Abstract
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) (P(interaction) = .63). The APOE ε3/ε4 genotype was associated with a higher rate of decline with age (P(interaction) = .021), while the APOE ε2/ε4 genotype (P(interaction) = .016) and the APOE ε2/ε3 genotype (P(interaction) = .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 67:734-740, 2019.