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

OBJECTIVE: There is a lack of evidence for the neurobiological underpinning of Asymptomatic Neurocognitive Impairment (ANI) and Mild Neurocognitive disorders (MND) in virally-suppressed HIV + persons. We hypothesized that such mild impairment would be associated with focal brain atrophy.

DESIGN: Cross-sectional observational study.

METHODS: 85 virally-suppressed HIV + and 44 geographically, demographically, and lifestyle comparable HIV- men underwent anatomical MRI, neuropsychological evaluation, and HIV laboratory tests. Volumes of interest (VOI) from MR images were extracted using FreeSurfer to yield grey (GM) and white matter (WM) volumes in regions associated with HIV-related brain injury. HAND (ANI = 38%, MND = 13%, HIV-associated dementia (HAD) = 3% vs. neuropsychologically (NP)-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.

RESULTS: Relative to the HIV- group, the HIV + group demonstrated subcortical grey (d = 0.50-0.60) and WM (d = 0.43-0.69) atrophy, with relative cortical sparing (d = 0.23). ANI showed reduced medial-orbitofrontal WM compared to NP-normal cases (p = .04). MND showed enlarged lateral ventricles (p = .02) and reduced caudal-middle-frontal WM (p = .04), caudal-anterior-cingulate WM (p = .006), and inferior-parietal WM (p = .04) compared to NP-normal. Across the HIV + 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 WM atrophy only in ANI (p = .002).

CONCLUSIONS: ANI shows specific frontal WM atrophy to which HIV disease duration is a unique contributor. MND is characterised by more widespread subcortical atrophy.