A-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease

Objective:As the absence of A-related memory decline in APOE epsilon 4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize A-related cognitive decline over 72 months in APOE epsilon 4 carriers and noncarriers who were cognitively normal (CN).Methods:CN older adults (n = 423) underwent A imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments.Results:Relative to A- CN epsilon 4 noncarriers, both A+ CN epsilon 4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in A+ CN epsilon 4 carriers than in A+ CN epsilon 4 noncarriers. No cognitive decline was evident in A- CN epsilon 4 carriers.Conclusions:In CN older adults, A+ is associated with memory decline in epsilon 4 noncarriers; however, the rate of this decline is much slower than that observed in epsilon 4 carriers. These data indicate that the processes by which epsilon 4 carriage increases the rate of A-related cognitive decline occur in the preclinical stage of Alzheimer disease.