Individuals who meet or exceed physical activity recommendations exhibit distinct age-related differences in hippocampal macrostructure and microstructure compared with those who do not, with MVPA moderating age-related changes particularly in the left hippocampus.
Key Findings
Results
Among low-active individuals, age was associated with widespread multivariate differences in hippocampal macrostructure and microstructure, characterized by lower regionally specific thickness and surface area and a higher T1w/T2w ratio.
Low-active group was defined as engaging in ≥0 to <150 min/week of moderate-to-vigorous physical activity (MVPA)
Hippocampal thickness, surface area, and T1w/T2w ratio were derived from unfolded hippocampal surfaces using HippUnfold
Age effects included both linear and quadratic components tested via multivariate general linear models
Sample consisted of 555 cognitively healthy adults ages 36–90 years from the Human Connectome Project-Aging cohort
Results
MVPA moderated age-related changes in the left hippocampus, with significant effects observed in both the moderate- and high-MVPA groups.
Moderately active group was defined as ≥150 to <300 min/week of MVPA; highly active group as ≥300 min/week
MVPA × age interactions were tested separately for each hemisphere
Effects in moderate- and high-MVPA groups were characterized by greater surface area and T1w/T2w ratio compared to low-active group
These activity-associated effects were also associated with lower thickness values in the left hippocampus
No equivalent moderation effect was reported for the right hippocampus
Methods
Physical activity categories were defined according to World Health Organization 2020 guidelines, and weekly MVPA was measured using the International Physical Activity Questionnaire.
Three activity categories used: low-active (≥0–<150 min/week), moderately active (≥150–<300 min/week), and highly active (≥300 min/week)
The International Physical Activity Questionnaire was the self-report instrument used to quantify weekly MVPA
Participants were drawn from the Human Connectome Project-Aging cohort (n=555)
Models controlled for demographic and health covariates
Methods
The study used unfolded hippocampal surface mapping (HippUnfold) to capture hippocampal morphology beyond volumetric analyses, including thickness, surface area, and microstructural T1w/T2w ratio.
Volumetric analyses were identified as potentially obscuring nuanced changes in cortical geometry, particularly in heavily folded hippocampal regions
HippUnfold was used to derive hippocampal thickness, surface area, and T1w/T2w ratio from unfolded hippocampal surfaces
The T1w/T2w ratio served as a proxy for hippocampal microstructure
The study is cross-sectional in design, limiting causal inference
Background
The study identified discrepancies in the existing literature on physical activity and hippocampal structure as potentially attributable to a historical focus on volumetric analyses that obscure nuanced morphological changes.
The authors note that prior cross-sectional evidence on physical activity and hippocampal morphology remains 'limited and inconsistent'
Hippocampal folding was specifically cited as a region where volumetric methods may fail to capture relevant geometric changes
The use of hippocampal macrostructure (thickness and surface area) alongside microstructure (T1w/T2w ratio) was presented as a methodological advancement over prior work
What This Means
This research suggests that how physically active a person is may influence how their hippocampus — a brain region important for memory and learning — changes as they age. Using brain imaging data from 555 adults between the ages of 36 and 90, the researchers found that people who did little to no moderate-to-vigorous physical activity showed widespread age-related differences in the hippocampus, including thinner tissue, smaller surface area, and changes in tissue composition. In contrast, people who met or exceeded the WHO's recommended 150 minutes per week of moderate-to-vigorous activity showed a different pattern of age-related differences, particularly in the left hippocampus, including greater surface area and different tissue properties.
One notable aspect of this study is its use of a more detailed method of analyzing the hippocampus than most prior research. Rather than simply measuring overall hippocampal volume, the researchers used a technique called HippUnfold to map the surface of the hippocampus in detail, capturing information about thickness, surface area, and tissue microstructure. This approach revealed patterns that a simple volume measurement would likely miss, which may help explain why earlier studies on this topic have produced mixed results.
This research suggests that staying physically active — even at moderate levels — may be associated with a healthier pattern of brain aging in the hippocampus. Because the study is cross-sectional (meaning it looked at people at one point in time rather than following them over years), it cannot prove that physical activity directly causes these brain differences. Nonetheless, the findings add to a growing body of evidence linking regular physical activity to better brain health in middle-aged and older adults.
Montero-Herrera B, Wessinger C, Etnier J, Drollette E, Park K, Herring M, et al.. (2026). Physical Activity Is Associated With Age-Related Differences in Hippocampal Macrostructure and Microstructure in Middle-Aged and Older Adults.. Hippocampus. https://doi.org/10.1002/hipo.70130