This simple daily habit could delay Alzheimer’s symptoms by years

A new study suggests that for older adults with early signs of Alzheimer’s disease in their brains, moderate physical activity is associated with a slower rate of cognitive decline. The research, published in Nature Medicine, indicates that this benefit appears to stem not from reducing the initial protein plaques linked to the disease, but from slowing the accumulation of a second protein, tau, which is more directly tied to memory loss.

Alzheimer’s disease is characterized by the buildup of two main proteins in the brain. The first, amyloid-beta, forms clumps called plaques that can appear decades before any symptoms emerge. The second protein, tau, later forms tangles inside brain cells, a development that tracks closely with the onset of memory and thinking problems.

While physical inactivity is a known modifiable risk factor for Alzheimer’s, the specific ways it affects this biological progression in humans have remained somewhat unclear. Many previous studies relied on self-reported exercise, which can be prone to inaccuracies, especially in people who may be experiencing early cognitive changes.

To get a more precise picture, a team of researchers at Mass General Brigham and Harvard Medical School utilized data from the Harvard Aging Brain Study. This long-term project follows older adults to better understand brain aging and Alzheimer’s disease. The researchers sought to use objective measurements to connect physical activity with the specific brain changes and cognitive symptoms seen in the disease’s preclinical stage, the long period when brain changes are underway but before dementia is apparent.

The investigation involved 296 participants between the ages of 50 and 90, all of whom were cognitively healthy at the study’s outset. To measure their physical activity, each participant wore a waistband-mounted pedometer for seven consecutive days to calculate an average daily step count.

The researchers also used positron emission tomography, or PET scans, to measure the amount of amyloid-beta plaques in each person’s brain at the beginning of the study. Over a follow-up period that lasted up to 14 years, with an average of over nine years, participants received annual cognitive assessments to track any changes in their thinking and memory skills. A smaller group of 172 participants also received repeated PET scans to monitor the accumulation of tau tangles over time.

The analysis revealed a clear pattern among individuals who had elevated levels of amyloid-beta in their brains at the start. In this at-risk group, those who took more steps per day experienced significantly slower declines on cognitive tests. They also showed slower declines in their ability to perform daily functions. This relationship between physical activity and better cognitive outcomes was not observed in people who had low levels of amyloid at baseline, largely because that group experienced very little cognitive decline over the study period.

To understand the mechanism behind this protective association, the researchers first checked whether physical activity was linked to the amount of amyloid itself. They found no connection. People who were more active did not have less amyloid at the beginning of the study, nor did they accumulate it more slowly over time.

The key difference appeared to be related to tau. In participants with high amyloid levels, taking more steps per day was associated with a slower buildup of tau tangles in the inferior temporal cortex, a brain region affected early in Alzheimer’s disease.

“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 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.”

Further statistical modeling suggested that this effect on tau was the primary reason for the cognitive benefits. The analysis indicated that the slower accumulation of tau fully accounted for the relationship between physical activity and slower cognitive decline. It also partially explained the link between activity and slower functional decline.

“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, 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.”

The study also examined how much activity was needed to see a benefit. The researchers categorized participants into four groups based on their daily step counts: inactive (3,000 steps or fewer), low activity (3,001 to 5,000 steps), moderate activity (5,001 to 7,500 steps), and active (more than 7,501 steps). They found that even moving from the inactive group to the low-activity group was associated with substantially slower tau buildup and cognitive decline.

The benefits continued to increase into the moderate-activity range but then appeared to level off, suggesting that the largest gains were seen when sedentary individuals became more active. This may offer a more approachable goal than the popular 10,000-steps-a-day target.

“We want to empower people to protect their brain and cognitive health by keeping physically active,” said first-author Wai-Ying Wendy Yau, 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.”

As an observational study, this research identifies strong associations but cannot definitively prove cause and effect. It is possible that individuals with the very earliest, subtle brain changes of preclinical Alzheimer’s were already becoming less physically active, a concept known as reverse causality.

The researchers conducted several sensitivity analyses to account for this possibility, and their results remained consistent. The study population was also primarily composed of highly educated, non-Hispanic white individuals, which means the findings might not be generalizable to all populations.

Looking ahead, the research team plans to explore which aspects of physical activity, such as intensity or consistency, might be most important for brain health. They also intend to investigate the biological mechanisms that could connect physical activity to reduced tau accumulation. The results of this study could help in designing future clinical trials that test exercise interventions, especially by suggesting that enrolling sedentary individuals who have elevated brain amyloid may be the best way to detect a protective effect.

The study, “Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease,” was authored by Wai-Ying Wendy Yau, Dylan R. Kirn, Jennifer S. Rabin, Michael J. Properzi, Aaron P. Schultz, Zahra Shirzadi, Kailee Palmgren, Paola Matos, Courtney Maa, Jeremy J. Pruzin, Stephanie A. Schultz, Rachel F. Buckley, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, and Jasmeer P. Chhatwal.