The number of daily steps associated with slower Alzheimer’s disease progression was a goal many older adults could reach, data from the Harvard Aging Brain Study suggested.

In a group of cognitively unimpaired older adults with elevated levels of amyloid-beta, Alzheimer’s-related decline was delayed by an estimated 3 years on average for those who walked 3,000-5,000 steps per day, and by 7 years in people who walked 5,000-7,500 steps per day, reported Wai-Ying Wendy Yau, MD, of Mass General Brigham in Boston, and co-authors.

This relationship emerged only for people with elevated brain amyloid. It was not related to lower amyloid burden at baseline or over time. Instead, higher physical activity was associated with slower amyloid-related inferior temporal tau accumulation, which mediated associations with slower cognitive decline, Yau and colleagues wrote in Nature Medicine.

“This sheds light on why some people who appear to be on an Alzheimer’s disease trajectory don’t decline as quickly as others,” co-author Jasmeer Chhatwal, MD, PhD, also of Mass General Brigham, said in a statement.

“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,” Chhatwal added.

Elevated brain amyloid is a potential early sign of Alzheimer’s disease, even in people who are cognitively normal.

“This research provides strong evidence that moderate levels of physical activity are associated with slower progression of the earliest stages of Alzheimer’s disease, and that this is linked to slower accumulation of tau protein, which is an important cause of brain cell loss,” wrote Charles Marshall, PhD, of Queen Mary University of London, on the U.K. Science Media Center web site.

“With this type of observational study, it is always hard to be sure whether the physical activity is actually the thing causing the observed difference,” Marshall pointed out.

“The authors do a good job of trying to disentangle this, but we cannot be certain whether the people doing more exercise are healthier in other ways, nor whether the development of Alzheimer’s disease changes are influencing activity levels (reverse causality),” Marshall continued. “We also cannot be sure that it is physical activity during this period in later life that makes the difference, or whether those who are more active now have been more active for decades and that the benefits accrue in the much longer term.”

Physical activity has been identified as a modifiable risk factor for dementia, but its relationship with Alzheimer’s pathology in humans is unclear, Yau and colleagues noted.

The analysis included data from 296 Harvard Aging Brain Study participants who were cognitively unimpaired at baseline. Waistband pedometers measured physical activity at baseline, and amyloid and tau were assessed with PET. In a subset of participants, global amyloid and inferior temporal cortex tau burdens were measured longitudinally.

Data were collected between 2010 and 2025. Participants received annual follow-up cognitive and functional evaluations using Preclinical Alzheimer’s Cognitive Composite-5 (PACC5) and Clinical Dementia Rating Sum of Boxes (CDR-SB) assessments. The median cognitive follow-up was 9.2 years.

At baseline, participants had an average age of 72 years and 30% had elevated amyloid. Most participants (59%) were women. Mean baseline steps per day were 5,719.

In participants with elevated baseline amyloid, even low levels of physical activity — 3,001-5,000 steps per day — were associated with substantially slower rates of tau accumulation, cognitive decline, and functional decline, Yau and colleagues noted. Sedentary individuals had a significantly faster tau buildup and more rapid declines in cognition and daily functioning.

An analysis of PACC5 scores estimated that participants with elevated amyloid would become cognitively impaired at 6.5 years from baseline if they were inactive, at 9.6 years if they had a low level of activity (3,001-5,000 steps), and at 13.6 years if they had a moderate physical activity level (5,001-7,500 steps). Findings were similar for CDR-SB scores.

“Notably, the associations with more favorable tau and cognitive trajectories reached a plateau by moderate levels of physical activity (5,001-7,500 steps per day), which may be a less daunting goal for sedentary older adults than the popular goal of 10,000 steps per day commonly referenced in lay media,” Yau and co-authors wrote.

The study had several limitations, the researchers acknowledged. The analysis was observational and reverse causality could not be ruled out. “Future randomized clinical trials are required to establish causal relationships,” Yau and colleagues stated.

Physical activity was assessed only once, at baseline. In addition, the sample size was small, and the cohort consisted largely of highly educated, white individuals.