Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS

Abstract:

Background: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline.

Objectives: To: 1) test MVM effects on cognitive change using in-person, detailed neuropsychological assessments; 2) conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive sub-studies for a robust evaluation of MVM effects on cognition.

Design: COSMOS is a 2x2 factorial trial of cocoa extract [500 mg flavanols/day] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 US adults aged ≥60 years. There were 573 participants in the clinic sub-cohort of COSMOS (i.e., COSMOS-Clinic) who completed all cognitive tests administered at baseline. For meta-analysis, we included non-overlapping participants across three COSMOS cognitive sub-studies: COSMOS-Clinic (n=573); COSMOS-Mind (n=2158); COSMOS-Web (n=2472).

Results: In COSMOS-Clinic, we observed a modest benefit of MVM, compared to placebo, on global cognition over 2 years [mean difference (95% confidence interval (CI))=0.06 standard deviation units (SU) (-0.003, 0.13)], with a significantly more favorable change in episodic memory [mean difference (95% CI)=0.12 SU (0.002, 0.23)] but not in executive function/attention [mean difference (95% CI)=0.04 SU (-0.04, 0.11)]. Meta-analysis of COSMOS sub-studies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI)=0.07 SU (0.03, 0.11); p=0.0009] and episodic memory [mean difference (95% CI)=0.06 SU (0.03, 0.10); p=0.0007]; magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 years.

Conclusions: In COSMOS-Clinic, daily MVM supplementation led to a significantly more favorable 2-year change in episodic memory. The meta-analysis within COSMOS cognitive sub-studies indicated that daily MVM significantly benefited both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults.