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.

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.