APOLIPOPROTEIN-E EPSILON-4 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 eit her vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). Design and Setting.-Population-based, case-cont rol study from Rotterdam, the Netherlands, and New York City. Particip ants.-A total of 187 patients with dementia and stroke were compared w ith 507 controls similar in age and ethnic group. Main Outcome Measure s.-The APOE allele frequencies in patients and controls; the odds rati o of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex , residency, and education; and the percent attributable risk related to the APOE epsilon 4 allele. Results.-Overall, patients with dementia and stroke had a higher APOE epsilon 4 allele frequency than controls . Compared with APOE epsilon 3 homozygote individuals, APOE epsilon 4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6. 9; 95% CI, 1.6-29.4), while APOE epsilon 4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated wi th APOE epsilon 4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to th e APOE epsilon 4 allele among demented patients with stroke was 41% ov erall, 33% among those with VaD, and 44% among those with AD with CVD. Conclusion.-The APOE epsilon 4 allele is a genetic risk factor for de mentia with stroke, including VaD and AD with CVD. This may imply shar ed genetic susceptibility to dementia associated with stroke and AD. A lternatively, the category of patients with dementia and stroke, inclu ding VaD as currently defined, may include patients with AD.