Lack of effect of the apolipoprotein E ε4 genotype on cognition during healthy aging

Background: The apolipoprotein E (APOE) epsilon 4 genotype is associated with an increased risk of Alzheimer's disease. In community surveys, older adults with this genotype have been found to have lower scores on neuropsychological tests than those who do not. It is possible that this is the consequence of subclinical changes in cognition in those persons who later develop dementia. The aim of this research was to determine whether the effect of APOE genotype on cognition would remain if those who subsequently became demented were retrospectively removed from the analysis of the baseline test data from a sample of healthy adults. Method: A sample of 241 nondemented persons over the age of 65 for whom APOE genotyping was available were administered a range of neuropsychological tests at baseline and were followed up 10 years later. Results: Significant differences between the epsilon 4-present and epsilon 4-absent groups were found for the delayed recall trial of the Rey Auditory Verbal Learning Test and the Trail Making Test. When those participants known to have developed dementia during the follow-up period were excluded from the analysis of the baseline data these differences disappeared. A total of 113 nondemented survivors from the original sample were retested, and no difference was found in the rate of decline on any measure between the epsilon 4-present and epsilon 4-absent groups. Conclusions: It is likely that the reported effect of the epsilon 4 APOE genotype on cognition is the consequence of the epsilon 4-present group containing persons whose cognition is subtly affected by the early stages of a dementing process. It is also unlikely that the presence of the epsilon 4 allele by itself leads to a significantly accelerated rate of cognitive decline in the nondemented elderly.