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BrainBaseline Assessment of Cognition and Everyday Functioning (“BRACE”-ing for the Future): Establishing iPad-Based Norms for Cognitive Function in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study Combined Cohort Study

Year: 2026
Type: article
Abstract: Background: Digital cognitive assessments are increasingly used in large-scale studies to assess brain health, offering scalable, standardized, and self-directed testing solutions. Cognitive function remains a concern for people with HIV despite antiretroviral therapy. The BRACE (BrainBaseline Assessment of Cognition and Everyday Functioning) is a validated tablet-based screener for cognition in people with HIV. Preliminary pilot norms were established in a small sample (n=144), but full regression-based normative data have not yet been developed. Consequently, HIV serostatus differences based on standardized BRACE scores and cognitive correlates have not been systematically examined. Objective: This study aims to develop regression-based normative data for BRACE performance in people without HIV who were demographically and behaviorally comparable to people with HIV within biological sex; to examine differences in cognitive performance by HIV status and biological sex; and to evaluate sociodemographic, behavioral, and clinical correlates of BRACE performance. Methods: A total of 2937 participants (1063 people without HIV [499 women] and 1874 people with HIV [1053 women]) in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study completed BRACE once between November 2020 and March 2025. BRACE includes the Trail Making Test (A and B), Stroop-Color, and visual spatial learning. Regression-based norms were derived from people without HIV using multiple demographic models (eg, age-only, age + education, and age + education + sex). The age + education model was selected for primary analyses because it provided the best balance of interpretability, parsimony, and generalizability while avoiding race-based corrections. HIV serostatus and sex differences were examined using ANOVA and χ2 tests, with effect sizes calculated using Cohen's d. Results: Cognitive performance was largely comparable between people with HIV and people without HIV across all BRACE outcome measures. Statistically significant differences were very small in magnitude (all effect sizes<0.11) and primarily observed among men on Stroop-Color. Across groups, older age and fewer years of education were associated with poorer raw BRACE performance, although these associations attenuated after demographic adjustment using T-scores. Most clinical and behavioral factors (eg, hypertension, smoking, and noncannabis substance use) were related to poorer raw scores but not standardized performance. However, diabetes and cannabis use remained independently associated with T-scores across multiple measures-diabetes with poorer scores and cannabis use with higher scores, an association that should be interpreted cautiously. HIV-specific clinical factors, such as nadir CD4 count and antiretroviral therapy duration, were linked primarily to raw scores. Conclusions: This study establishes the first regression-based normative data for BRACE, derived from a large, demographically diverse people without HIV, and demonstrates its applicability for evaluating cognitive function in people with HIV. Findings indicate minimal cognitive differences between people with HIV and people without HIV and highlight the influence of common sociodemographic and metabolic factors. These results support BRACE as a scalable, reliable, and self-administered digital tool for assessing cognitive health in diverse populations and underscore its potential for longitudinal monitoring and precision phenotyping in both research and clinical contexts.
Language: English
Subfield: Virology
Open Access status: gold
Estimated APC paid: $2,750
Funders: Bill and Melinda Gates Foundation, American Heart Association, Dana Foundation, Oak Foundation, Research to Prevent Blindness, World Health Organization, UNICEF, United Nations Population Fund, Northern Illinois University, Northwestern University, Natural Science Foundation of Shanghai, University of Calgary, Conservation International, Cenovus Energy, Canadian Natural Resources Limited, Nippon Sheet Glass Foundation for Materials Science and Engineering, Horowitz Foundation for Social Policy, Suncor Energy Incorporated, Irish College of General Practitioners, BC Children’s Hospital Foundation, Vietnam Academy of Science and Technology, Waterloo Foundation, Imperial Oil Limited, UK Research and Innovation, University Grants Commission of Bangladesh, Georgia Clinical and Translational Science Alliance, University of Sharjah, National Research Foundation of Ukraine, Inselspital, Universitätsspital Bern, University of Bisha, Genome British Columbia, Cancer Research UK, Nuffield Foundation, Dunhill Medical Trust, Age UK, University of Manchester, Rosetrees Trust, National Research Foundation, Department of Science and Technology, Ministry of Science and Technology, India, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Natural Science Foundation of China, ZonMw, Bundesministerium für Bildung und Forschung, Albert-Ludwigs-Universität Freiburg, Coloplast, Fonds Wetenschappelijk Onderzoek, Ministry of Science, ICT and Future Planning, Natural Science Foundation of Hubei Province, Narodowe Centrum Nauki, Seoul National University Hospital, Universiteit Stellenbosch, Universiti Putra Malaysia, Ministry of Education, India, Foundation of Henan Educational Committee, King Mongkut's University of Technology Thonburi, Deutsches Zentrum für Neurodegenerative Erkrankungen, University of British Columbia, Centre National pour la Recherche Scientifique et Technique, Huizhou University, Natural Science Foundation of Shandong Province, King Khalid University, Majmaah University, International AIDS Society, Kao Corporation, Marmara Üniversitesi, Al-Imam Muhammad Ibn Saud Islamic University, Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen, Thailand Science Research and Innovation, Berlin University Alliance, European Society for Immunodeficiencies, National Institutes of Health, University of California, San Francisco, Center for AIDS Research, University of Alabama at Birmingham, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Japan Society for the Promotion of Science, University Natural Science Research Project of Anhui Province, National Key Research and Development Program of China, Humanities and Social Science Fund of Ministry of Education of China, Faculty of Medicine Siriraj Hospital, Mahidol University, National College Students Innovation and Entrepreneurship Training Program, Research England, Basic and Applied Basic Research Foundation of Guangdong Province, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Nursing Research, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Institute on Minority Health and Health Disparities, National Center for Complementary and Integrative Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Center for AIDS Research, University of North Carolina at Chapel Hill, Clinical and Translational Science Institute, University of California, Los Angeles, HORIZON EUROPE Widening Participation and Strengthening the European Research Area, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Google Research, Korea Forestry Promotion Institute, Intramural Research Program
Awards: G1034546755, G1296759572, Translational Biomedical Science Training Grant, G1913134163, G1972383081, Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS), G2008237588, G2435036225, G2542587862, G2840405583, G3102910958, G311558797, G3869857964, G4044828089, G409006598, G4584981698, G4844376359, G4953964255, G5147848267, G562934659, G5660189159, G5699974340, G5817808917, G5863844756, Clinical and Translational Science Institute, G5900455136, G5933640408, G6384504179, G6396423216, G6509896931, University of Miami Developmental HIV/AIDS Mental Health Research Center (D-ARC), G6745172908, G6759032351, G6809319421, G6990385686, G7001360886, G7152846654, G7454986501, Institutional Career Development Core, G7627181020, G775892330, G7760075911, G7807729167, Johns Hopkins Institute for Clinical and Translational Research, University of Pittsburgh MACS/WIHS CCS, MACS/WIHS -CCS, ERC Einstein-Rockefeller-CUNY Center for AIDS research, SF Bay Area MACS/WIHS Combined Cohort Study, UNC MACS/WIHS Combined Cohort Study Clinical Research Site, Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studies, Center for AIDS Research at Emory University, JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN), Northwestern CORE Clinical Research Site: Trans-omics for HIV/AIDS Research, Los Angeles CRS for the MACS/WIHS Combined Cohort Study, Data Analysis and Coordination Center for the MACS-WIHS Combined Cohort Study, MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS), The University of North Carolina Center for AIDS Research, MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS), Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center, Atlanta MACS/WIHS Combined Cohort Study Clinical Research Site, UAB-MISS MACS/WIHS Combined Cohort Study, Miami Center for AIDS Research, UCLA Clinical and Translational Science Institute, Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS), UAB Center for AIDS Research (CFAR), G929137571
OpenAlex ID: W7137895181
FWCI: 3.325
Cites: 16
Cited by: 1
Related to: 10