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

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1. Impact of comorbidity of HIV infection and substance use disorder on cognitive impairment Collaborating with Dr. Shenghan Laigroup at the University of Maryland School of Medicine, we started investigating the impact of comorbidity of HIV infection and substance use disorder on cognitive impairment. A cohort of 922 adults, predominantly African Americans (AAs), with/without HIV and with/without cocaine use disorder (CUD) were enrolled in the study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female participants were associated with NCI, the associations were dependent on cocaine use. Specifically, neither HIV adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77-1.64 nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among participants who did not use cocaine, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in participants who used cocaine. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population. (Lai et al., AIDS Patient Care STDS, 2023) 2. Impact of comorbidity of HIV infection and substance use disorder on brain aging and functional connectivity We are using brain MRI data collected on 166 participants (out of the 922 participants above, including with/without HIV and with/without cocaine use) to investigate the impact of comorbidity of HIV infection and substance use disorder on brain aging and functional connectivity. MRI data include structural images (T1-weighted, T2-weighted, FLAIR, and T1Rho-weighted), diffusion-based images, cerebral blood flow images (arterial-spin labeling images), and resting-state functional MRI. We will estimate brain age using Brain-Age Regression Analysis and Computation Utility Software (BARACUS) in the four groups (HIV+&CUD+, HIV+&CUD-, HIV-&CUD+, HIV-&CUD-). The difference between a participants chronological age and brain-predicted age (brain age gap) will be used to assess cognitive impairment. We will examine white matter integrity and cerebral blood flow in these groups using diffusion-based MRI and cerebral blood flow MRI, respectively. Functional connectivity within and between large-scale networks relevant to cognitive functions (e.g., executive control network, default-mode network, and salience network) will be used to assess cognitive impairments in these groups.