INTRODUCTION: We investigated the efficacy of a multidomain intervention (MI) via face-to-face and video communication platforms using a tablet personal computer application in patients with mild cognitive impairment (MCI). METHODS: Three hundred participants with MCI and ≥ 1 modifiable dementia risk factor, aged 60-85 years, were randomly assigned to either the MI group, who underwent a 24-week intervention, or the control group, who received usual care. RESULTS: The overall adherence rate to MI was 84.7%. The adjusted mean change from baseline at 24 weeks in the total scale index score of the repeatable battery for the assessment of neuropsychological status was 8.43 in the MI group and 4.26 in the control group (difference, 4.17
95% confidence interval, 1.92-6.43
p <
0.001). MI showed significant beneficial effects on cognition in both apolipoprotein E (APOE) ε4 carriers and noncarriers. DISCUSSION: MI can exert beneficial effects on the cognition of patients with MCI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05023057 HIGHLIGHTS: Although the controls also demonstrated improved performance in cognition, multidomain interventions showed significantly greater benefits for cognition in MCI compared to the controls in a randomized controlled trial. Multidomain interventions improved depression and quality of life. Multidomain interventions significantly positively impacted cognition in both APOE ε4 carriers and noncarriers. Multidomain interventions may be more effective for amnestic than nonamnestic MCI.