APOE genotype and cognitive change in young, middle-aged, and older adults living in the community.

We examined whether the apolipoprotein E (APOE) ε4 allele was associated with cognitive benefits in young adulthood and whether it reversed to confer cognitive deficits in later life ("antagonistic pleiotropy") in the absence of dementia-related neuropathology. We also tested whether the ε2 allele was associated with disadvantages in early adulthood but offered protection against cognitive decline in early old age. Eight-year cognitive change was assessed in 2,013 cognitively normal community-dwelling adults aged 20-24, 40-44, or 60-64 years at baseline. Although cognitive decline was associated with age, multilevel models contrasting the ε2 and ε4 alleles provided no evidence that the APOE genotype was related to cognitive change in any of the age groups. The findings suggest that in the absence of clinically salient dementia pathology, APOE ε2 and ε4 alleles do not exhibit antagonistic pleiotropy in relation to cognition between the ages of 20 and 72 years.