{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:21:07Z","timestamp":1770942067343,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,9]]},"group-title":"Neuroscience","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Intramural Research Program, National Institutes of Health","award":["ZIADA000649"],"award-info":[{"award-number":["ZIADA000649"]}]},{"name":"National Institute on Drug Abuse, National Institutes of Health","award":["U01DA040325"],"award-info":[{"award-number":["U01DA040325"]}]},{"name":"National Institute on Drug Abuse, National Institutes of Health","award":["R01DA12777"],"award-info":[{"award-number":["R01DA12777"]}]},{"name":"National Institute on Drug Abuse, National Institutes of Health","award":["R01DA15020"],"award-info":[{"award-number":["R01DA15020"]}]},{"name":"National Institute on Drug Abuse, National Institutes of Health","award":["R01DA25524"],"award-info":[{"award-number":["R01DA25524"]}]},{"name":"National Institute on Drug Abuse, National Institutes of Health","award":["R01DA035632"],"award-info":[{"award-number":["R01DA035632"]}]},{"name":"National Institute on Drug Abuse, National Institutes of Health","award":["R21DA048780"],"award-info":[{"award-number":["R21DA048780"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We trained a morphometry-based brain-age model using harmonized Human Connectome Project\u2013Aging data (HCP-A; n=725) with Gaussian Process Regression. The model was applied to an independent cohort with varying HIV\/CU burden (HIV\u2212\/CU\u2212, n=34; one disorder [HIV+\/CU\u2212 or HIV\u2212\/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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.06.704435","type":"posted-content","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T05:55:31Z","timestamp":1770702931000},"source":"Crossref","is-referenced-by-count":0,"title":["Comorbid HIV and Cocaine Use Exacerbate Accelerated Brain Aging"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6496-0383","authenticated-orcid":false,"given":"Hong","family":"Gu","sequence":"first","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1699-9333","authenticated-orcid":false,"given":"Betty Jo","family":"Salmeron","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1071-0888","authenticated-orcid":false,"given":"Danni","family":"Wang","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Radiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"},{"name":"Institute of Human Virology, University of Maryland School of Medicine, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5632-2521","authenticated-orcid":false,"given":"Nanyu","family":"Kuang","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-9609","authenticated-orcid":false,"given":"Shenghan","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Maryland, USA"},{"name":"Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1035-5038","authenticated-orcid":false,"given":"Yihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026021215501656000_2026.02.06.704435v1.1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010752"},{"key":"2026021215501656000_2026.02.06.704435v1.2","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617702813212"},{"key":"2026021215501656000_2026.02.06.704435v1.3","doi-asserted-by":"crossref","first-page":"101310","DOI":"10.1016\/j.arr.2021.101310","article-title":"Association of HIV infection and cognitive impairment in older adults: A meta-analysis","volume":"68","year":"2021","journal-title":"Ageing Research Reviews"},{"key":"2026021215501656000_2026.02.06.704435v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32834695fb"},{"issue":"10","key":"2026021215501656000_2026.02.06.704435v1.5","first-page":"844","article-title":"Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol","volume":"3","year":"2018","journal-title":"Substance Use, and Hepatitis C Coinfection. 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