Mary Butler, PhD, MBA; Victoria A. Nelson, MSc; Heather Davila, MPA; Edward Ratner, MD; Howard A. Fink, MD, MPH; Laura S. Hemmy, PhD; J. Riley McCarten, MD; Terry R. Barclay, PhD; Michelle Brasure, PhD, MSPH, MLIS; Robert L. Kane, MD †
Disclaimer: Findings and conclusions are those of the authors, who are responsible for its contents; findings and conclusions do not necessarily represent the views of AHRQ. No statement in this article should be construed as an official position of AHRQ or the U.S. Department of Health and Human Services.
Financial Support: This manuscript is based on research conducted by the Minnesota Evidence-based Practice Center under AHRQ contract 290-2015-00008-I.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1530.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at https://effectivehealthcare.ahrq.gov/topics/cognitive-decline/research-protocol. Statistical code: Not applicable. Data set: See Systematic Review Data Repository at https://srdr.ahrq.gov.
Requests for Single Reprints: Mary Butler, PhD, MBA, Division of Health Policy and Management, University of Minnesota, 420 Delaware Street Southeast, Mayo Memorial Building D351, Minneapolis, MN 55455; e-mail, email@example.com.
Current Author Addresses: Drs. Butler and Brasure, Ms. Nelson, and Ms. Davila: Division of Health Policy and Management, University of Minnesota, 420 Delaware Street Southeast, Mayo Memorial Building D351, Minneapolis, MN 55455.
Drs. Ratner, Fink, Hemmy, and McCarten: Geriatric Research Education and Clinical Center, Minneapolis VA Health Care System, One Veterans Drive, 11-G, Minneapolis, MN 55417.
Dr. Barclay: Department of Neurology, University of Minnesota, 295 Phalen Boulevard, Mailstop 41203C, St. Paul, MN 55130.
Author Contributions: Conception and design: M. Butler, H.A. Fink, L.S. Hemmy, J.R. McCarten, M. Brasure, R.L. Kane.
Analysis and interpretation of the data: M. Butler, V.A. Nelson, H. Davila, E. Ratner, H.A. Fink, L.S. Hemmy, J.R. McCarten, T.R. Barclay, M. Brasure, R.L. Kane.
Drafting of the article: M. Butler, V.A. Nelson, H. Davila, L.S. Hemmy, T.R. Barclay, R.L. Kane.
Critical revision of the article for important intellectual content: M. Butler, H. Davila, E. Ratner, H.A. Fink, L.S. Hemmy, J.R. McCarten, T.R. Barclay, M. Brasure.
Final approval of the article: M. Butler, V.A. Nelson, H. Davila, E. Ratner, H.A. Fink, L.S. Hemmy, J.R. McCarten, T.R. Barclay, M. Brasure.
Provision of study materials or patients: M. Brasure.
Obtaining of funding: M. Butler, M. Brasure, R.L. Kane.
Administrative, technical, or logistic support: V.A. Nelson, H. Davila, M. Brasure.
Collection and assembly of data: M. Butler, V.A. Nelson, H. Davila, M. Brasure.
Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain.
To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis.
Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews.
English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls.
Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.
Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported.
Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures.
Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI.
Agency for Healthcare Research and Quality.
Butler M, Nelson VA, Davila H, et al. Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018;168:52–62. [Epub ahead of print 19 December 2017]. doi: 10.7326/M17-1530
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Published: Ann Intern Med. 2018;168(1):52-62.
Published at www.annals.org on 19 December 2017
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