Year: 2026
Type: preprint
Abstract: Background: HIV and cocaine use (CU) each relate to cognitive deficits and brain abnormalities, yet their combined impact on brain aging remains unclear. This study examined how comorbid HIV and CU relate to brain aging and cognitive impairment. Methods: We trained a morphometry-based brain-age model using harmonized Human Connectome Project-Aging data (HCP-A; n=725) with Gaussian Process Regression. The model was applied to an independent cohort with varying HIV/CU burden (HIV-/CU-, n=34; one disorder [HIV+/CU- or HIV-/CU+], n=72; HIV+/CU+, n=80). Brain age gap (BAG; predicted minus chronological age) was examined in relation to comorbidity burden and neurocognitive impairment (NCI; NIH Toolbox), adjusting for age, sex, education, depression, and image-quality indices. Analyses on SHapley Additive exPlanation (SHAP) values characterized network-wise feature-level contributions to brain age estimates. Results: A dose-dependent effect of comorbidity burden on BAG was observed, with the HIV+/CU+ group showing the highest BAG. Greater BAG was associated with increased likelihood of NCI, and BAG partially mediated the relationship between comorbidity burden and NCI, with a stronger mediation effect in the two-disorder group than in the one-disorder group. Structural contributors to elevated BAG in the HIV/CU cohort included cortical thickness in the visual, ventral attention, and frontoparietal networks, and sulcal depth in the sensorimotor network. Conclusion: Comorbid HIV/CU is linked to accelerated structural brain aging. BAG may reflect brain-level alterations underlying the association between comorbid HIV/CU and cognitive impairment, and may help identify network-specific targets for intervention.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Changes in Coronary Noncalcified Volume in Relation to Changes in Cocaine Use, G227026091, The Impact of Cocaine Abstinence or Reduced Use on Radiomic Features of Noncalcified Coronary Plaques in HIV-Infected Cocaine Users with Silent Coronary Artery Disease, Subclinical Atherosclerosis in HIV plus Black Cocaine Users, HIV Infection, Cocaine Use and Coronary Artery Disease in HIV+ African Americans, HIV, Cocaine & Regional Left Ventricular Dysfunction, Mapping the Human Connectome During Typical Aging, G9000095287, G9000190588, G9000205293, G9000276611
OpenAlex ID: W7128472774