Atrophic brain signatures of mild forms of neurocognitive impairment in virally suppressed HIV infection

Madeleine J Nichols, Thomas M Gates, James R Soares, Kirsten J Moffat, Caroline D Rae, Bruce J Brew, Lucette A Cysique
2019 AIDS (London)  
There is a lack of evidence for the neurobiological underpinning of asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MNDs) in virally suppressed HIV-positive persons. We hypothesized that such mild impairment would be associated with focal brain atrophy. A cross-sectional observational study. Eighty-five virally suppressed HIV-positive and 44 geographically, demographically and lifestyle comparable HIV-negative men underwent anatomical MRI, neuropsychological
more » ... ation and HIV laboratory tests. Volumes of interest (VOI) from magnetic resonance (MR) images were extracted using FreeSurfer to yield grey and white matter volumes in regions associated with HIV-related brain injury. HIV-associated neurocognitive disorder (HAND) [ANI = 38%, MND = 13%, HIV-associated dementia (HAD) = 3% vs. neuropsychologically-normal] was classified using Global Deficit Score (GDS ≥0.5) and functional decline. Effects of HIV status on VOI were assessed with multivariate analyses controlling for family-wise error. HAND categories and HIV biomarker effects on VOI were assessed with multiple regression. Relative to the HIV-negative group, the HIV-positive group demonstrated subcortical grey (d = 0.50-0.60) and white matter (d = 0.43-0.69) atrophy, with relative cortical sparing (d = 0.23). ANI showed reduced medial-orbitofrontal white matter compared with NP-normal cases (P = 0.04). MND showed enlarged lateral ventricles (P = 0.02) and reduced caudal-middle-frontal white matter (P = 0.04), caudal-anterior-cingulate white matter (P = 0.006) and inferior-parietal white matter (P = 0.04) compared with neuropsychologically normal. Across the HIV-positive group, lower CD4/CD8 ratio was the strongest predictor of atrophy in subcortical regions. Across HAND categories, HIV disease duration uniquely predicted greater medial-orbitofrontal white matter atrophy only in ANI (P = 0.002). ANI shows specific frontal white matter atrophy to which HIV disease duration is a unique contributor. MND is characterized by more widespread subcortical atrophy.
doi:10.1097/qad.0000000000002042 pmid:30325766 fatcat:ylwmzhkx3fbrzllobj4liqow74