Altered Diffusion Tensor Image Analysis Along the Perivascular Space in People Living with HIV: Association with Cognition and Diagnostic Utility for Asymptomatic Neurocognitive Impairment

BACKGROUND: To investigate glymphatic function in people living with HIV (PLWH) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS), and explore its associations with cognition and clinical status, as well as its diagnostic utility in identifying asymptomatic neurocognitive impairment (ANI). MATERIALS AND METHODS: Forty PLWH with ANI (PLWH-ANI), 44 PLWH with normal cognition (PLWH-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. RESULTS: DTI-ALPS indices were significantly lower in PLWH-ANI than persons without HIV and PLWH-NC (all p<0.01), with no differences between persons without HIV and PLWH-NC. Among PLWH, lower DTI-ALPS were associated with higher cognitive T scores (i.e., poorer performance) in attention/working memory, speed of information processing, and abstract/executive function (all FDR-p<0.05). 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 MoCA outperformed MoCA alone (AUC = 0.782, 0.619; p = 0.001). CONCLUSIONS: Reduced DTI-ALPS is evident in PLWH-ANI, and was associated with and mediated cognitive impairment. DTI-ALPS may serve as a non-invasive biomarker facilitating early detection of PLWH-ANI.