A new study reveals that physical activity during midlife may protect the brain from early signs of Alzheimer’s disease (AD), even in individuals at higher risk.
A recent article published in the journal Alzheimer’s & Dementia sheds light on how becoming or staying physically active in midlife may lower brain changes linked to AD. Specifically, engaging in exercise—even below recommended levels—was associated with improved brain structure and reduced amyloid-β (Aβ) buildup.
Understanding the Early Phase of Alzheimer’s
Alzheimer’s disease often begins long before symptoms appear, with early brain changes such as:
- Amyloid-β (Aβ) buildup
- Neurodegeneration
- Cortical thinning in vulnerable brain areas
These changes can be detected years before memory loss and cognitive decline set in. With up to one-third of Alzheimer’s cases linked to modifiable lifestyle factors, researchers are increasingly focused on prevention strategies—especially those involving physical activity.
Why Midlife Activity Matters
Midlife, typically defined as the ages of 40 to 65, is considered a crucial period for brain health. This is when age-related brain changes begin, particularly in individuals with a family history or genetic predisposition to Alzheimer’s.
While past studies have suggested that physical activity reduces AD biomarkers, few have analyzed how changes in physical activity over time affect the progression of these brain changes.
The Study at a Glance
Researchers analyzed data from 337 middle-aged adults (ages 45–65) who were cognitively healthy but at risk for Alzheimer’s. Most participants had a family history of AD.
Participants were tracked over a 4-year period as part of a larger study in Catalonia, Spain. Key methods included:
- Self-reported physical activity: Measured in weekly minutes of moderate to vigorous exercise.
- Brain imaging: PET scans for Aβ burden and MRI for cortical thickness.
- WHO guidelines: Participants were grouped by their adherence to the World Health Organization’s physical activity recommendations.
WHO Guidelines for Physical Activity
The World Health Organization recommends:
- At least 150 minutes of moderate-intensity physical activity per week, or
- 75 minutes of vigorous-intensity physical activity per week.
Key Findings
1. Becoming Active Reduces Alzheimer’s Markers
Participants who became adherent to WHO guidelines during the study had:
- Lower amyloid-β burden compared to those who became non-adherent.
- Greater cortical thickness in AD-sensitive regions compared to those who remained sedentary.
Even those who didn’t meet full guidelines but increased activity still showed better brain structure than those who stayed inactive.
2. Staying Active Preserves Brain Structure
Participants who maintained an active lifestyle had:
- Significantly thicker cortex in brain regions vulnerable to Alzheimer’s.
- Healthier brain aging profiles than sedentary individuals.
3. Sedentary Behavior Was Harmful
Those who remained sedentary experienced:
- Reduced cortical thickness in AD-sensitive brain regions.
- No reduction in Aβ burden, indicating ongoing Alzheimer’s-related changes.
4. A Dose-Response Relationship
Researchers found a dose-response effect: more activity correlated with a lower Aβ burden. However, this effect was not observed for cortical thickness, which suggests that structural brain changes may respond differently to exercise than amyloid accumulation.
How Did the Study Control for Other Factors?
To ensure the results were not due to other influences, the study accounted for:
- Age
- Sex
- Education
- APOE-ε4 gene status (a genetic risk factor for AD)
- Cardiovascular health
- Mental health symptoms, such as depression and anxiety
Even after adjusting for these variables, the association between physical activity and brain health remained strong.
Study Strengths and Limitations
Strengths
- Longitudinal design (tracked over 4 years)
- Objective brain imaging (PET and MRI)
- Focus on high-risk individuals
Limitations
- Observational design (cannot prove causality)
- Self-reported activity levels
- Lack of ethnic diversity (99.4% of participants were Caucasian)
- Brain outcomes only measured at follow-up, limiting insights into timing and causality
- Other factors like sleep and neurogenesis were not assessed
Why This Matters
This study is one of the first to show that becoming active in midlife—not just being active from the start—can make a measurable difference in brain health for those at risk of Alzheimer’s. Importantly, even partial adherence to WHO physical activity guidelines provided neuroprotective benefits.
Bottom Line
Adopting a more active lifestyle—even if it’s below official guidelines—could offer meaningful protection against Alzheimer’s disease. The earlier in midlife these habits are formed, the better the potential outcomes for brain resilience.
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