Impact of comorbidity of HIV infection and substance use disorder on brain aging and cognitive impairment

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

1. Comorbid HIV Infection and Chronic Cocaine Use Accelerate Brain Aging and Exacerbate Cognitive Impairment In this study, we investigated the combined impact of comorbid chronic cocaine exposure in people living with HIV (PLWH) on brain aging and neurocognitive impairment (NCI). A brain aging model was built based on network-wise cortical metrics in the brain MRI of Human Connectome Project in Aging (HCP-A) (N = 725, age range = 36-100 years) using a machine learning approach. The model was applied to a community cohort of HIV-infected and uninfected participants with or without cocaine use (N = 186, age range = 35-76.6 years) to predict their brain ages. Brain age gap (BAG) was defined as the difference between the predicted brain age and chronological age, with a positive BAG indicating accelerated brain aging. Cognitive performance was evaluated by NIH Toolbox cognition battery (NIHTB-CB) and NCI was defined present if the fully adjusted T scores in at least two cognitive domains was 1.0 SD below the mean. Cognitively, BAG was significant higher in participants with NCI than without NCI (p=.013). Compared with controls, PLWH showed larger BAG (p=.00061) and higher risk of NCI (OR=3.36, p=0.019). Similarly, participants who reported cocaine use showed larger BAG (p=.0031) and marginally higher risk of NCI (OR=2.80, p=0.052). Furthermore, PLWH using cocaine showed marginally significantly larger BAG (p=.088) compared to PLWH without cocaine use. When compared to HIV-uninfected participants with cocaine use, PLWH using cocaine showed larger BAG (p=.032). This study demonstrated that both HIV infection and chronic cocaine use contribute to accelerated brain aging and increased risk of neurocognitive impairment, and chronic cocaine use further exacerbates neurobiological aging in PLWH. (Presented in the STI & HIV 2025 conference) 2. HIV and Low Omega-3 Levels May Heighten Hippocampal Volume Differences Between Men and Women with Substance Use Sex differences in hippocampal volumes are well-documented, but their interaction with HIV status and omega-3 fatty acids—particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—remains unclear, especially in underserved populations. This study examines how HIV and omega-3 fatty acids influence sex differences in hippocampal volume and explores whether cognitive performance related to episodic memory modifies the association of omega-3 levels with hippocampal volume, considering both HIV status and sex. Brain MRI and clinical data on166 participants were analyzed. Brain MRIs were acquired using a 3.0-T Siemens scanner, and volumetric segmentation was conducted with FreeSurfer (version 6.0), adjusting for intracranial volume (ICV). Our study found that: (1) Among HIV-negative participants, females had significantly lower hippocampal volumes than males in 1 of 26 regions, whereas HIV-positive females had lower volumes in 13 of 26 regions (p < 0.006 for HIV-negative vs. HIV-positive females), (2) In HIV-positive individuals with EPA levels ≤0.40 %, females exhibited lower volumes in 11 of 26 regions, compared to no differences in those with EPA levels >0.40 % (p = 0.0003 for ≤0.40 % vs. >0.40 %), (3) Across all participants, lower EPA and DHA levels were associated with greater sex differences in hippocampal volumes, which diminished or disappeared at higher EPA and DHA levels (p < 0.00001 for EPA ≤0.40 % vs. >0.40 %; p = 0.004 for DHA ≤2.0 % vs. >2.0 %), and (4) Among Adults with lower episodic memory, higher log-scaled EPA levels were independently associated with greater hippocampal volume. HIV may amplify sex differences in hippocampal volumes, disproportionately affecting females. Higher EPA and DHA levels may mitigate these effects, suggesting a protective role against hippocampal atrophy. Further studies are warranted to confirm these findings and explore whether the benefits extend to males with HIV or individuals without HIV. (Lai et al., Brain, Behavior, & Immunity - Health, 2025)