JMIR Publications

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 (PWH) despite antiretroviral therapy. The BrainBaseline Assessment of Cognition and Everyday Functioning (BRACE) is a validated tablet-based screener for cognition in PWH. Preliminary pilot norms were established in a small sample (n=144), but full regression-based normative data have not been developed. Consequently, HIV serostatus differences based on standardized BRACE scores and cognitive correlates have not been systematically examined.

Objective:

To develop regression-based normative data for BRACE performance in people without HIV (PWoH) who were demographically and behaviorally comparable to PWH 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 2,937 participants (1063 PWoH [499 women] and 1,874 PWH [1,053 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 Trail Making Test (A&B), Stroop-Color, and Visual-Spatial Learning. Regression-based norms were derived from PWoH using multiple demographic models (e.g., age-only, age+education, age+education+sex). The age+education model was selected for primary analyses to maximize generalizability and avoid race-based corrections. HIV serostatus and sex differences were examined using analysis of variance and chi-square tests, with effect sizes calculated using Cohen’s d.

Results:

Cognitive performance was largely comparable between PWH and PWoH across all BRACE outcome measures. Statistically significant differences were small in magnitude (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, while these associations attenuated after demographic adjustment using T-scores. Most clinical and behavioral factors (e.g., hypertension, smoking, and non-cannabis substance use) were related to poorer raw but not standardized performance. However, diabetes and cannabis use remained independently associated with T-scores across multiple measures—diabetes with poorer and cannabis use with better performance. HIV-specific clinical factors such as nadir CD4 count and ART 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 PWoH cohort and demonstrates its applicability for evaluating cognitive function in PWH. Findings indicate minimal cognitive differences between PWH and PWoH 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. Clinical Trial: NA