To identify subgroups who may be more likely to respond well to a multidomain intervention among older adults with type 2 diabetes.

This study was a secondary analysis of the Japan Multimodal Intervention Trial for Prevention of Dementia. A total 531 participants aged 65–85 years with mild cognitive impairment were randomized into intervention (vascular risk management, exercise, nutritional counseling, and cognitive training) and control (health-related information) groups. The outcome was the change in average Z scores of neuropsychological tests from baseline to 18 months. Interactions between intervention and age (65–74, 75–85 years), memory impairment (amnestic, nonamnestic), HbA1c levels (within, outside target range), or APOE genotype (0, ≥1 APOE ε4 alleles) among participants with diabetes were evaluated using the mixed‐effects model for repeated measures.

Among 76 participants with diabetes, a significant age × intervention interaction ( P = 0.007) was found, which was driven by benefits in the younger age group (Z score difference: 0.33, 95% CI: 0.09 to 0.55) that were not observed in the older age group. Intervention benefits were also detected in those with HbA1c levels outside the target range (Z score difference: 0.31, 95% CI: 0.06 to 0.56), with HbA1c levels × intervention interaction ( P = 0.021). No significant interactions were detected between intervention and memory impairment or APOE genotype.

Multidomain interventions may benefit younger older adults or those with overly strict or lenient HbA1c control; however, these findings need confirmation in future studies.