Altered Diffusion Tensor Image Analysis Along the Perivascular Space in People With Human Immunodeficiency Virus: Association With Cognition and Diagnostic Utility for Asymptomatic Neurocognitive Impairment.

Abstract

This aim of this work was to investigate glymphatic function in people with human immunodeficiency virus type 1 (HIV-1) using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its associations with cognition and clinical status, as well as its diagnostic utility in identifying asymptomatic neurocognitive impairment (ANI). Forty people with HIV (PWH) with ANI (PWH-ANI), 44 PWH with normal cognition (PWH-NC), and 29 age-, sex-, and education-matched persons without HIV underwent MRI and neuropsychological assessments. DTI-ALPS indices were calculated and their group differences were evaluated using general linear models. Partial correlation and multivariate regression analyses were conducted to assess associations between DTI-ALPS indices and cognitive or clinical variables. Mediation analyses were used to examine whether DTI-ALPS mediated the effect of HIV on cognition. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance. DTI-ALPS indices were significantly lower in PWH-ANI than persons without HIV and PWH-NC (all P < .01), with no differences between persons without HIV and PWH-NC. Among PWH, lower DTI-ALPS was associated with higher cognitive T scores (ie, poorer performance) in attention/working memory, speed of information processing, and abstract/executive function (all false discovery rate-adjusted P < .05). DTI-ALPS for the bilateral hemisphere (DTI-ALPS_B) emerged as the only independent predictor and partially mediated the relationship between HIV status and these cognitive domains. ROC analysis showed that the combined model of DTI-ALPS_B and Montreal Cognitive Assessment (MoCA) outperformed MoCA alone (AUC, 0.782 and 0.619, respectively; P = .001). Reduced DTI-ALPS is evident in PWH-ANI and was associated with and mediated cognitive impairment. DTI-ALPS may serve as a noninvasive biomarker facilitating early detection of PWH-ANI.