Howard A. Fink, MD, MPH; Eric Jutkowitz, PhD; J. Riley McCarten, MD; Laura S. Hemmy, PhD; Mary Butler, PhD, MBA; Heather Davila, MPA; Edward Ratner, MD; Collin Calvert, MPH; Terry R. Barclay, PhD; Michelle Brasure, PhD, MSPH, MLIS; Victoria A. Nelson, MSc; Robert L. Kane, MD †
Disclaimer: Findings and conclusions are those of the authors, who are responsible for the article's contents; findings and conclusions do not necessarily represent the views of AHRQ. No statement in this report 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: Dr. Jutkowitz reports a contract with AHRQ during the conduct of the study. Drs. Hemmy and Barclay report grant support from AHRQ during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1529.
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/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2202. Statistical code: Not applicable. Data set: See Systematic Review Data Repository at https://srdr.ahrq.gov/.
Requests for Single Reprints: Howard A. Fink, MD, MPH, VA Health Care System, One Veterans Drive, 11-G, Minneapolis, MN 55417; e-mail, Howard.email@example.com.
Current Author Addresses: Drs. Fink, McCarten, Hemmy, and Ratner: Geriatric Research Education and Clinical Center, VA Health Care System, One Veterans Drive, 11-G, Minneapolis, MN 55417.
Dr. Jutkowitz: Brown University, School of Public Health, Box G-S121-6, 121 South Main Street, 6th Floor, Providence, RI 02912.
Drs. Butler and Brasure, Ms. Davila, and Ms. Nelson: Division of Health Policy and Management, University of Minnesota, 420 Delaware Street Southeast, Mayo Memorial Building D351, Minneapolis, MN 55455.
Mr. Calvert: Division of Epidemiology, University of Minnesota, 1300 South 2nd Street, Room 300, West Bank Office Building, Minneapolis, MN 55454.
Dr. Barclay: Department of Neurology, University of Minnesota, 295 Phalen Boulevard, Mailstop 41203C, St. Paul, MN 55130.
Author Contributions: Conception and design: H.A. Fink, J.R. McCarten, L.S. Hemmy, M. Butler, M. Brasure, R.L. Kane.
Analysis and interpretation of the data: H.A. Fink, E. Jutkowitz, J.R. McCarten, L.S. Hemmy, M. Butler, H. Davila, E. Ratner, C. Calvert, T.R. Barclay, M. Brasure, V.A. Nelson, R.L. Kane.
Drafting of the article: H.A. Fink, E. Jutkowitz, L.S. Hemmy, M. Butler, H. Davila, C. Calvert, T.R. Barclay, M. Brasure, V.A. Nelson.
Critical revision of the article for important intellectual content: H.A. Fink, E. Jutkowitz, J.R. McCarten, L.S. Hemmy, M. Butler, T.R. Barclay, R.L. Kane.
Final approval of the article: H.A. Fink, E. Jutkowitz, J.R. McCarten, L.S. Hemmy, M. Butler, H. Davila, E. Ratner, C. Calvert, T.R. Barclay, M. Brasure, V.A. Nelson.
Provision of study materials or patients: M. Brasure.
Statistical expertise: H.A. Fink.
Obtaining of funding: H.A. Fink, M. Butler.
Administrative, technical, or logistic support: H. Davila, M. Brasure, V.A. Nelson.
Collection and assembly of data: H.A. Fink, E. Jutkowitz, M. Butler, H. Davila, C. Calvert, M. Brasure, V.A. Nelson.
Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain.
To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI.
Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations.
English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes.
Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy.
Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen–progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen–progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism).
High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication.
Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI.
Agency for Healthcare Research and Quality.
Fink HA, Jutkowitz E, McCarten JR, Hemmy LS, Butler M, Davila H, et al. Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018;168:39–51. doi: 10.7326/M17-1529
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Published: Ann Intern Med. 2018;168(1):39-51.
Published at www.annals.org on 19 December 2017
Cardiology, Coronary Risk Factors, Endocrine and Metabolism, Hypertension, Nephrology.
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