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

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To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample.


Longitudinal study of 18 years' duration.


Biracial urban US population sample.


There were a total of 5807 participants, 60% African American (AA) and 40% European American (EA).


A composite cognitive function based on individual tests of episodic memory, perceptual speed, and the Mini-Mental State Examination.


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.


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.

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