MRI Evaluation of Glymphatic Dysfunction in Cerebral Small Vessel Disease: Hypertensive vs. Normotensive Patients

ABSTRACT The glymphatic system (GS) serves as the brain's waste clearance pathway, with dysfunction implicated in neurodegenerative disorders—particularly cerebral small vessel disease (CSVD). As hypertension is a modifiable risk factor strongly linked to CSVD progression, we compared magnetic resonance imaging‐derived (MRI‐derived) GS metrics between hypertensive and normotensive CSVD patients. So, in this study, we retrospectively analyzed 72 clinically diagnosed CSVD patients (37 hypertensive [CSVD_HT + ], 35 normotensive [CSVD_HT − ]), and 40 age‐matched healthy controls (HCs). Key MRI‐derived GS indices included: perivascular space volume fraction (PVS‐VF), diffusivity along perivascular spaces (ALPS index), free water in white matter (FW‐WM), and choroid plexus volume (Chp). CSVD patients exhibited abnormal MRI‐derived indices, Compared to CSVD_HT − individuals, CSVD_HT + were characterized by lower ALPS index, higher FW‐WM and hypertrophy of Chp. Random systolic blood pressure (SBP) negatively correlated with ALPS index ( r = −0.220, p = 0.055), while positively correlating with FW‐WM ( r = 0.460, p < 0.001), and Chp volume ( r = 0.310, p = 0.006). Cognitive assessments revealed associations between ALPS index and memory scores ( r = 0.280, p = 0.020). These findings suggest that elevated SBP exacerbates GS impairment in CSVD, underscoring the critical role of blood pressure management. Longitudinal studies are needed to confirm these observations.