Glymphatic dysfunction in HIV: a resting-state functional magnetic resonance imaging biomarker linking cognitive impairment and immune suppression.

OBJECTIVE

To investigate glymphatic dysfunction in people with HIV (PWH) and its associations with immunological status and cognitive function, utilizing the coupling strength of global blood-oxygen-level-dependent and cerebrospinal fluid (gBOLD-CSF).

DESIGN

Retrospective study of 75 PWH and 52 non-HIV controls undergoing neuropsychological tests and resting-state functional magnetic resonance imaging (rs-fMRI).

METHODS

GBOLD-CSF coupling, Montreal Cognitive Assessment (MoCA) and seven cognitive domain scores were calculated. Group difference in gBOLD-CSF coupling strength was analyzed using a general linear model, adjusting for age, sex, and education. Partial correlation analyses were performed to examine the correlations of cognitive performance and immunological status with gBOLD-CSF coupling. Multivariate regression analysis was utilized to further evaluate the associations of gBOLD-CSF coupling with cognition.

RESULTS

PWH exhibited significantly weaker gBOLD-CSF coupling than non-HIV controls ( P  = 0.018) and revealed impairments in attention/working memory, speed of information processing, and abstract/executive function (all P  < 0.05). Reduced gBOLD-CSF coupling was associated with deficits in MoCA scores ( r  = -0.332, P  = 0.004), verbal fluency ( r  = 0.245, P  = 0.038), attention/working memory ( r  = 0.240, P  = 0.042), speed of information processing ( r  = 0.245, P  = 0.038), and abstract/executive function ( r  = 0.241, P  = 0.042) in PWH. Multivariate regression analysis showed gBOLD-CSF coupling was the only independent predictor for speed of information processing ( β = 0.410, P  = 0.031) and MoCA scores ( β = -0.399, P  = 0.037). Weaker gBOLD-CSF coupling was correlated with lower nadir and current CD4 + cell count ( r  = -0.379, P  = 0.019; r  = -0.321, P  = 0.049, respectively).

CONCLUSION

Reduced gBOLD-CSF coupling in PWH suggests glymphatic dysfunction and was associated with cognitive impairment and HIV-related immune suppression. It may serve as a noninvasive biomarker for monitoring cognitive disturbances and disease progression in HIV.