Japan-Multimodal Intervention Trial for the Prevention of Dementia: A randomized controlled trial

Abstract

Introduction: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI).

Methods: Participants aged 65-85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months.

Results: Of 531 participants, 406 completed the trial. The between-group difference in composite score changes was 0.047 (95% CI: -0.029 to 0.124). Secondary analyses indicated positive impacts of interventions on several secondary health outcomes. The interventions appeared to be particularly effective for individuals with high attendance during exercise sessions and those with the apolipoprotein E ε4 allele and elevated plasma glial fibrillary acidic protein levels.

Discussion: The multidomain intervention showed no efficacy in preventing cognitive decline. Further research on more efficient strategies and suitable target populations is required.

Highlights: This trial evaluated the efficacy of multidomain intervention in individuals with MCI. The trial did not show a significant difference in preplanned cognitive outcomes. Interventions had positive effects on a wide range of secondary health outcomes. Those with adequate adherence or high risk of dementia benefited from interventions.

Keywords: cognitive decline; cognitive training; dementia; diet; mild cognitive impairment; multidomain intervention; nutrition; physical exercise; randomized control trial.

FIGURE 1

Flowchart for study inclusion and exclusion.

FIGURE 2

Primary outcomes. (A) Changes in composite score from baseline to 18‐month follow‐up in full‐analysis set. (B) Changes in composite score from baseline to 18‐month follow‐up according to group‐based physical exercise session attendance rates in full‐analysis set. ^*Mean difference in changes in composite score between adherent intervention and control groups was significant (p < 0.05). ^†Mean difference in changes in composite score between adherent and non‐adherent intervention groups was significant (p < 0.05).

FIGURE 3

Changes in composite score from baseline at 18‐month follow‐up according to apolipoprotein E status in full‐analysis set. ^*Mean difference in changes in composite score between intervention and control groups was significant (p < 0.05). APOE, apolipoprotein E.

FIGURE 4

Changes in composite score from baseline at 18‐month follow‐up according to dementia‐related plasma biomarkers in full‐analysis set. ^*Mean difference in changes in composite score between intervention and control groups was significant (p < 0.05). Aβ, amyloid beta; GFAP, glial fibrillary acidic protein; NfL, neurofilament light chain; p‐tau181, tau phosphorylated at threonine 181.