Multi-label, multi-domain learning identifies compounding effects of HIV and cognitive impairment

Older individuals infected by Human Immunodeficiency Virus (HIV) are at risk for developing HIV-Associated Neurocognitive Disorder (HAND), i.e., from reduced cognitive functioning similar to HIV -negative individuals with Mild Cognitive Impairment (MCI) or to Alzheimer's Disease (AD) if more severely affected. Incompletely understood is how brain structure can serve to differentiate cognitive im-pairment (CI) in the HIV-positive (i.e., HAND) from the HIV-negative cohort (i.e., MCI and AD). To that end, we designed a multi-label classifier that labels the structural magnetic resonance images (MRI) of individuals by their HIV and CI status via two binary variables. Proper training of such an approach tradi-tionally requires well-curated datasets containing large number of samples for each of the corresponding four cohorts (healthy controls, CI HIV-negative adults a.k.a. CI-only, HIV-positive patients without CI a.k.a. HIV-only, and HAND). Because of the rarity of such datasets, we proposed to improve training of the multi-label classifier via a multi-domain learning scheme that also incorporates domain-specific classi-fiers on auxiliary single-label datasets specific to either binary label. Specifically, we complement the training dataset of MRIs of the four cohorts (Control: 156, CI-only: 335, HIV-only: 37, HAND: 145) ac-quired by the Memory and Aging Center at the University of California -San Francisco with a CI-specific dataset only containing MRIs of HIV-negative subjects (Controls: 229, CI-only: 397) from the Alzheimer's Disease Neuroimaging Initiative and an HIV-specific dataset (Controls: 75, HIV-only: 75) provided by SRI International. Based on cross-validation on the UCSF dataset, the multi-domain and multi-label learning strategy leads to superior classification accuracy compared with one-domain or multi-class learning ap-proaches, specifically for the undersampled HIV-only cohort. The 'prediction logits' of CI computed by the multi-label formulation also successfully stratify motor performance among the HIV-positive subjects (including HAND). Finally, brain patterns driving the subject-level predictions across all four cohorts char-acterize the independent and compounding effects of HIV and CI in the HAND cohort. (c) 2021 Elsevier B.V. All rights reserved.