A groundbreaking study published in the prestigious journal Alzheimer’s & Dementia has unveiled compelling evidence that increasing physical activity during midlife—specifically between the ages of 45 and 65—may play a crucial role in preventing or delaying the onset of Alzheimer’s disease. This revelation comes from a collaborative effort between the Barcelona Institute for Global Health (ISGlobal) and the Barcelonaβeta Brain Research Center (BBRC), highlighting the urgent need to promote physical exercise among middle-aged adults as a strategic measure against neurodegeneration.
Alzheimer’s disease, a debilitating neurodegenerative condition marked by progressive memory loss and cognitive decline, affects millions worldwide with vast social and economic consequences. While previous research has firmly established the benefits of exercise in reducing cardiovascular and mental health risks, this new study delves deeper into the neuropathological underpinnings connecting physical activity directly to Alzheimer’s disease progression. An estimated 13% of Alzheimer’s cases globally are attributed to insufficient physical exercise, underscoring inactivity as a significant modifiable risk factor.
Led by ISGlobal researcher Eider Arenaza-Urquijo, the study meticulously followed 337 middle-aged adults from Catalonia with a genetic predisposition to Alzheimer’s, all participants of the ALFA+ longitudinal cohort. Over a four-year monitoring period, the researchers tracked changes in participants’ physical activity levels through detailed questionnaires while simultaneously employing advanced neuroimaging technologies to assess alterations in brain structure and function. This dual approach allowed a comprehensive evaluation of the interaction between lifestyle modification and brain health biomarkers.
Participants were stratified into three categories based on adherence to World Health Organization (WHO) guidelines: adherent individuals meeting the recommended 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week; non-adherent individuals engaging in some but insufficient exercise; and sedentary individuals reporting no physical activity. The study’s longitudinal design and the use of neuroimaging biomarkers provided unprecedented insight into how lifestyle changes in midlife influence Alzheimer’s pathology.
One of the most striking findings of the research was the observation that individuals increasing their physical activity to meet WHO standards exhibited significantly less accumulation of beta-amyloid (Aβ) in the brain. Beta-amyloid proteins are known to disrupt neuronal communication and initiate the earliest pathological changes in Alzheimer’s disease, making their reduction a targeted avenue for prevention. The effect observed was dose-dependent, indicating that greater increments in exercise correlated with more substantial reductions in amyloid burden.
In addition to amyloid reduction, the study identified a notable preservation of cortical thickness in brain regions vulnerable to Alzheimer’s pathology, particularly within the medial temporal lobe—a brain area instrumental in memory formation. Cortical thinning in this region is a hallmark of early neurodegenerative processes, thus implying that physical activity confers neuroprotective benefits by maintaining structural brain integrity. Importantly, even participants who performed less than the recommended activity showed greater cortical thickness than completely sedentary individuals, underscoring that any amount of exercise may impart cognitive health advantages.
These results illuminate a critical paradigm shift: the protective effects of physical activity are not solely about reaching strict exercise quotas but are strongly linked to upward trajectories in activity levels over time. Incremental increases in physical effort, even if modest, appear capable of modulating disease biomarkers and bolstering brain resilience. This finding stresses that public health strategies should encourage progressive enhancement of physical activity, making prevention more attainable and individualized.
The research also adds nuance to our understanding of Alzheimer’s disease pathophysiology by bridging lifestyle factors with quantifiable neurobiological changes. It suggests that exercise may exert direct effects on amyloid metabolism and neuroanatomical preservation, challenging the traditional view that benefits are mediated only through cardiovascular or mood improvements. Though the exact molecular mechanisms remain under investigation, hypotheses include exercise-induced enhancement of cerebral blood flow, neurotrophic factor release, and modulation of inflammatory pathways—each contributing to a brain environment hostile to amyloid accumulation.
Given the study’s robust observational design and longitudinal follow-up, these findings carry significant weight for clinical and public health initiatives. Targeting midlife adults—particularly those with a family history of Alzheimer’s—offers a strategic window for intervention before irreversible pathology or cognitive impairment ensues. Health agencies worldwide may consider revising guidelines to emphasize not just recommended exercise thresholds but also the importance of increasing activity relative to baseline habits.
Dr. Müge Akıncı, the doctoral researcher and lead author, highlights the importance of sustained behavioral change. “Our data indicate that promoting even small increases in physical activity yields measurable benefits to brain structure and amyloid load. This opens promising avenues for tailored interventions that can be realistically adopted by at-risk populations,” she explains.
Furthermore, the collaboration between ISGlobal and BBRC exemplifies how multidisciplinary research—integrating epidemiology, neuroimaging, and behavioral sciences—can unravel complex interactions between lifestyle and neurodegeneration. The study serves as a catalyst for future investigations aimed at identifying optimal exercise modalities, intensities, and durations to maximize neuroprotective effects.
As Alzheimer’s disease continues to impose an escalating global burden, these insights are a pivotal step toward non-pharmacological prevention strategies that empower individuals to take active roles in safeguarding brain health. Encouragingly, the research reinforces that physical activity during midlife is not merely beneficial for general health but may be one of the most potent tools against this devastating disease.
In light of these compelling findings, the researchers advocate for integrating physical activity promotion into public health policies, workplace wellness programs, and community-level initiatives. Such comprehensive efforts could translate into meaningful reductions in Alzheimer’s incidence over the coming decades, alleviating personal and societal hardship.
Ultimately, this landmark study charts a hopeful course, affirming that lifestyle modifications—namely increased and sustained physical exercise during middle age—can directly influence the biological processes at the core of Alzheimer’s disease. These discoveries invigorate the quest for accessible, effective prevention, underscoring exercise not only as medicine for the body but also as a cornerstone of brain health preservation.
Subject of Research: People
References:
Akinci, 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.
Keywords: Alzheimer disease, Public health, Disease prevention, Physical exercise, Cohort studies, Risk factors
