# Dose-response effects and mechanistic pathways linking physical exercise to brain volume and cognition: a systematic review and meta-analysis of randomized controlled trials

## TL;DR

This study shows that physical exercise increases brain volume, especially in older adults, and that these changes are linked to better cognitive function.

## Contribution

The study provides a systematic review and meta-analysis of how exercise affects brain volume and cognition, including dose-response effects and mediation pathways.

## Key findings

- Physical exercise significantly increases brain volume, with stronger effects in older individuals and with longer, more compliant exercise sessions.
- Exercise-induced brain volume changes are associated with improved cognitive function.
- Physical adaptations like muscle function and cardiorespiratory fitness mediate the relationship between exercise and cognitive outcomes through brain volume changes.

## Abstract

The dose-response effects of physical exercise on brain volume remain insufficiently understood, and it is yet to be established whether exercise-induced relative changes in brain volume translate into improvements in cognitive function. Furthermore, it remains unclear whether specific physical adaptations are associated with both exercise-related changes in brain volume and cognitive outcomes.

To address these gaps, we conducted a pre-registered systematic review and multilevel meta-analysis of 59 randomized controlled trials comprising a total of 5,099 participants. Comprehensive literature searches were carried out in PubMed, PsycINFO, Embase, and Web of Science up to August 2024. The meta-analysis examined overall effects of physical exercise on brain volume, investigated dose-response effects across relevant moderators, and explored potential mediation pathways linking exercise-induced relative changes in brain volume to cognitive outcomes.

This study found that physical exercise had a significant effect on brain volume. Dose-response analyses further revealed that this effect was more pronounced among individuals of older age, with longer intervention durations and higher compliance. Exercise sessions lasting 40–60 min were associated with the most robust effects on brain volume. Post-hoc analyses suggest that these effects are more likely attributable to the preservation of brain volume rather than substantial volumetric increases. In addition, regression analysis demonstrated a significant positive association between exercise-induced relative changes in brain volume and cognitive function. Moreover, mediation analyses indicated that exercise-induced physical adaptations in muscle function, motor performance, and cardiorespiratory fitness were indirectly associated with cognitive performance through their effects on relative brain volume change.

These findings indicate that physical exercise exerts beneficial effects on brain volume, particularly under conditions such as older age, sufficient exercise duration, and high compliance. Exercise-induced relative changes in brain volume were significantly associated with cognitive function and served as a mediator between physical adaptations and cognitive outcomes. Together, these results provide a mechanistic foundation and practical insights for designing targeted exercise interventions to promote brain health in aging populations.

PROSPERO CRD42024525635.

The online version contains supplementary material available at 10.1186/s11556-025-00398-3.