To validate a new automated method for calculation of analysis along the perivascular space (ALPS), a non-invasive measurement of glymphatic system, and examine the relationship between glymphatic system function and brain parenchymal destruction in a large community-based population.

In vivo evaluation of glymphatic system function in the brain using non-invasive methods has recently gained attention. Investigating how this measurement correlates with brain parenchymal disruptions within a large-scale population will enhance our understanding of the mechanisms underlying glymphatic system dysfunction.

In this cross-sectional investigation, we included a total of 1030 participants who underwent MRI scans from Shunyi study, a community-dwelling cohort. An automated method was built to calculate ALPS. Imaging markers of brain lesions were evaluated. Linear regression analysis and logistic regression were performed to investigate the relationship among variables.

Results: Among the 1030 non-demented participants included in the analysis, the average age was 57.14 ± 9.34 years, with 37.18% males. Automated ALPS showed high consistency with the manual calculation of this index (intraclass correlation coefficient=0.81, 95% CI: 0.662–0.898). Older age and male sex were associated with lower automated ALPS values (β=-0.051, SE=0.004, p<0.001, per 10 years, and β=-0.036, SE=0.008, p<0.001, respectively). The ALPS score was not associated with the traditional vascular risk factors after adjusting for age and sex. White matter hyperintensity (β=-2.458, SE=0.175, p<0.001), presence of lacunes (OR=0.004, 95% CI <0.002–0.016, p<0.001), and the number of cerebral microbleeds (β=-2.750, SE=0.662, p<0.001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (β=0.067, SE=0.007, p<0.001 and β=0.040, SE=0.014, p=0.006, respectively) independent of vascular brain damage.

Glymphatic system dysfunction may be implicated in both vascular and degenerative brain parenchymal lesions in non-demented general populations.