Neurology. 2026 Aug 11;107(3):e218297. doi: 10.1212/WNL.0000000000218297. Epub 2026 Jul 20.
ABSTRACT
BACKGROUND AND OBJECTIVES: Mild cognitive impairment (MCI) is a high-risk stage for progression to dementia. The SUPERBRAIN-MEET trial previously demonstrated cognitive benefits of a multidomain lifestyle intervention (MLI) delivered through face-to-face sessions and digital platforms. The aim of this study was to examine whether the cognitive effects of the MLI varied according to sociodemographic characteristics, digital readiness, baseline cognitive status, and vascular risk profiles, in a prespecified subgroup analysis of the SUPERBRAIN-MEET randomized controlled trial.
METHODS: SUPERBRAIN-MEET was a 24-week, multicenter, outcome assessor-blinded, parallel-group randomized controlled trial conducted across 17 hospitals in South Korea. Adults aged 60-85 years with MCI were randomly assigned (1:1) to the MLI or control group. Subgroups were defined based on sociodemographic factors (sex, age, education, and living status), digital readiness (internet access, frequency of digital device use), cognitive status (MMSE score), and vascular risk profiles (body mass index [BMI], obesity status, smoking status, systolic and diastolic blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and cardiovascular comorbidity). The primary outcome was the change in the repeatable battery for the assessment of neuropsychological status (RBANS) total index score from baseline to 24 weeks. Effect modification was assessed using linear mixed-effects models with interaction terms and false discovery rate correction.
RESULTS: Of 300 randomized participants, 277 participants (mean age, 72.9 years; 69.3% female) were included in the modified intention-to-treat analysis (142 in the MLI group and 135 in the control group). MLI significantly improved RBANS total index scores compared with control at 24 weeks (between-group difference, 4.17 points; 95% CI 1.92-6.43). No subgroup interactions remained significant after false discovery rate correction, indicating consistent effects across subgroups.
DISCUSSION: In this subgroup analysis of the SUPERBRAIN-MEET trial, the cognitive benefits of MLI were not significantly modified by sociodemographic factors, digital readiness, baseline cognitive status, or vascular risk profiles. These findings should be interpreted with caution, given the exploratory nature of subgroup analyses and limited statistical power. The results support the generalizability and scalability of technology-assisted multidomain lifestyle interventions for dementia prevention in older adults with MCI.
TRIAL REGISTRATION INFORMATION: The trial was registered at ClinicalTrials.gov (NCT05023057; submitted August 20, 2021; first patient enrolled September 3, 2021; URL: clinicaltrials.gov/study/NCT05023057).
PMID:42475653 | DOI:10.1212/WNL.0000000000218297
