Comorbid HIV and Cocaine Use Exacerbate Accelerated Brain Aging

Area of Science:

• Neuroscience
• Neuroimaging
• Aging Research

Background:

• Human Immunodeficiency Virus (HIV) infection and cocaine use (CU) are independently associated with cognitive deficits and brain abnormalities.
• The combined impact of HIV and CU on brain aging and cognitive function remains incompletely understood.

Purpose of the Study:

• To investigate the relationship between comorbid HIV and CU and accelerated brain aging.
• To examine how the brain age gap (BAG) relates to neurocognitive impairment (NCI) in individuals with HIV and/or CU.
• To identify specific brain structural changes associated with comorbid HIV and CU.

Main Methods:

• Trained a morphometry-based brain-age model using Gaussian Process Regression on Human Connectome Project-Aging (HCP-A) data.
• Applied the model to an independent cohort with varying HIV/CU burden (HIV-/CU-, one disorder, HIV+/CU+).
• Analyzed brain age gap (BAG) in relation to comorbidity burden and NCI, controlling for covariates; used SHapley Additive exPlanation (SHAP) for network-level analysis.

Main Results:

• A dose-dependent effect of comorbidity burden on BAG was observed, with the HIV+/CU+ group exhibiting the largest BAG.
• Increased BAG was significantly associated with a higher likelihood of NCI.
• BAG partially mediated the association between comorbidity burden and NCI, with a stronger effect in the dual-disorder group.

Conclusions:

• Comorbid HIV and CU are associated with accelerated structural brain aging.
• The brain age gap may serve as a biomarker for brain alterations linking comorbid HIV/CU to cognitive impairment.
• Identifying network-specific contributions to BAG could inform targeted interventions for individuals with comorbid HIV and CU.