Brain Imaging and Behavior

, Volume 4, Issue 2, pp 177–188

Failing Compensatory Mechanisms During Working Memory in Older Apolipoprotein E-ε4 Healthy Adults


    • Geriatric Psychiatry BranchNIMH, National Institutes of Health
    • The Mind Research Network
  • Gang Chen
    • Scientific and Statistical Computing CoreNIMH, National Institutes of Health
  • Trey Sunderland
    • Geriatric Psychiatry BranchNIMH, National Institutes of Health
  • Robert M. Cohen
    • Geriatric Psychiatry BranchNIMH, National Institutes of Health
    • Department of Psychiatry and Behavioral Neurosciences and S. Mark Taper Department of ImagingCedars-Sinai Medical Center

DOI: 10.1007/s11682-010-9097-9

Cite this article as:
Filbey, F.M., Chen, G., Sunderland, T. et al. Brain Imaging and Behavior (2010) 4: 177. doi:10.1007/s11682-010-9097-9


How and when the known genetic risk allele, apolipoprotein E-ε4 (APOEε4), confers risk to Alzheimer’s disease has yet to be determined. We studied older adults and found that APOEε4 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 APOEε4 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 APOEε4 carriers confronted with a working memory task when compared to non-APOEε4 carriers. This effect, however, appears to diminish with age.


fMRIAPOEAlzheimer’s diseaseWorking memoryCompensation

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© Springer Science+Business Media, LLC 2010