Nonstroke cardiovascular disease and risk of Alzheimer disease and dementia.

Unresolved issues in dementia research include (1) the association between nonstroke cardiovascular disease (CVD) and Alzheimer disease (AD) and (2) whether the association between CVD and dementia is mediated by familial factors (ie, genes and early life environment). We therefore conducted a study with both a longitudinal and a co-twin control design in 2214 Swedish twins with clinical dementia evaluation and apolipoprotein E (ApoE) genotyping. The analyses were then replicated in a register-based cohort of 18,405 individuals. Results show that CVD increases the risk of AD in carriers (but not noncarriers) of the ApoE4 allele (hazard ratio 2.39, 95% confidence interval 1.15-4.96). CVD was also associated with an almost 2-fold increased risk of developing late-life dementia (hazard ratio 1.83, 95% confidence interval 1.23-2.72). Within twin pairs, the dementia-affected twin was more likely to have had CVD than the nondemented twin partner (odds ratio 1.86, 95% confidence interval 1.11-3.13). In conclusion, this study shows that (1) nonstroke CVD increases the risk of late-life dementia but that it is only a risk factor for AD in carriers of the ApoE4 allele and (2) the association between CVD and dementia is not explained by genetic or early life environmental factors in common to both disorders.