Association between APOE ε4 Allele and Vascular Dementia: The Cache County Study

Background: The APOE epsilon 4 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 epsilon 4 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 epsilon 4. Results: The adjusted hazard ratio was 1.6 for the participants with 1 APOE epsilon 4 allele (95% CI: 0.9-2.7; p = 0.083) and 4.4 for those with 2 APOE epsilon 4 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 epsilon 4 allele is associated with an increased risk of VaD in a dose-dependent fashion and accounts for almost 20% of VaD in the population. Copyright (C) 2010 S. Karger AG, Basel