Apolipoprotein E and cognitive change in an elderly population

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Abstract
The apolipoprotein E (apoE) ε4 allele is overrepresented, and the apoE ε2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population‐based sample of 1,899 individuals 65 years and older as a follow‐up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE ε4 and apoE ε2 in predicting performance on a delayed recall task over a 4‐ to 7‐year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE ε4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE ε2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE ε4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impairment despite inheritance of one or two apoE ε4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.