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March 12, 1997

Apolipoprotein E ϵ4 and the Risk of Dementia With Stroke: A Population-Based Investigation

Author Affiliations

From the Gertrude H. Sergievsky Center (Drs Slooter, Tang, Stern, Tatemichi, and Mayeux), the Departments of Neurology (Drs Tang, Stern, Bell, Tatemichi, and Mayeux), Psychiatry (Drs Stern and Mayeux), and Pathology (Dr Tycko), and Taub Center for Alzheimer's Disease Research (Drs Stern, Tycko, and Mayeux), and the Division of Epidemiology (Dr Mayeux), School of Public Health, Columbia University, New York, NY; Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, the Netherlands (Drs Slooter, van Duijn, Ott, Breteler, and Hofman); and Neurogenetics Laboratory, Flander Interuniversity, Institute of Biotechnology, Born-Bunge Foundation and Department of Biochemistry, University of Antwerp, Antwerp, Belgium (Dr Broeckhoven).

JAMA. 1997;277(10):818-821. doi:10.1001/jama.1997.03540340052032

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.  —The APOE allele 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 the APOE ϵ4 allele.

Results.  —Overall, patients with dementia and stroke had a higher APOE ϵ4 allele frequency than controls. Compared with APOE e3 homozygote individuals, APOE ϵ4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), while APOE ϵ4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated with APOEϵ4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to the APOEϵ4 allele among demented patients with stroke was 41% overall, 33% among those with VaD, and 44% among those with AD with CVD.

Conclusion.  —The APOE ϵ4 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.

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