ArticleNature medicine2025
Physical activity as a modifiable risk factor in preclinical Alzheimer's disease.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanistic Investigation of Exercise Interventions in Rodent Models of Alzheimer's Disease and Prospects for Clinical Translation.Neural plasticity · 2026Pooled it
- Associations of physical fitness with brain structure, pathology and cognition in cognitively normal older adults.npj aging · 2026Article
- Microstructural Brain Reserve Moderates the Associations Between 24-h Movement Behaviors and Cognition in Older Adults: Cross-Sectional Findings From the AGUEDA Trial.Scandinavian journal of medicine & science in sports · 2026Article
- Possible Sarcopenia and Subsequent Cognitive Function in Older Chinese Adults: Limited Evidence for Mediation by Frailty.Geriatrics & gerontology international · 2026Observational
- Brain health strategies in middle-aged individuals with mild neurocognitive disorder: a scoping review.The journal of prevention of Alzheimer's disease · 2026Review
- Long-Term Physical Activity Patterns and Risk of Future Frailty: A Systematic Review and Age-Stratified Meta-Analysis.Geriatrics (Basel, Switzerland) · 2026Review
- Prospective study on physical activity and Alzheimer's disease-related biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Wearables as personal health custodians.Nature medicine · 2026Article
- A multi-organ spatial metabolomic atlas of exercising mice reveals neuronal Complex I as a convergent and sufficient axis for tau pathology reduction in PS19.bioRxiv : the preprint server for biology · 2026Article
- Combined effects of tactile stimulation and aerobic exercise on BDNF-related pathways and neurofunctional outcomes in an early-stage 5xFAD mouse model of Alzheimer's disease.Scientific reports · 2026Article
- APOE ε4 and amyloid status moderate the associations between sleep, physical activity, and tau-PET burden in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Interaction of moderate-to-vigorous physical activity and brain amyloid accumulation on longitudinal cognitive change.GeroScience · 2026Article
- Willingness and barriers to blood-based biomarker testing of Alzheimer's disease in the general population in the Czech Republic.Alzheimer's research & therapy · 2026Article
- Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review).International journal of molecular medicine · 2026Review
- Is Alzheimer's an Autoimmune Disease?Molecular neurobiology · 2026Review
- Amyloid-beta relates to default and attention network connectivity during working memory retrieval.Brain communications · 2026Article
- Exercise-conditioned extracellular vesicles in Alzheimer's disease: a multi-organ signaling network linking peripheral adaptation to brain pathology.Frontiers in immunology · 2026Review
- Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Physical inactivity is a recognized modifiable risk factor for Alzheimer's disease (AD), yet its relationship with progression of AD pathology in humans remains unclear, limiting the effective translation into prevention trials. Using pedometer-measured step counts in cognitively unimpaired older adults, we demonstrated an association between higher physical activity and slower cognitive and functional decline in individuals with elevated baseline amyloid. Importantly, this beneficial association was not related to lower amyloid burden at baseline or longitudinally. Instead, higher physical activity was associated with slower amyloid-related inferior temporal tau accumulation, which significantly mediated the association with slower cognitive decline. Dose-response analyses further revealed a curvilinear relationship, where the associations with slower tau accumulation and cognitive decline reached a plateau at a moderate level of physical activity (5,001-7,500 steps per day), potentially offering a more approachable goal for older sedentary individuals. Collectively, our findings support targeting physical inactivity as an intervention to modify the trajectory of preclinical AD in future prevention trials, and further suggest that preferentially enrolling sedentary individuals with elevated amyloid may maximize the likelihood of demonstrating a protective effect of physical activity on tau accumulation and cognitive and functional decline in early AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.