Increasing your steps by even a little bit may help slow down the progression of Alzheimer's disease among people at heightened risk, according to a new study. In a paper published in Nature Medicine , Mass General Brigham researchers found that physical activity was associated with slower rates of cognitive decline in older adults with elevated levels of amyloid-beta, a protein associated with Alzheimer's.
Cognitive decline was delayed by three years on average for people who walked just 3,000-5,000 steps per day, and by seven years in people who walked 5,000-7,500 steps per day. Sedentary individuals had a significantly faster buildup of tau proteins in the brain and more rapid declines in cognition and daily functioning.
"This sheds light on why some people who appear to be on an Alzheimer's disease trajectory don't decline as quickly as others," said senior author Jasmeer Chhatwal, MD, PhD , of the Mass General Brigham Department of Neurology. "Lifestyle factors appear to impact the earliest stages of Alzheimer's disease, suggesting that lifestyle changes may slow the emergence of cognitive symptoms if we act early."
The researchers analyzed data from 296 participants aged 50-90 years old in the Harvard Aging Brain Study who were all cognitively unimpaired at the beginning of the study. They used PET brain scans to measure baseline levels of amyloid-beta in plaques and tau in tangles and assessed the participants' physical activity using waistband pedometers. The participants received annual follow-up cognitive assessments for between two and 14 years (average = 9.3 years), and a subset received repeated PET scans to track changes in tau.
Higher step counts were linked to slower rates of cognitive decline and a slower buildup of tau proteins in participants with elevated baseline levels of amyloid-beta. The researchers' statistical modeling suggested that most of the physical activity benefits associated with slowing cognitive decline were driven by slower tau buildup. By contrast, in people with low baseline levels of amyloid-beta, there was very little cognitive decline or accumulation of tau proteins over time and no significant associations with physical activity.
"We are thrilled that data from the Harvard Aging Brain Study has helped the field better understand the importance of physical activity for maintaining brain health," said co-author Reisa Sperling, MD, a neurologist in the Mass General Brigham Department of Neurology and co-principal investigator of the Harvard Aging Brain Study. "These findings show us that it's possible to build cognitive resilience and resistance to tau pathology in the setting of preclinical Alzheimer's disease. This is particularly encouraging for our quest to ultimately prevent Alzheimer's disease dementia, as well as to decrease dementia due to multiple contributing factors."
Looking ahead, the researchers plan to dive deeper into which aspects of physical activity may be most important, for example exercise intensity and longitudinal activity patterns. They also plan to investigate the biological mechanisms linking physical activity, tau buildup, and cognitive health. Critically, the authors believe that this work may help design future clinical trials that test exercise interventions to slow late-life cognitive decline, especially in individuals who are at heightened risk due to preclinical Alzheimer's disease.
"We want to empower people to protect their brain and cognitive health by keeping physically active," said first-author Wai-Ying Wendy Yau, MD , a cognitive neurologist in the Mass General Brigham Department of Neurology. "Every step counts — and even small increases in daily activities can build over time to create sustained changes in habit and health."
Authorship: In addition to Yau, Chhatwal and Sperling, Mass General Brigham authors include, Dylan R. Kirn, Michael J. Properzi, Aaron P. Schultz, Zahra Shirzadi, Kailee Palmgren, Paola Matos, Courtney Maa, Stephanie A. Schultz, Rachel F. Buckley, Dorene M. Rentz, and Keith A. Johnson. Additional authors include Jennifer S. Rabin, Jeremy J. Pruzin.
Disclosures: The authors have no competing interests relevant to the current study. Potential conflicts of interest outside of the submitted work are included in Nature Medicine.
Funding: This study was funded by National Institutes of Health (K23 AG084868, K01 AG084816, P01 AG036694, K24 AG035007, R01 AG062667, R01 AG071865, P41EB015896, S10RR021110, S10RR023401, S10RR023043), the Doris Duke Charitable Foundation Clinical Scientist Development Award, and the Massachusetts Life Sciences Center.
Paper cited: Yau, W et al. "Physical Activity as a Modifiable Risk Factor in Preclinical Alzheimer's Disease" Nature Medicine DOI: 10.1038/s41591-025-03955-6
