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

Neurobiology of Aging
Elisa SchellerS Klöppel

Abstract

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.

Citations

Jun 1, 2019·Scientific Reports·Jacqueline ZimmermannChris Butler
Apr 5, 2018·Frontiers in Aging Neuroscience·Elisa SchellerStefan Klöppel
Mar 14, 2019·Frontiers in Aging Neuroscience·Xiwu WangUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Jun 13, 2020·Scientific Reports·Nahid ZokaeiMasud Husain

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