Abstract
BACKGROUND: The APOE epsilon4 allele is an established risk factor for Alzheimer's disease, but reports of its association with vascular dementia (VaD) have been inconsistent. We examined the relationship between APOE epsilon4 allele and the risk of incident VaD in a large, population-based cohort of elderly adults with up to 10 years of follow-up between 1995 and 2005. METHODS: A total of 3,424 elderly men and women free of dementia were genotyped at the baseline assessment. Incident VaD was identified through standardized procedures administered at 3 follow-up assessments. Cox proportional hazards models were used to evaluate the risk of VaD associated with APOE epsilon4. RESULTS: The adjusted hazard ratio was 1.6 for the participants with 1 APOE epsilon4 allele (95% CI: 0.9-2.7; p = 0.083) and 4.4 for those with 2 APOE epsilon4 alleles (95% CI: 1.6-12.5; p = 0.005). The increased risk did not appear to be mediated by vascular risk factors. CONCLUSIONS: The APOE epsilon4 allele is associated with an increased risk of VaD in a dose-dependent fashion and accounts for almost 20% of VaD in the population.