Brain Imaging and Behavior

, Volume 4, Issue 2, pp 177–188 | Cite as

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

  • Francesca M. Filbey
  • Gang Chen
  • Trey Sunderland
  • Robert M. Cohen


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.


fMRI APOE Alzheimer’s disease Working memory Compensation 



We are grateful to Karen Putnam for managing our blind to the subjects’ genotypes. Also, thanks to Irene Dustin, NP for providing the clinical screens and to Heather Kiefer and Kelly Slack for the data collection.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Francesca M. Filbey
    • 1
    • 3
  • Gang Chen
    • 2
  • Trey Sunderland
    • 1
  • Robert M. Cohen
    • 1
    • 4
  1. 1.Geriatric Psychiatry BranchNIMH, National Institutes of HealthBethesdaUSA
  2. 2.Scientific and Statistical Computing CoreNIMH, National Institutes of HealthBethesdaUSA
  3. 3.The Mind Research NetworkAlbuquerqueUSA
  4. 4.Department of Psychiatry and Behavioral Neurosciences and S. Mark Taper Department of ImagingCedars-Sinai Medical CenterLos AngelesUSA

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