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

BACKGROUND

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.

OBJECTIVE

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).

METHODS

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.

RESULTS

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).

CONCLUSION

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.