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Abstract
Objective: To investigate whether presence of the APOE ε4 allele is related to the pathologic progression of preclinical Alzheimer 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 6-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 3- or 6-year assessment period. Participants were aged 75 years and older, and were nondemented at baseline. At the end of the 3-year period, 17.2% of non-ε4 and 26.7% of ε4 carriers became demented. For the 6-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 nondemented adults. However, the decline was most marked in the 3 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 nondemented persons.
- Received March 28, 2003.
- Accepted April 28, 2004.
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