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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\u2009\u00b1\u20093.78, T\u2009=\u2009\u2212\u20093.14,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.002). RTACC also showed a marginal effect on changes in brain-derived neurotrophic factor levels (beta coefficient\u2009=\u2009\u2212\u20093.13\u2009\u00b1\u20091.64,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.057). 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\u20130.84). These findings suggest that this in-game digital biomarker (RTACC) may help identify individuals likely to benefit from multi-domain intervention.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-37123-8","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T15:04:30Z","timestamp":1769785470000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developing digital biomarker for predicting cognitive response to multi-domain intervention"],"prefix":"10.1038","volume":"16","author":[{"given":"Ji Hyeun","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Sook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Hye","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jee Hyang","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Young","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoo Kyoung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Hyung","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Hyun","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Ri","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang-Rai","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"issue":"1","key":"37123_CR1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1176\/appi.focus.11.1.96","volume":"11","author":"MS Albert","year":"2013","unstructured":"Albert, M. 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S.H.C., J.H.J., S.Y.M., Y.K.P., C.H.H., and H.R.N. were investigators in the original trial and are shareholders of Rowan Inc. All clinical assessments and data collection were conducted independently by investigators at the participating hospitals. Employees of Rowan Inc. were not involved in participant recruitment, clinical assessments, data management, or outcome evaluation. J.H.J. and S.H.C. have served as consultants for PeopleBio Co. Ltd. C.H.H. has received research funding from Eisai Korea Inc., and S.H.C. is the head of Exercowork. The remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6730"}}