MRI markers of glymphatic dysfunction in tuberculous meningitis: associations with CSF proteins and cognitive impairment.

OBJECTIVES

Tuberculous meningitis (TBM), a central nervous system infection, is frequently complicated by mild cognitive impairment (MCI). Although imaging markers of glymphatic function have been shown to correlate with cognitive decline, its role in TBM remains unrevealed. This study aims to examine the associations among glymphatic function, cognitive performance, and cerebrospinal fluid proteins in patients with TBM using functional magnetic resonance imaging (fMRI).

METHODS

This study enrolled 123 participants (61 healthy controls (HCs), 30 TBM-nonMCI, 32 TBM-MCI) who underwent MRI scanning and cognitive assessments. The perivascular space (PVS) load, diffusion-tensor imaging along the perivascular spaces (DTI-ALPS) index and choroid plexus volume (CPV) were calculated to evaluate lymphatic function. CSF proteomics were analyzed in TBM patients. Then, partial correlation and mediation analyses examined the associations among CSF proteins, lymphatic metrics, and cognition. Receiver operating characteristic curves were used to evaluated the predictive capacity for TBM-MCI diagnosis and 6-to 12-month treatment outcomes.

RESULTS

Compared with HCs, all patients showed smaller hippocampal PVS volume fraction and larger CPV, and the TBM-MCI group exhibited lower ALPS and higher basal ganglia PVS. ALPS indices positively correlated with cognitive measures (SDMT, MMSE), while hippocampal PVS positively correlated with multiple cognitive domains; CPV exhibited opposite correlations. The right CPV fully mediated the relationship between the right ALPS-MMSE and the right ALPS index, distinguishing TBM-MCI from HCs (AUC = 0.719). The left ALPS index predicted a 6- to 12-month cognitive prognosis (AUC = 0.857), with CSF proteins not mediating glymphatic-cognitive relationships.

CONCLUSION

The association between imaging markers suggestive of altered perivascular clearance and cognitive decline in tuberculous meningitis underscores the potential mechanistic roles of the ALPS and CPV, positioning the ALPS index as a promising biomarker candidate for prognosis and cognitive dysfunction.