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

Abstract 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.