Failing compensatory mechanisms during working memory in older apolipoprotein E-epsilon4 healthy adults.

How and when the known genetic risk allele, apolipoprotein E-epsilon4 (APOEepsilon4), confers risk to Alzheimer's disease has yet to be determined. We studied older adults and found that APOEepsilon4 carriers had greater neural activation in the medial frontal and parahippocampal gyrus during a memory task (cluster-corrected p < .01). When compared to a group of younger adults, interactive effects of age and APOEepsilon4 were found in the inferior frontal-anterior temporal region, one of the first areas to develop amyloid plaques in patients with Alzheimer's disease, and, in the posterior cingulate, one of the earliest areas to show decreased cerebral metabolism in Alzheimer's disease. Thus, abnormally high activation in fronto-temporal areas are present in both younger and older APOEepsilon4 carriers confronted with a working memory task when compared to non-APOEepsilon4 carriers. This effect, however, appears to diminish with age.