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◆ Nature Medicine2025-11-03· Medicine

Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease

Wai‐Ying Wendy Yau, Dylan Kirn, Jennifer S. Rabin, Michael J Properzi, Aaron P. Schultz, Zahra Shirzadi, Kailee Palmgren, Paulo Matos, Courtney Maa, Jeremy J. Pruzin, Stephanie A. Schultz, Rachel F. Buckley, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, Jasmeer P. Chhatwal

一句话结论 · In one sentence

Although no statistically significant differences in △BDNF were observed between the four modalities, these findings provide preliminary evidence that a muscular endurance-focused resistance training protocol (LsHr) may be effective in eliciting acute BDNF elevations in older adults. These results suggest that the interplay between training volume and intensity warrants further investigation. Given the exploratory nature of this study, our findings indicate that while LsHr shows potential, further research with larger cohorts is necessary to definitively establish whether training dose or specific modality configuration is the primary driver of BDNF modulation.

原始摘要(英文原文)· Original 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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