Abstract Body: Background. With the continuous advances in AI and ADRD biomarkers’ technology, more cerebrovascular disease survivors will become eligible for inclusion in ADRD trials. Stroke survivors represent a key population at ADRD risk. Given the pathophysiology of progression to dementia after stroke, identification and assessment of risk biomarkers and ADRD therapeutic targets that are tailored for survivors of cerebrovascular disease and stroke, is critical. Owing to the required sample sizes to sufficiently detect efficacy of therapeutic targets and the rarity of some stroke subtypes, global collaborative efforts and improved study designs that would allow rigorous comparative inference from population-based cohorts to ADRD trial cohorts are essential to optimize future inclusion of stroke survivors in ADRD therapeutic trials.

Objective & Methods. To assess 5-year risk of progression to dementia following first-ever stroke with a focus on stroke subtype, early progression to dementia and APOE ε4 allele carriership among stroke survivors using an improved population-based study design for global ADRD risk and ADRD biomarker assessment. Meta-analysis of prospective population-based studies in Europe and USA (including Three City (France), Framingham Heart Study (USA) and the Rotterdam Study (Netherlands). Methods were harmonized and reproduced in identical manner across the cohorts.

Results. The study included 198 individuals with hemorrhagic stroke and 396 stroke-free matched individuals, 1,236 individuals with ischemic stroke and 2,472 stroke-free matched individuals. In the hemorrhagic stroke group compared to stroke-free individuals, the combined hazard ratio was 1.75 (95% CI 0.85, 3.60) after APOE ε4 adjustment and 2.23 (95% CI 1.13, 4.43) in the ischemic stroke group. After excluding individuals with early progression to dementia, the risk of dementia in the hemorrhagic stroke group was 2.49 (95% CI 0.89, 6.94) and 1.74 (95% CI 1.24, 2.43) in the ischemic stroke group.

Conclusion. Using an improved study design implemented in populations in Europe and the U.S.A, the present findings suggest that 5-year risk of dementia remains high following ischemic or hemorrhagic stroke and after adjustment for APOE4 carriership. These findings provide preliminary evidence support on ADRD risk and risk biomarkers in stroke survivors to optimize stroke survivors’ inclusion in future clinical trials of Alzheimer’s and Related Dementias.