¹National Cheng Kung University, Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan, ²National Cheng Kung University, Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan, ³National Cheng Kung University, Institute of Clinical Medicine, Tainan, Taiwan, ⁴Taichung Veterans General Hospital, Department of Psychiatry, Chia-Yi Branch, Chia-Yi, Taiwan

Background: Physical exercise exerts robust neuroprotective and neuromodulatory effects in both healthy and clinical populations. Emerging human evidence using contrast-enhanced magnetic resonance imaging (MRI) indicates that long-term exercise enhances glymphatic influx and meningeal lymphatic flow. However, whether exercise modulates glymphatic-related microstructural perivascular diffusivity measurable using non-contrast diffusion MRI remains unclear.

Aims & Objectives: To investigate the effect of an 8-week structured physical exercise intervention on glymphatic function in previously sedentary healthy adults (engaging in <3 hours of moderate-intensity exercise per week) using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS).

Method: Nineteen right-handed, non-exercising healthy participants underwent MRI scanning before and after a structured exercise intervention. Imaging was performed on a 3-Tesla MRI scanner. Glymphatic function was assessed using the DTI-ALPS index, a diffusion-based surrogate marker of perivascular water diffusivity.

Results: Pairwise comparisons revealed a significant increase in right hemisphere DTI-ALPS following the exercise intervention (p = 0.048). A non-significant trend toward an increase was observed in the bilateral mean (right + left) ALPS index (p = 0.16), while no significant change was detected in the left hemisphere.

Discussion & Conclusions: These findings provide non-invasive evidence that regular physical exercise may enhance glymphatic-related perivascular diffusivity in healthy individuals. Our results extend previous contrast-based evidence by demonstrating that exercise-induced glymphatic modulation can be detected using a scalable, contrast-free MRI approach, supporting DTI-ALPS as a potential biomarker of brain waste clearance.