Exploring cerebral small vessel disease, choroid plexus, demographics and vascular risk factors that affect glymphatic function.

Background: Cerebral small vessel disease (CSVD) is a major contributor to cognitive decline and dementia. The glymphatic system, a recently discovered brain waste clearance system, plays a critical role in maintaining brain health. This study investigates glymphatic dysfunction in CSVD using diffusion tensor imaging along perivascular spaces (DTI-ALPS) and enlarged perivascular spaces (EPVS), to identify key risk factors and modifiable influences.

Methods: 373 participants were recruited and underwent magnetic resonance imaging. Multivariable regression and restricted cubic splines (RCS) were performed to investigate the associations between demographics, vascular risk factors, choroid plexus volume (CPV), imaging markers of CSVD, and time of day (TOD) with the glymphatic system estimated by DTI-ALPS and PVS.

Results: L-ALPS correlated with age (β = - 0.233, p < 0.001), CPV (β = - 0.100, p = 0.047), and sex (β = 0.103, p = 0.027). R-ALPS correlated with age (β = - 0.108, p = 0.040), Fazekas score (β = - 0.151, p = 0.006), male sex (β = 0.209, p < 0.001), and cerebral microbleeds (β = - 0.146, p = 0.004). The risk factors for severe BG-PVS were age (OR: 1.090, P < 0.001) and Fazekas score (OR: 2.243, P < 0.001). L-ALPS correlated with TOD (β = - 0.091, p = 0.039), particularly in females (β = - 0.147, p = 0.016).

Conclusion: Age, sex (male), white matter hyperintensity, CPV enlargement, and cerebral microbleeds are risk factors for glymphatic dysfunction. Circadian rhythms may modulate glymphatic activity.