APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging.
OBJECTIVE
To investigate whether presence of the APOE epsilon4 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.


METHODS
In a population-based sample, participants were stratified according to APOE genotype (epsilon4 or non-epsilon4) 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-epsilon4 and 26.7% of epsilon4 carriers became demented. For the 6-year period those percentages were 11.2% for non-epsilon4 carriers and 16.9% for epsilon4-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-epsilon4 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 epsilon4 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.
Bunce
D
D
Department of Psychology, Goldsmiths College, University of London, London SE14 6NW, UK. d.bunce@gold.ac.uk
Fratiglioni
L
L
Small
B J
BJ
Winblad
B
B
Bäckman
L
L
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000523:psychology*; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D012307:Risk Factors; D012494:Sampling Studies; D016037:Single-Blind Method; D013548:Sweden / Q000453:epidemiology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E