Joint effect of stroke and APOE 4 on dementia risk

Background: Although stroke and APOE 4 are independent risk factors for dementia, their combined effect remains uncertain. We assessed their joint effect on dementia risk. Methods: Subjects participated in Phases 1 and 2 of the Canadian Study of Health and Aging (CSHA). Dementia was diagnosed by consensus, and stroke was diagnosed by history or clinical examination. Analyses were first conducted among clinical participants only, and then rerun with the screening sample included as well. Results: Analyses included 949 participants from CSHA-1 and 1,413 from CSHA-2. During a median 4.6-year follow-up, 740 were included in the CSHA-1 to -2 incidence study. Among clinical participants, the highest prevalence (40.6% for CSHA-1 and 57.6% for CSHA-2) and incidence (8.4 per 100 person-years) of dementia occurred in elderly having both stroke and APOE 4; the lowest prevalence (19.8% for CSHA-1 and 23.3% for CSHA-2) and incidence (4.3 per 100 person-years) were among persons having neither. These findings held true when the screening sample was included. The adjusted hazard ratios of incident dementia, relative to elderly with neither stroke nor APOE 4, were 1.33 (95% CI 0.73 to 2.43) for stroke alone, 2.06 (95% CI 1.42 to 2.99) for APOE 4 alone, and 2.57 (95% CI 1.11 to 5.94) for both. No interaction on additive or multiplicative scales was suggested. Conclusions: The joint presence of stroke and APOE 4 was associated with a greater risk of dementia compared with absence of these two factors. The effect of stroke on dementia does not seem to be modified by APOE 4.