Age- and sex-related glymphatic differences and hemispheric asymmetry in healthy adults at 7.0T magnetic resonance imaging.

Abstract

Background: The glymphatic system plays a critical role in cerebral waste clearance and has been implicated in neurodegenerative and cerebrovascular disorders. However, normative variations in glymphatic structure and function across age, sex, and hemispheric organization in healthy adults remain incompletely characterized.

Methods: Using ultra-high-field 7.0T MRI, we quantitatively assessed structural and functional glymphatic markers in 80 healthy adults. Perivascular space (PVS) number and volume were measured in the basal ganglia (BG) and midbrain (Mid), and glymphactic function was evaluated using the diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index. Participants were stratified by age and sex. False discovery rate (FDR) correction was applied to control for multiple comparisons.

Results: Robust age-related effects were observed. Older participants exhibited significantly greater PVS burden in the BG and Mid and lower right-hemispheric DTI-ALPS indices compared with younger adults. Age correlated positively with PVS number and left BG PVS volume, and negatively with the right DTI-ALPS index. Several sex effects did not survive FDR correction but showed moderate-to-large effect sizes in age-stratified analyses, suggesting potential sex-by-age interactions. Hemispheric analyses revealed a consistent right-dominant PVS burden in the midbrain, evident across age groups, whereas BG PVS burden and DTI-ALPS indices were largely symmetric.

Conclusion: These findings demonstrate that glymphatic structure and function in healthy adults are strongly influenced by aging, exhibit age-dependent sex-related trends, and show region-specific hemispheric asymmetry. This study provides high-resolution normative reference data for glymphatic imaging and informs future investigations of early or subclinical glymphatic dysfunction.