascular spaces (PVS). Cognitive performance was measured annually for three years using standardized screening tools (MoCA, MMSE, or TICS). Longitudinal associations between CSVD severity (score 1-4) and cognition were assessed using mixed-effects regression models. Results CSVD severity was significantly correlated with progressive deterioration in global cognition over 3 years (ß = -0.19; p = 0.03). WMH severity emerged as an independent predictor of poorer overall cognitive performance (ß = -0.09; p < 0.01). Domain-specific analysis further revealed that lacunes were significantly associated with impaired attention performance (p = 0.02), while WMH burden correlated with diminished naming performance (p = 0.02). Conclusions These findings support the hypothesis that CSVD severity is predictive of progressive cognitive decline following ischemic stroke. Interestingly, WMH burden emerged as the strongest predictor of post-stroke cognitive decline while different CSVD MRI biomarkers seem to have differential effect on different cognitive subdomains. Taken together, these findings support the integration of MRI-based CSVD assessment for optimizing cognitive risk stratification in stroke survivors. Conflict of interest Huma Fatima Ali is a MD/PhD student in International Graduate Program of Medical Neurosciences and associated fellow at Einstein Center of Neurosciences, Charite Universitätsmedizin Berlin, Germany. Matthias Endres reports on grants from Bayer and Ipsen and fees paid to the Charité from Amgen, AstraZeneca, Bayer Healthcare, BMS, Daiichi Sankyo, all outside the submitted work. Heinrich Audebert reports on grants from Pfizer within the submitted word and fees paid from AstraZeneca, Bayer Healthcare, BMS, Boehringer Ingelheim, Novartis, Novo-Nordisk and Pfizer, all outside the submitted work.