Glymphatic system dysfunction mediates the relationship between deep medullary vein alterations and cognitive impairment in cerebral small vessel disease

BACKGROUND: This study investigates how structural changes in deep medullary vein (DMV), glymphatic system dysfunction, and cognitive decline are interconnected in cerebral small vessel disease (CSVD), with a focus on whether impaired glymphatic function acts as a mediator in this relationship. METHODS: Clinical and MRI data from 93 CSVD patients were retrospectively analyzed. DMV burden was assessed using a semiquantitative scoring system (0-3 points per region), based on the visibility of DMVs in six anatomical regions on susceptibility-weighted imaging, yielding a total score ranging from 0 to 18. Glymphatic system function was evaluated using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Global cognitive function was assessed with the Montreal Cognitive Assessment (MoCA). Spearman correlation analysis, general linear modeling, and mediation analysis were conducted to examine the relationships among the variables. RESULTS: DMV scores(which higher scores indicate poorer venous visibility)were significantly negatively correlated with MoCA scores (r = -0.48, p< 0.001) and with the DTI-ALPS index (r = -0.28, p < 0.001), while the DTI-ALPS index was positively correlated with MoCA scores (r= 0.35, p < 0.05). Mediation analysis indicated that the DTI-ALPS index partially mediated the effect of DMV burden on cognitive performance, accounting for 14.08% of the total effect. CONCLUSIONS: This study suggests that DMV structural abnormalities may exacerbate CSVD-related cognitive impairment by disrupting glymphatic function. DMV scoring may serve as a potential imaging biomarker, providing a foundation for early identification and intervention.