Middle-aged couple walking for exercise

Living an active lifestyle can promote brain health and protect against Alzheimer's disease. (Inside Creative House/Shutterstock)

In a nutshell

  • Getting more active in midlife, even if you’ve been inactive, may help protect your brain from Alzheimer’s. People who started exercising during the study had lower levels of amyloid-beta, a hallmark of the disease.
  • Staying sedentary in your 50s and 60s was linked to thinning in brain regions vulnerable to Alzheimer’s. Even light or moderate activity was better than none at all.
  • The more participants increased their physical activity, the better their brain health appeared. This dose-dependent link suggests that every extra bit of movement may help reduce Alzheimer’s risk.

BARCELONA, Spain — Want to keep your brain healthy as you age? You might need to lace up those sneakers. A new international study has found that increasing your physical activity during midlife could significantly reduce your risk factors for Alzheimer’s disease, even if you haven’t been active before. The research offers compelling evidence that it’s never too late to start moving, and your brain will thank you.

The study, published in Alzheimer’s & Dementia, revealed that middle-aged adults who increased their physical activity showed lower levels of amyloid-beta in their brains, the sticky protein fragments that form plaques characteristic of Alzheimer’s disease. However, those who remained sedentary (with no physical activity) showed thinning in critical brain regions vulnerable to Alzheimer’s compared to their more active peers.

According to the researchers, increasing physical activity during midlife may benefit people in the earliest stages of Alzheimer’s disease. This could be extremely helpful for the millions of adults looking for practical ways to preserve their cognitive health.

The research team, based primarily in Spain, followed 337 cognitively normal middle-aged adults (average age about 60 years) over roughly four years. The participants weren’t just any group; they were individuals at increased risk of developing Alzheimer’s disease, with 86.3% having at least one parent with the condition.

Woman getting exercise at gym by running on treadmill
Even walking for exercise can help protect your brain health. (Andrea Piacquadio on Pexels)

Participants reported their physical activity levels at the beginning of the study and again at a follow-up visit about four years later. The researchers grouped people based on how their exercise habits changed—whether they stayed inactive, didn’t meet WHO guidelines, followed the guidelines, stopped following them, or started meeting them.

For context, the WHO recommends 150-300 minutes of moderate-intensity activity (like brisk walking) or 75-150 minutes of vigorous-intensity activity per week for middle-aged and older adults. That breaks down to as little as 30 minutes of moderate exercise five days a week, which is an achievable goal for many people.

During follow-up visits, participants underwent brain scans, including structural MRIs to measure brain thickness and PET scans to detect amyloid-beta buildup.

People who remained sedentary throughout the study period showed significantly lower cortical thickness in brain regions commonly affected early in Alzheimer’s disease compared to more active participants. This thinning was evident when comparing the sedentary group to those who maintained even limited physical activity, suggesting that some movement is better than none at all.

Participants who weren’t initially meeting WHO recommendations but became physically active during the study showed lower amyloid-beta burden compared to those who went in the opposite direction, starting active but becoming sedentary. This suggests that adopting an active lifestyle, even later in life, may help protect the brain.

Older man exercising and stretching outside
Physically active middle-aged adults are less likely to develop the proteins in the brain that are indicators of Alzheimer’s. (Photo by PeopleImages.com – Yuri A on Shutterstock)

The researchers also found a dose-dependent relationship between increased physical activity and lower amyloid levels. Simply put, the more participants increased their activity, the less amyloid-beta they accumulated in their brains. This relationship held true even after controlling for factors like age, sex, education, genetic risk factors, and mental health. This means that every bit of additional activity provides incremental benefits for brain health.

These findings target the earliest, “preclinical” stage of Alzheimer’s disease when changes begin occurring in the brain decades before symptoms appear. This preclinical stage represents a crucial window of opportunity for intervention, potentially preventing or delaying the eventual development of dementia.

While previous research has established connections between physical activity and reduced dementia risk, this study helps explain what is actually happening in the brain. This is concrete evidence of how physical activity might be protecting the brain.

For middle-aged adults looking to preserve their cognitive health, increasing physical activity, even to modest levels, appears to offer significant protection for the brain. Even some activity is better than none when it comes to health benefits, which aligns with current WHO guidelines.

Given that approximately 13% of Alzheimer’s cases worldwide could be attributable to physical inactivity, promoting physical activity as a key preventive strategy against Alzheimer’s disease could have a huge impact.

Alzheimer’s disease affects millions worldwide, and no current cure is available. Evidence-based prevention strategies, such as increased physical activity, offer a promising pathway for reducing the global burden of this devastating condition. In the fight against Alzheimer’s disease, getting active might be as important as your genes.

Paper Summary

Methodology

The study included 337 cognitively unimpaired middle-aged adults from the ALFA+ study in Spain, with an average age of 60.5 years. Most participants (86.3%) had at least one parent with Alzheimer’s disease, putting them at increased risk. Participants completed the Minnesota Leisure Time Physical Activity Questionnaire at baseline (2013-2014) and again at follow-up (2016-2019), approximately 4 years apart. Researchers categorized participants based on their adherence to WHO physical activity recommendations (150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity activity weekly). During follow-up visits, participants underwent brain imaging, including structural MRI to measure cortical thickness in Alzheimer’s-vulnerable regions and PET scans to measure amyloid-beta burden. The researchers then performed multiple regression analyses to examine relationships between physical activity changes and brain outcomes, controlling for age, sex, education, genetic risk factors, and time between assessments.

Results

The study found that participants who remained sedentary showed lower cortical thickness in Alzheimer’s-vulnerable brain regions compared to those who maintained non-adherence, maintained adherence, or became adherent to WHO recommendations. Participants who became adherent to WHO recommendations showed lower amyloid-beta burden compared to those who became non-adherent. The research also revealed a dose-dependent relationship between increased physical activity amounts and lower amyloid-beta burden – the more participants increased their activity, the less amyloid they accumulated. These findings remained significant after controlling for cardiovascular and mental health factors, suggesting a potential direct link between physical activity and Alzheimer’s-related brain changes.

Limitations

The study has several limitations. Though physical activity was evaluated longitudinally, brain outcomes were measured at only one time point, making it difficult to establish causality. The researchers acknowledge the possibility of reverse causation, where early pathological changes might lead to increased sedentary behavior. Additionally, the study relied on self-reported physical activity questionnaires rather than objective measures. The subjective determination of activity intensities may have introduced bias in categorizing participants. The study’s focus on at-risk individuals also limits generalizability to the broader middle-aged population. Finally, the average 4-year interval between physical activity assessments means the study captured longer-term patterns rather than short-term habits.

Funding and Disclosures

The study was supported by multiple organizations including ‘la Caixa’ Foundation, the Alzheimer’s Association, an international anonymous charity, and various European and Spanish government agencies. Several authors disclosed potential conflicts of interest, including O.G-R who received lecture fees from Roche Diagnostics and research support from F-Hoffman La Roche, M.S-C who received lecture fees and served as a consultant for Roche Diagnostics and other pharmaceutical companies, and J.G-A who reported speaking fees from Chiesi España and AstraZeneca Pharmaceuticals unrelated to this study.

Publication Information

The paper “Physical activity changes during midlife link to brain integrity and amyloid burden” was published in Alzheimer’s & Dementia (2025, Volume 21, article number e70007) and was authored by Muge Akinci and colleagues from multiple Spanish institutions, primarily the Barcelona Institute for Global Health and the Barcelonaβeta Brain Research Center. The study is part of the larger ALFA (ALzheimer’s and FAmilies) project and was accepted on January 23, 2025, after revision of the original manuscript submitted in November 2024.

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