Journal of Alzheimer’s Disease 66 (2018) 127–138 DOI 10.3233/JAD-180450 IOS Press 127 Effectiveness of a Personalized Brain-Computer Interface System for Cognitive Training in Healthy Elderly: A Randomized Controlled Trial Si Ning Yeo a,* , Tih Shih Lee a , Wei Theng Sng a , Min Quan Heo a , Dianne Bautista b , Yin Bun Cheung c , Hai Hong Zhang d , Chuanchu Wang d , Zheng Yang Chin d , Lei Feng e , Juan Zhou a , Mei Sian Chong f , Tze Pin Ng e , K. Ranga Krishnan g and Cuntai Guan h a Neuroscience And Behavioral Disorders Program, Duke-National University of Singapore Medical School, Singapore b Singapore Clinical Research Institute (SCRI), Singapore c Centre for Quantitative Medicine, Duke-National University of Singapore Medical School, Singapore d Institute for Infocomm Research (I²R), Agency for Science, Technology and Research (A*STAR), Singapore e Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore f Geriatric Education and Research Institute, Ministry of Health, Singapore g Department of Psychiatry, Rush Medical College, USA h School of Computer Science and Engineering, Nanyang Technological University (NTU), Singapore Handling Associate Editor: Olivia K¨ uster Accepted 5 August 2018 Abstract. Background: Cognitive training has been demonstrated to improve cognitive performance in older adults. To date, no study has explored personalized training that targets the brain activity of each individual. Objective: This is the first large-scale trial that examines the usefulness of personalized neurofeedback cognitive training. Methods: We conducted a randomized-controlled trial with participants who were 60–80 years old, with Clinical Dementia Rating (CDR) score of 0–0.5, Mini-Mental State Examination (MMSE) score of 24 and above, and with no neuropsychi- atric diagnosis. Participants were randomly assigned to the Intervention or Waitlist-Control group. The training system, BRAINMEM, has attention, working memory, and delayed recall game components. The intervention schedule comprised 24 sessions over eight weeks and three monthly booster sessions. The primary outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score after the 24-session training. Results: There were no significant between-subjects differences in overall cognitive performance post-intervention. However, a sex moderation effect (p = 0.014) was present. Men in the intervention group performed better than those in the waitlist group (mean difference, +4.03 (95% CI 0.1 to 8.0), p = 0.046. Among females, however, both waitlist-control and intervention participants improved from baseline, although the between-group difference in improvement did not reach significance. BRAINMEM also received positive appraisal and intervention adherence from the participants. * Correspondence to: Si Ning Yeo, Neuroscience and Behav- ioral Disorders Program, Duke-National University of Singapore Medical School, Khoo Teck Puat Building, 8 College Road, Level 6, Singapore 169857. Tel.: +1 416 854 7741; E-mail: yeosining@gmail.com. ISSN 1387-2877/18/$35.00 © 2018 – IOS Press and the authors. All rights reserved