Effects of APOE on cognitive aging in community-dwelling older adults

Abstract

Objective: The apolipoprotein E (APOE) gene is an established risk factor for sporadic Alzheimer's disease, with elevated risk for ϵ4-carriers and reduced risk for ϵ2-carriers. However, it is unclear whether APOE modifies risk for cognitive decline in normal aging. The objective of this study was to determine whether ϵ2 and ϵ4 are associated with rates of normal cognitive aging, and whether associations of ϵ4 with cognitive decline are modified by sex, education or health behaviors (exercise, alcohol consumption, smoking). Method: A community-based sample of 1,393 older adults were genotyped for APOE and underwent cognitive assessment up to seven times over a maximum of period of 27 years. Results: ϵ2-carriers showed slower executive function decline with age relative to ϵ3 homozygotes or ϵ4-carriers, whereas ϵ4-carriers demonstrated more rapid executive function and verbal fluency decline. Accelerated executive function decline was particularly pronounced in ϵ4-carriers with lower education. After excluding individuals with cognitive impairment, faster executive function decline was still apparent in ϵ4-carriers, and the effect of ϵ4 on episodic memory interacted with alcohol consumption, such that only ϵ4-carriers who did not drink showed more rapid memory decline than ϵ4 noncarriers. The influence of ϵ4 on cognitive aging did not differ by sex, nor was it modified by smoking or exercise. Conclusions: These findings indicate that the ϵ2 and ϵ4 alleles have differential effects on cognitive aging, and that negative effects of ϵ4 may be partly mitigated by behavioral choices.