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

Yilin Wang^1,2, Wei He², Yongbo Li³

¹Department of Radiology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

Frontiers in Neurology

|June 22, 2026

Abstract

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.

Insights

The diffusion tensor imaging along the perivascular spaces (DTI-ALPS) index shows promise for predicting cognitive impairment in tuberculous meningitis (TBM) patients, correlating with cognitive function and prognosis.

Area of Science:

Neuroimaging
Neurology
Infectious Diseases

Background:

Tuberculous meningitis (TBM) often leads to mild cognitive impairment (MCI).
Glymphatic system dysfunction, assessed via imaging, is linked to cognitive decline but its role in TBM is unclear.
Cerebrospinal fluid (CSF) protein changes in TBM patients are not fully understood in relation to cognitive function.

Purpose of the Study:

To investigate the relationship between glymphatic function markers, cognitive performance, and CSF proteins in TBM patients using fMRI.
To evaluate the diagnostic and prognostic potential of glymphatic imaging markers in TBM-associated cognitive impairment.

Main Methods:

123 participants (61 healthy controls, 30 TBM-nonMCI, 32 TBM-MCI) underwent MRI and cognitive tests.
Evaluated perivascular space (PVS) load, diffusion-tensor imaging along the perivascular spaces (DTI-ALPS) index, and choroid plexus volume (CPV).
Analyzed CSF proteomics and used correlation and mediation analyses to link glymphatic metrics, CSF proteins, and cognition.

Main Results:

TBM patients had altered hippocampal PVS and choroid plexus volume (CPV) compared to controls; TBM-MCI patients showed lower ALPS and higher basal ganglia PVS.
ALPS indices and hippocampal PVS correlated positively with cognitive measures, while CPV showed inverse correlations.
The ALPS index predicted cognitive prognosis (AUC=0.857) and distinguished TBM-MCI from controls (AUC=0.719), with CSF proteins not mediating these relationships.

Conclusions:

Altered perivascular clearance markers (ALPS, CPV) are associated with cognitive decline in TBM.
The ALPS index is a potential biomarker for predicting cognitive dysfunction and prognosis in TBM.
Further research into glymphatic system mechanisms in TBM is warranted.

Read full analysis

Keywords:

choroid plexus cognitive function diffusion tensor imaging along the perivascular space glymphatic system tuberculous meningitis

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