Longitudinal Modeling of Age-Related Memory Decline and theAPOEε4 Effect

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Abstract
The APOE ε4 allele is associated with the risk of late-onset Alzheimer's disease. The age at which memory decline diverges among persons who are homozygous for the APOE ε4 allele, those who are heterozygous for the allele, and noncarriers is unknown. Using local advertisements, we recruited cognitively normal subjects between the ages of 21 and 97 years, who were grouped according to their APOE ε4 status. We then followed the subjects with longitudinal neuropsychological testing. Anyone in whom mild cognitive impairment or dementia developed during follow-up was excluded. We compared the rates of decline in predetermined cognitive measures between carriers and noncarriers of the APOE ε4 allele, using a mixed model for longitudinal change with age. We analyzed 815 subjects: 317 APOE ε4 carriers (79 who were homozygous for the APOE ε4 allele and 238 who were heterozygous) and 498 noncarriers. Carriers, as compared with noncarriers, were generally younger (mean age, 58.0 vs. 61.4 years; PAPOE ε4 carriers diverges from that of noncarriers before the age of 60 years, despite ongoing normal clinical status.