# Glymphatic dysfunction and cognitive impairment in tuberculous meningitis: insights from diffusion tensor imaging along the perivascular space (DTI-ALPS)

## TL;DR

This study explores how glymphatic system dysfunction in tuberculous meningitis is linked to cognitive impairment using a new imaging method.

## Contribution

The study introduces the DTI-ALPS index as a novel non-invasive biomarker for detecting cognitive impairment in TBM.

## Key findings

- TBM patients showed reduced ALPS indices and increased diffusivity in specific brain regions compared to healthy controls.
- Lower ALPS indices in TBM patients with MCI correlated with worse performance on specific cognitive tests.
- The ALPS index demonstrated moderate predictive value for identifying TBM patients at risk of MCI.

## Abstract

Tuberculous meningitis (TBM), a severe central nervous system infection, carries significant mortality and long-term neurological morbidity. While cognitive impairment is a common consequences of TBM, the contribution of glymphatic system dysfunction to this process remains poorly characterized.

To investigate glymphatic function in TBM patients using the diffusion tensor imaging (DTI)-derived along the perivascular space (ALPS) index and evaluate its utility in detecting and predicting mild cognitive impairment (MCI).

This cross-sectional study enrolled 62 TBM patients and 61 matched healthy controls (HCs). ALPS indices (left/right/whole-brain) were computed from DTI data. Cognitive function was assessed using MMSE, MoCA, TMT-A/B, CDT, VFT, DST, and SDMT. Group comparisons, partial correlation analyses, and ROC curve assessments were performed to examine relationships between glymphatic function and cognitive performance.

TBM patients demonstrated significantly reduced ALPS indices (all p < 0.05) and elevated diffusivity in projection (Dyproj) and association (Dzassoc) fiber regions compared to HCs. Within the TBM-MCI subgroup, left Dyproj/Dzassoc correlated negatively with CDT scores (p < 0.05), while ALPS indices showed: (1) negative correlations with TMT-A/B (left/whole-brain), (2) positive correlations with SDMT (right/whole-brain). MCI patients exhibited significantly lower right/whole-brain ALPS indices than non-MCI counterparts (p < 0.05), with ROC analysis demonstrating moderate predictive value (AUC = 0.70).

The DTI-ALPS index effectively captures glymphatic dysfunction in TBM and correlates with domain-specific cognitive deficits. As a non-invasive biomarker, it shows promise for early identification of TBM patients at risk for MCI, potentially facilitating timely intervention to mitigate cognitive decline.