Associations of Multidomain Interventions With Improvements in Cognition in Mild Cognitive Impairment: A Systematic Review and Meta-analysis

Abstract

Importance: Older adults with mild cognitive impairment (MCI) have the highest risk of progressing to dementia. Evidence suggests that nonpharmacological, single-domain interventions can prevent or delay progressive declines, but it is unclear whether greater cognitive benefits arise from multidomain interventions.

Objective: To determine whether multidomain interventions, composed of 2 or more interventions, are associated with greater improvements in cognition among older adults with MCI than a single intervention on its own.

Data sources: MEDLINE, Embase, PsycInfo, AgeLine, CINAHL, and Cochrane Central Register of Controlled Trials were systematically searched from database inception to December 20, 2021.

Study selection: Included studies contained (1) an MCI diagnosis; (2) nonpharmacological, multidomain interventions that were compared with a single active control; (3) older adults aged 65 years and older; and (4) randomized clinical trials.

Data extraction and synthesis: Data were screened and extracted by 3 independent reviewers. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, random-effects meta-analyses were used to calculate effect sizes from the standardized mean difference (SMD) and 95% CIs.

Main outcomes and measures: Postintervention cognitive test scores in 7 cognitive domains were compared between single-domain and multidomain groups. Exposure to the intervention was analyzed.

Results: A total of 28 studies published between 2011 and 2021, including 2711 older adults with MCI, reported greater effect sizes in the multidomain group for global cognition (SMD, 0.41; 95% CI, 0.23-0.59; P < .001), executive function (SMD, 0.20; 95% CI, 0.04-0.36; P = .01), memory (SMD, 0.29; 95% CI, 0.14-0.45; P < .001), and verbal fluency (SMD, 0.30; 95% CI, 0.12-0.49; P = .001). The Mini-Mental State Examination (SMD, 0.40; 95% CI, 0.17-0.64; P < .001), category verbal fluency test (SMD, 0.34; 95% CI, 0.13-0.56; P = .002), Trail Making Test-B (SMD, 0.46; 95% CI, 0.13-0.80; P = .007), and Wechsler Memory Scale-Logical Memory I (SMD, 0.47; 95% CI, 0.15-0.80; P < .001) and II (SMD, 0.26; 95% CI, 0.07-0.45; P < .001) favored the multidomain group. Exposure to the intervention varied between studies: the mean (SD) duration was 71.3 (36.0) minutes for 19.8 (14.6) weeks with sessions taking place 2.5 (1.1) times per week, and all interventions lasted less than 1 year.

Conclusions and relevance: In this study, short-term multidomain interventions (<1 year) were associated with improvements in global cognition, executive function, memory, and verbal fluency compared with single interventions in older adults with MCI.

Figure 1.. Flow Diagram of Study Selection

Figure 2.. Forest Plots by Cognitive Domain

Horizontal lines indicate the 95% CIs. The size of the square data marker refers to the proportional weight of each study. The diamond represents the pooled effect size.

Figure 3.. Forest Plots of Cognitive Tests

Horizontal lines indicate the 95% CIs. The size of the square data marker refers to the proportional weight of each study. The diamond represents the pooled effect size. MMSE indicates Mini-Mental State Examination; TMT-B, Trail Making Test, Part B; and WMS-LM, Wechsler Memory Scale–Logical Memory.