APOE moderates compensatory recruitment of neuronal resources during working memory processing in healthy older adults.

Scheller, Elisa; Peter, Jessica; Schumacher, Lena V; Lahr, Jacob; Mader, Irina; Kaller, Christoph P; Klöppel, Stefan (2017). APOE moderates compensatory recruitment of neuronal resources during working memory processing in healthy older adults. Neurobiology of aging, 56, pp. 127-137. Elsevier 10.1016/j.neurobiolaging.2017.04.015

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The APOE ε4 allele increases the risk for sporadic Alzheimer's disease and modifies brain activation patterns of numerous cognitive domains. We assessed cognitively intact older adults with a letter n-back task to determine if previously observed increases in ε4 carriers' working-memory-related brain activation are compensatory such that they serve to maintain working memory function. Using multiple regression models, we identified interactions of APOE variant and age in bilateral hippocampus independently from task performance: ε4 carriers only showed a decrease in activation with increasing age, suggesting high sensitivity of fMRI data for detecting changes in Alzheimer's disease-relevant brain areas before cognitive decline. Moreover, we identified ε4 carriers to show higher activations in task-negative medial and task-positive inferior frontal areas along with better performance under high working memory load relative to non-ε4 carriers. The increased frontal recruitment is compatible with models of neuronal compensation, extends on existing evidence, and suggests that ε4 carriers require additional neuronal resources to successfully perform a demanding working memory task.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > University Psychiatric Services > University Hospital of Geriatric Psychiatry and Psychotherapy

UniBE Contributor:

Peter, Jessica, Klöppel, Stefan


600 Technology > 610 Medicine & health








Katharina Klink

Date Deposited:

15 Sep 2017 10:02

Last Modified:

05 Dec 2022 15:06

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

APOE Aging Functional magnetic resonance imaging Moderator analysis Multiple regression Neuronal compensation Working memory





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