APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging

Abstract

Objectives: To investigate whether presence of the apolipoprotein E (APOE) ε4 allele is related to the pathological progression of preclinical Alzheimer’s disease (AD), as reflected by change in Mini-Mental State Examination (MMSE) scores among persons in the preclinical phase of AD, and cognitively intact adults confirmed as dementia-free during the six-year assessment period.

Method: In a population-based sample, participants were stratified according to APOE genotype (ε4 or non-ε4) and whether they received a diagnosis of AD at the end of either a three- or six-year assessment period. Participants were aged 75 years and older, and were non-demented at baseline. At the end of the three-year period, 17.2% of non-ε4, and 26.7% of ε4 carriers became demented. For the six-year period those percentages were 11.2% for non-ε4 carriers, and 16.9% for ε4-carriers.

Results: Individuals in the preclinical phase of AD showed greater decline on the MMSE as compared to non-demented adults. However, the decline was most marked in the three years prior to clinical diagnosis. Further, APOE-ε4 genotype did not modify the rate of decline among to-be-demented participants, as well as individuals who would remain free of AD.

Conclusions: Although possession of the APOE ε4 allele is a risk factor for AD in old age, it does not modify the progression of the disease during the preclinical period. Further, in the absence of preclinical dementia, APOE did not influence global cognitive change in non-demented persons.