Amyloid-beta relates to default and attention network connectivity during working memory retrieval

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ID: 321330
2026
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Abstract
Abstract As one of the earliest pathological events in Alzheimer’s disease, amyloid-beta accumulation has been linked to alterations in large-scale brain networks, especially the default mode network. While most prior work has focused on resting-state functional connectivity or task-evoked activation, how amyloid-beta relates to task-modulated connectivity that directly supports behavior is less explored. Here, we examined the relationship between amyloid-beta burden and task-modulated connectivity during a Letter Sternberg verbal working-memory task in eighty-four cognitively normal older adults from an ongoing longitudinal cohort (age 56-71 years; 41 female). To further understand these connectivity alterations, we tested whether these connections were associated with task performance or with cognitive reserve proxies. We found that higher amyloid-beta burden was associated with reduced connectivity -- specifically during the probe phase of working-memory retrieval. At the regional scale, lower node strength in posterior-medial regions of the default mode network was related to worse task performance and mediated the amyloid-behavior relationship. At the network scale, altered coupling between the default mode and dorsal attention networks was related to task performance but did not mediate the amyloid-behavior relationship. Moreover, physical activity was associated with network-level coupling but not with regional node strength. These findings suggest that amyloid-beta burden disrupts retrieval-related working-memory systems, particularly regions of the default mode network, while coupling between the default mode and dorsal attention networks is related to physical activity, a cognitive reserve proxy. Collectively, task-modulated connectivity provides insight into pathways through which early Alzheimer’s disease pathology influences working-memory performance and may inform targeted lifestyle or neuromodulation interventions for older adults.
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openalex_W7168535400 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hengda He, Christian Habeck, Yaakov Stern
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Journal Brain communications
Year 2026
DOI
10.1093/braincomms/fcag278
URL
https://doi.org/10.1093/braincomms/fcag278
Keywords Keywords not found

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