Abstract
Objective: To assess risk of dementia after first-ever hemorrhagic or ischemic strokes in three prospective cohort studies (Three City, Framingham Heart Study and Rotterdam Study). Methods: Prospective data on incident hemorrhagic or ischemic strokes and matched stroke free comparison was used for each stroke subtype. 5-year risk of dementia after hemorrhagic or ischemic stroke was assessed using a matched case-cohort design. A random effects meta-analysis was used to combine hazard ratios for each study and variations in risk stratified by APOE ε4 allele were assessed. A direct comparison of risk of dementia after hemorrhagic compared with ischemic strokes was evaluated. In a sensitivity analysis Fine & Gray models were conducted after adjusting for competing deaths and subdistribution hazard ratios were computed. Pre-event and post-event cumulative incidence of dementia at 3, 6, 12, 24, 36 and 60 months were assessed. Results: A total of 4,922 persons, including 247 incident hemorrhagic strokes and 1,427 ischemic strokes were included. The combined hazard ratios of dementia were 2.78 (95% CI 1.28, 6.03) after hemorrhagic and 3.35 (1.51, 7.43) after ischemic stroke compared to stroke free individuals. The combined risk of dementia was 0.71 (0.14, 3.68) after hemorrhagic compared with ischemic stroke. Among individuals with APOE ε4 allele, the risk of dementia was 3.88 (1.16, 12.98) after hemorrhagic stroke and 2.10 (1.28, 3.42) after ischemic stroke compared to stroke-free individuals. The cumulative incidence post-event for hemorrhagic strokes flattened between 6 and 24 months with slight increase thereafter, in-contrast to a steady increase in dementia risk over time after ischemic strokes. Conclusions: No difference was observed in overall 5-year risk of dementia after hemorrhagic or ischemic stroke, while the risk was about 3 times higher compared to stroke-free individuals of similar risk profiles. APOE ε4 allele doubles the risk of dementia among hemorrhagic stroke survivors. Risk of dementia after ischemic stroke follows a stepwise pattern overtime, in contrast, dementia risk after hemorrhagic stroke is highest in the early phase.
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