Walking may be the brain’s best defense against Alzheimer’s

On average, people who walked between 3,000 and 5,000 steps a day experienced about three years of delay in cognitive decline. Those who walked 5,000 to 7,500 steps per day saw that delay extend to around seven years. In contrast, participants who were largely inactive showed faster accumulation of tau proteins in the brain, which is associated with Alzheimer's progression, and more rapid declines in thinking skills 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."

Long-Term Study on Activity and Brain Changes

Researchers examined 296 individuals aged 50 to 90 who showed no cognitive impairment at the start of the Harvard Aging Brain Study. Participants wore waistband pedometers to track physical activity and underwent PET scans to measure amyloid-beta plaques and tau tangles in the brain. They completed yearly cognitive assessments over a period ranging from two to 14 years (average = 9.3 years), and a subset received additional brain scans to monitor changes in tau over time.

The results showed that participants with elevated amyloid-beta who took more daily steps experienced slower cognitive decline and a slower buildup of tau proteins. Statistical modeling indicated that the primary benefit of physical activity came from its association with slower tau accumulation. Among participants with low amyloid-beta levels, there was little evidence of either cognitive decline or tau buildup, and no significant link to activity levels.

Building Cognitive Resilience Through Movement

"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 at Mass General Brigham 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."

The team plans to further explore which types of physical activity are most beneficial, including how intensity and long-term exercise patterns might influence brain health. They also aim to uncover the biological mechanisms that connect physical activity, tau buildup, and cognitive function. The researchers believe these insights could inform future clinical trials that test whether exercise-based interventions can slow cognitive decline in older adults, particularly those at elevated risk for Alzheimer's.

Empowering People to Take Action

"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 at Mass General Brigham. "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 and 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 listed in Nature Medicine.

Funding: This work was supported by the 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.