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

doi:10.1016/j.ajcnut.2023.12.011

Meta-Analysis

. 2024 Mar;119(3):692-701.

doi: 10.1016/j.ajcnut.2023.12.011. Epub 2024 Jan 18.

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

Affiliations

¹ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: cvyas@mgb.org.
² Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
³ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁴ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States; Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
⁶ Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States; Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
⁷ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
⁸ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States; Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
⁹ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: Olivia.Okereke@mgh.harvard.edu.

PMID: 38244989
PMCID: PMC11103094 (available on 2025-01-18)
DOI: 10.1016/j.ajcnut.2023.12.011

Meta-Analysis

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

Chirag M Vyas et al. Am J Clin Nutr. 2024 Mar.

. 2024 Mar;119(3):692-701.

doi: 10.1016/j.ajcnut.2023.12.011. Epub 2024 Jan 18.

Authors

Affiliations

¹ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: cvyas@mgb.org.
² Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
³ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁴ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States; Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
⁶ Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States; Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
⁷ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
⁸ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States; Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
⁹ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: Olivia.Okereke@mgh.harvard.edu.

PMID: 38244989
PMCID: PMC11103094 (available on 2025-01-18)
DOI: 10.1016/j.ajcnut.2023.12.011

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: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition.

Methods: COSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472).

Results: In COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD 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 or attention [mean difference (95% CI) = 0.04 SU (-0.04, 0.11)]. The meta-analysis of COSMOS substudies 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]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y.

Conclusions: In COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits 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. This trial was registered at COSMOS-clinicaltrials.gov as NCT02422745, at COSMOS-Mind-clinicaltrials.gov as NCT03035201, and at COSMOS-Web-clinicaltrials.gov as NCT04582617.

Keywords: cognition; geriatric; meta-analysis; multivitamin-multimineral supplementation; randomized clinical trial.

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References

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1. Grodstein F., O'Brien J., Kang J.H., Dushkes R., Cook N.R., Okereke O., et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann. Intern. Med. 2013;159(12):806–814. doi: 10.7326/0003-4819-159-12-201312170-00006. - DOI - PMC - PubMed

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[1] Colby S.L., Ortman J.M. U.S. Census Bureau; Washington, DC: 2014. Projections of the Size and Composition of the U.S. Population: 2014 to 2060, Current Population Reports, P25-1143.

[2] Colby S.L., Ortman J.M. U.S. Census Bureau; Washington, DC: 2014. Projections of the Size and Composition of the U.S. Population: 2014 to 2060, Current Population Reports, P25-1143.

[3] Alzheimer’s Association Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19(4):1598–1695. 2023. - PubMed

[4] Alzheimer’s Association Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19(4):1598–1695. 2023. - PubMed

[5] Linn R.T., Wolf P.A., Bachman D.L., Knoefel J.E., Cobb J.L., Belanger A.J., et al. The 'preclinical phase' of probable Alzheimer's disease. a 13-year prospective study of the Framingham cohort. Arch. Neurol. 1995;52(5):485–490. doi: 10.1001/archneur.1995.00540290075020. - DOI - PubMed

[6] Linn R.T., Wolf P.A., Bachman D.L., Knoefel J.E., Cobb J.L., Belanger A.J., et al. The 'preclinical phase' of probable Alzheimer's disease. a 13-year prospective study of the Framingham cohort. Arch. Neurol. 1995;52(5):485–490. doi: 10.1001/archneur.1995.00540290075020. - DOI - PubMed

[7] Small B.J., Fratiglioni L., Viitanen M., Winblad B., Bäckman L. The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample. Arch. Neurol. 2000;57(6):839–844. doi: 10.1001/archneur.57.6.839. - DOI - PubMed

[8] Small B.J., Fratiglioni L., Viitanen M., Winblad B., Bäckman L. The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample. Arch. Neurol. 2000;57(6):839–844. doi: 10.1001/archneur.57.6.839. - DOI - PubMed

[9] Grodstein F., O'Brien J., Kang J.H., Dushkes R., Cook N.R., Okereke O., et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann. Intern. Med. 2013;159(12):806–814. doi: 10.7326/0003-4819-159-12-201312170-00006. - DOI - PMC - PubMed

[10] Grodstein F., O'Brien J., Kang J.H., Dushkes R., Cook N.R., Okereke O., et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann. Intern. Med. 2013;159(12):806–814. doi: 10.7326/0003-4819-159-12-201312170-00006. - DOI - PMC - PubMed

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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

Affiliations

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

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