Developing digital biomarker for predicting cognitive response to multi-domain intervention

Abstract Computerized cognitive training allows real-time tracking of performance metrics that may serve as digital biomarkers. This study investigated the value of a novel in-game digital biomarker, RTACC (Reaction Time-Accuracy Correlation), the correlation between reaction time and accuracy, using data from 130 participants with mild cognitive impairment enrolled in the intervention arm of the SUPERBRAIN-MEET randomized controlled trial. Participants underwent a 24-week multi-domain intervention, consisting of computerized cognitive training, physical exercise, nutritional education, vascular/metabolic risk management, and motivation enhancement. RTACC was derived from task-level RT and accuracy and examined in relation to cognitive and biomarker outcomes. Linear regression analysis revealed a significant association between RTACC and changes in Repeatable Battery for the Assessment of Neuropsychological Status scores from baseline to 24 weeks (beta coefficient = -11.90 ± 3.78, T = − 3.14, P = 0.002). RTACC also showed a marginal effect on changes in brain-derived neurotrophic factor levels (beta coefficient = − 3.13 ± 1.64, P = 0.057). Logistic regression analysis demonstrated that RTACC combined with clinical information identified good responders with an area under the receiver operating characteristic curve of 0.73 (95% CI: 0.62–0.84). These findings suggest that this in-game digital biomarker (RTACC) may help identify individuals likely to benefit from multi-domain intervention.