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

## TL;DR

This study finds that poor visibility of deep medullary veins in brain imaging is linked to worse cognitive function in patients with cerebral small vessel disease, partly due to disrupted glymphatic system function.

## Contribution

The study identifies glymphatic system dysfunction as a mediator between deep medullary vein alterations and cognitive decline in cerebral small vessel disease.

## Key findings

- Higher deep medullary vein scores correlate with lower cognitive scores and worse glymphatic system function.
- Glymphatic system dysfunction partially mediates the effect of deep medullary vein burden on cognitive performance.
- Deep medullary vein scoring may serve as an imaging biomarker for cognitive impairment in cerebral small vessel disease.

## Abstract

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.

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.

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.

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.