Increasing physical activity between the ages of 45 and 65 may help prevent Alzheimer’s disease, while a sedentary lifestyle could accelerate brain changes linked to the condition, according to a new study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The findings underscore the importance of promoting exercise as a preventive public health strategy for cognitive decline.
The research, led by the Barcelona Institute for Global Health (ISGlobal) and the Barcelonaβeta Brain Research Center (BBRC)—a research center of the Pasqual Maragall Foundation—found that participants who increased their physical activity during midlife had fewer signs of Alzheimer’s-related brain pathology. The study was carried out within the ALFA (Alzheimer’s and Families) cohort and supported by the ”la Caixa” Foundation.
Globally, physical inactivity is believed to contribute to 13% of Alzheimer’s cases. The World Health Organization recommends 150 to 300 minutes of moderate activity—or 75 to 150 minutes of vigorous activity—each week to support overall health.
While earlier studies have linked exercise to improved cardiovascular and mental health, this research adds growing evidence that physical activity may directly influence brain structure and the accumulation of toxic proteins associated with Alzheimer’s disease.
“We followed middle-aged individuals in Catalonia with a family history of Alzheimer’s over a four-year period,” said Müge Akıncı, lead author and doctoral researcher at ISGlobal and BBRC at the time of the study. “Using physical activity questionnaires and neuroimaging, we assessed how changes in physical activity affected brain structure and function.”
Participants were grouped as adherent (meeting WHO physical activity guidelines), non-adherent (below recommended levels), or sedentary (no activity). Those who increased their activity levels during the study period exhibited significantly less buildup of beta-amyloid—a toxic protein that interferes with communication between neurons and is considered an early hallmark of Alzheimer’s disease.
The researchers also found a positive association between physical activity and cortical thickness, especially in the medial temporal lobe, a brain region critical for memory. Thinning in this area is among the earliest signs of neurodegeneration.
“Even those who didn’t meet the full recommendations but increased their activity somewhat showed benefits,” said Akıncı. “This suggests that any amount of physical activity—even below WHO-recommended levels—is better than none.”
Interestingly, the benefits appeared to be dose-dependent. The more participants increased their activity over time, the lower their amyloid burden and the more robust their brain structure.
“These findings reinforce the importance of promoting physical activity in middle age as a public health strategy for Alzheimer’s prevention,” said Eider Arenaza-Urquijo, lead investigator of the study. “Rather than simply urging people to meet a specific target, encouraging any increase in activity—especially for those who are inactive—may be key to reducing the risk of Alzheimer’s disease in the years ahead.”
Reference
Akıncı, M., Aguilar-Dominguez, P., Palpatzis, E., Shekari, M., Garcia-Prat, M., Deulofeu, C., Fauria, K., Garcia-Aymerich, J., Domingo Gispert, J., Suarez-Calvet, M., Grau-Rivera, O., Sánchez-Benavides, G., & Arenaza-Urquijo, E. M. (2025). Physical activity changes during midlife link to brain integrity and amyloid burden. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 2025.
