ABSTRACT NUMBER: ESOC2026A652 BRAIN PERIVASCULAR SPACES, AN EARLY MRI MARKER OF ADVERSE VASCULAR HEALTH, INCREASE FUTURE STROKE AND DEMENTIA RISK: A STUDY IN 69,378 UK BIOBANK PARTICIPANTS

Abstract Background and aims Perivascular spaces (PVS), visible on MRI, may indicate impaired microvascular health, but their relation to future stroke, cognitive decline or dementia, and variation by brain region, is unclear. We analyzed UK Biobank, a large prospective population-based study. Methods We derived PVS volumes, count, length, and width, in basal ganglia (BG) and centrum semiovale (CSO), and using T1-weighted MRI and optimal analysis algorithms (available at doi.org/10.7488/ds/7486). We express PVS measures normalized to the BG/CSO volume-of-interest. We extracted health and socioeconomic risk factors, cognitive test scores, incident stroke and dementia, from Biobank-collected and health registry-linked data. We assessed PVS and incident stroke or dementia with Cox regression, adjusted for age, white matter hyperintensities, vascular and socioeconomic risk. Results We obtained PVS measures from 69,378 participants, median age 65 (range 44-85 years), 48% male. During mean 10.5+/-SD2.7 years’ follow-up, there were (incident) 315 strokes (all-cause) and 131 dementias. Increased BG and CSO PVS volumes predicted incident stroke, (respectively hazard ratio (HR) 1.32, 95%CI 1.14,1.5, P < 0.0001; HR 1.30, 95%CI 1.13,1.5, P < 0.0001) and dementia, (respectively HR 1.57, 95%CI 1.28,1.92, P < 0.0001; HR 1.34, 95%CI 1.09,1.64, P = 0.004), per 1%-point increase in normalized PVS volume. Results were similar for PVS count, length and across cognitive domains. Conclusions Increased BG and CSO PVS indicate substantial independent increased 10-year future risk for stroke and dementia in population-based participants. Prominent PVS may provide an early risk marker for stroke/dementia, perhaps offering a “window” when early intervention(s) may be most effective. Conflict of interest John McFadden, Roberto Duarte Coello, Maria Valdes-Hernandez, Francesca Chappell, Joanna Wardlaw receive research grants from Dementia Platform UK, The Hilary and Galen Weston Foundation, UK Dementia Research Institute, Row Fogo Charitable Trust that funded the work; Joanna Wardlaw advises IXICO Company.