Apolipoprotein E Genotypes, Age, Race, and Cognitive Decline in a Population Sample

Kumar Rajan, Lisa L. Barnes, Robert S. Wilson, Jennifer Weuve, Elizabeth A. McAninch, Denis A. Evans

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3 Scopus citations


OBJECTIVES: To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample. DESIGN: Longitudinal study of 18 years’ duration. SETTING: Biracial urban US population sample. PARTICIPANTS: There were a total of 5807 participants, 60% African American (AA) and 40% European American (EA). MEASUREMENTS: A composite cognitive function based on individual tests of episodic memory, perceptual speed, and the Mini-Mental State Examination. RESULTS: The frequencies of APOE ε2/ε3 (14% vs 12%), ε2/ε4 (4% vs 2%), ε3/ε4 (29% vs 22%), and ε4/ε4 (4% vs 2%) genotypes were higher among AAs than EAs. After adjusting for demographic factors, the rate of decline in global cognition was twice as high among participants with the APOE ε4/ε4 genotype compared to participants with the APOE ε3/ε3 genotype (0.097 vs 0.048 SD units [SDUs] per year; P <.0001). This doubling was not different between AAs (0.091 vs 0.045 SDUs per year) and EAs (0.118 vs 0.059 SDUs per year) (Pinteraction =.63). The APOE ε3/ε4 genotype was associated with a higher rate of decline with age (Pinteraction =.021), while the APOE ε2/ε4 genotype (Pinteraction =.016) and the APOE ε2/ε3 genotype (Pinteraction =.043) were associated with a lower rate of decline with higher age. The APOE ε2/ε2 genotype was associated with a lower rate of decline in episodic memory, while the APOE ε2/ε4 was associated with a higher rate of decline in episodic memory and perceptual speed. CONCLUSIONS: The association of the APOE genotypes with cognitive decline was not different between AAs and EAs. However, individuals with different APOE genotypes showed a lower or a higher rate of decline with age. J Am Geriatr Soc, 1–7, 2018.

Original languageEnglish (US)
JournalJournal of the American Geriatrics Society
StateAccepted/In press - Jan 1 2018



  • APOE genotypes
  • cognitive decline
  • minority aging

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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