Communication Sciences & Disorders Faculty Publications

Document Type

Article

Publication Date

7-1-2026

Abstract

Physical inactivity is a key modifiable risk factor for Alzheimer's disease (AD). However, emerging evidence suggests a bidirectional relationship where inactivity also serves as an early manifestation of AD pathology. This perspective synthesizes recent findings from long-term epidemiological cohorts, brainstem neuropathology, and digital phenotyping to reconceptualize the role of inactivity in preclinical AD. Early tau accumulation in catecholaminergic nuclei (locus coeruleus and ventral tegmental area) disrupts circuits essential for reward valuation and effort calculation. We hypothesize that this neurobiological failure may manifest as prodromal apathy and declining physical activity years before cognitive impairment. Standard metrics like step counts fail to capture these nuances. We propose a multidimensional digital phenotype – incorporating temporal complexity, circadian rhythms, and life-space mobility – to distinguish “behavioral” from “biologically constrained” inactivity. This framework has critical implications for trial enrichment and the design of personalized lifestyle interventions.

Comments

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2026 The Author(s). Alzheimer’s & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Publication Title

Alzheimer's & Dementia: Translational Research & Clinical Interventions

DOI

https://doi.org/10.1002/trc2.70316

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