ArticleBrain communications2026
Amyloid-beta relates to default and attention network connectivity during working memory retrieval.
Article in Brain communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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 behaviour 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 84 cognitively normal older adults from an ongoing longitudinal cohort (aged 56-71 years; 41 females). 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-behaviour 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-behaviour 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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