Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation

Objective. —To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). Design and Setting. —Population-based, case-control study from Rotterdam, the Netherlands, and New York City. Participants. —A total of 187 patients with dementia and stroke were compared with 507 controls similar in age and ethnic group. Main Outcome Measures. —TheAPOEallele frequencies in patients and controls; the odds ratio of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex, residency, and education; and the percent attributable risk related to theAPOEϵ4 allele. Results. —Overall, patients with dementia and stroke had a higherAPOEϵ4 allele frequency than controls. Compared withAPOEe3 homozygote individuals,APOEϵ4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), whileAPOEϵ4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated withAPOEϵ4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to theAPOEϵ4 allele among demented patients with stroke was 41% overall, 33% among those with VaD, and 44% among those with AD with CVD. Conclusion. —TheAPOEϵ4 allele is a genetic risk factor for dementia with stroke, including VaD and AD with CVD. This may imply shared genetic susceptibility to dementia associated with stroke and AD. Alternatively, the category of patients with dementia and stroke, including VaD as currently defined, may include patients with AD.