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

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Geriatric Psychiatry Branch, NIMH, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Francesca M. Filbey, Trey Sunderland & Robert M. Cohen

  2. Scientific and Statistical Computing Core, NIMH, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Gang Chen

  3. The Mind Research Network, 1101 Yale Blvd., Albuquerque, NM, 87106, USA

    Francesca M. Filbey

  4. Department of Psychiatry and Behavioral Neurosciences and S. Mark Taper Department of Imaging, Cedars-Sinai Medical Center, 8730 Alden Dr., Los Angeles, CA, 90048, USA

    Robert M. Cohen

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  1. Francesca M. Filbey
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  2. Gang Chen
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  4. Robert M. Cohen
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Correspondence to Francesca M. Filbey.

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This work was supported by NIMH ZO1 MH00330-14

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Filbey, F.M., Chen, G., Sunderland, T. et al. Failing Compensatory Mechanisms During Working Memory in Older Apolipoprotein E-ε4 Healthy Adults. Brain Imaging and Behavior 4, 177–188 (2010). https://doi.org/10.1007/s11682-010-9097-9

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