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.

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.

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