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Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia: A Systematic Review
Comparative Effectiveness Review, No. 223
Investigators: Howard A. Fink, M.D., M.P.H., Laura S. Hemmy, Ph.D., Eric J. Linskens, B.S., Pombie C. Silverman, B.A., Roderick MacDonald, M.S., J. Riley McCarten, M.D., Kristine M.C. Talley, Ph.D., R.N., G.N.P.-B.C., FGSA, Priyanka J. Desai, M.S.P.H., Mary L. Forte, Ph.D., D.C., Margaret A. Miller, M.A., Michelle Brasure, Ph.D., M.S.P.H., M.L.I.S., Victoria A. Nelson, M.Sc., Brent C. Taylor, Ph.D., M.P.H., Weiwen Ng, M.P.H., Jeannine M. Ouellette, M.F.A., Nancy L. Greer, Ph.D., Kerry M. Sheets, M.D., Timothy J. Wilt, M.D., M.P.H., and Mary Butler, Ph.D., M.B.A.
Structured Abstract
Objective:
To summarize evidence on: (1) the accuracy of brief cognitive tests for identifying clinical Alzheimer’s-type dementia (CATD) in individuals with suspected cognitive impairment; (2) the accuracy of biomarkers for identifying Alzheimer’s disease (AD) in individuals with dementia; and (3) the benefits and harms of prescription drugs and supplements for cognition, function, and behavioral and psychological symptoms of dementia (BPSD) in patients with CATD.
Data sources:
Electronic bibliographic databases to March 2019, ClinicalTrials.gov, systematic review bibliographies.
Review methods:
Cognitive test accuracy studies must have used explicit CATD diagnostic criteria and a non-CATD control group. Biomarker accuracy studies must have used neuropathologic criteria to define AD cases and non-AD controls. All treatment trials must have enrolled participants with CATD; those evaluating BPSD enrolled individuals with CATD and BPSD. Minimum trial duration was 2 weeks for agitation, aggression, psychosis, and disinhibited sexual behavior, and 24 weeks for other outcomes. Two reviewers rated risk of bias (ROB) and strength of evidence. One reviewer extracted data; a second checked accuracy. We analyzed English-language studies with low or medium ROB.
Results:
We analyzed 56 unique studies on the accuracy of brief cognitive tests for CATD, 24 on accuracy of biomarkers for AD (15 brain imaging, nine cerebrospinal fluid [CSF] testing), and 67 trials of CATD treatment (54 reporting cognition or function, 13 reporting BPSD). Multiple brief cognitive tests were highly sensitive and specific (≥0.8) for distinguishing CATD from normal cognition, but less so for distinguishing mild CATD from normal cognition or CATD from mild cognitive impairment (MCI). Based on few studies, compared with clinical evaluation alone, amyloid positron emission tomography (PET), fluorodeoxyglucose (FDG)-PET, and combinations of CSF tests added to clinical evaluation may improve accuracy for distinguishing AD from non-AD dementia. Regardless of CATD severity, cholinesterase-inhibitors produced small improvements in cognition and function compared with placebo but may increase serious adverse events and withdrawals due to adverse events. For moderate to severe CATD, memantine plus a cholinesterase inhibitor slightly improved global change and inconsistently improved cognition, but not function, compared with a cholinesterase inhibitor alone. Evidence was mostly insufficient about the effects of prescription drugs and supplements on agitation, aggression, psychosis, or disinhibited sexual behavior.
Conclusions:
Brief cognitive tests accurately distinguished CATD from normal cognition, but were less accurate distinguishing smaller clinical differences. Whether biomarkers improve diagnostic accuracy when added to clinical evaluation needs further verification, but potential benefits of testing are limited by lack of effective treatments for AD and non-AD dementias. Cholinesterase-inhibitors slightly outperformed placebo for cognition and function, but evidence of whether any drug treatments improved BPSD was largely insufficient.
Contents
- Key Messages
- Preface
- Acknowledgments
- Key Informants
- Technical Expert Panel
- Peer Reviewers
- Evidence Summary
- Chapter 1. Introduction
- Chapter 2. Methods
- Chapter 3. Search Results
- Chapter 4. Key Question 1: Brief Cognitive Tests for Identifying CATD
- Chapter 5. Key Question 2: Biomarkers for Identifying Neuropathologically Confirmed AD
- Chapter 6. Key Question 3: Prescription Drugs Versus Placebo for Cognition, Function, and Quality of Life
- Chapter 7. Key Question 4: Supplements Versus Placebo for Cognition, Function, and Quality of Life
- Chapter 8. Key Question 5: Prescription Drugs Versus Other Active Treatments for Cognition, Function, and Quality of Life
- Chapter 9. Key Question 6: Prescription Drugs Versus Placebo for Behavioral and Psychological Symptoms of Dementia
- Chapter 10. Key Question 7: Supplements Versus Placebo for Behavioral and Psychological Symptoms of Dementia
- Chapter 11. Key Question 8: Prescription Drug Treatment Versus Other Active Treatment for Behavioral and Psychological Symptoms of Dementia
- Chapter 12. Discussion
- References
- Abbreviations
- Appendixes
- Appendix A. Search Strategy
- Appendix B. Risk of Bias Assessment Decision Aid
- Appendix C. Key Question 1: Accuracy, Comparative Accuracy, and Harms of Cognitive Tests for Identifying CATD
- Appendix D. Key Question 2: Accuracy, Comparative Accuracy, and Harms of Biomarkers for Identifying Pathologically Confirmed AD
- Appendix E. Key Question 3: Efficacy and Harms of Prescription Drug Treatment Versus Placebo for Cognition, Function, and Quality of Life
- Appendix F. Key Question 4: Efficacy and Harms of Supplements Versus Placebo for Cognition, Function, and Quality of Life
- Appendix G. Key Question 5: Comparative Effectiveness and Harms of Prescription Drug Treatment Versus Other Active Treatments for Cognition, Function, and Quality of Life
- Appendix H. Key Question 6: Efficacy and Harms of Prescription Drug Treatment Versus Placebo for Behavioral and Psychological Symptoms of Dementia
- Appendix I. Key Question 7: Efficacy and Harms of Supplements Versus Placebo for Behavioral and Psychological Symptoms of Dementia
- Appendix J. Key Question 8: Comparative Effectiveness and Harms of Prescription Drug Treatment Versus Other Active Treatment for Behavioral and Psychological Symptoms of Dementia
- Appendix K. Background Tables
- Appendix L. Excluded References
- Appendix M. Included References
Suggested citation:
Fink HA, Hemmy LS, Linskens EJ, Silverman PC, MacDonald R, McCarten JR, Talley KMC, Desai PJ, Forte ML, Miller MA, Brasure M, Nelson VA, Taylor BC, Ng W, Ouellette JM, Greer NL, Sheets KM, Wilt TJ, Butler M. Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia: A Systematic Review. Comparative Effectiveness Review No. 223. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-2015-00008-I.) AHRQ Publication No. 20-EHC003. Rockville, MD: Agency for Healthcare Research and Quality; April 2020. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER223.
This report is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00008-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders.
AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program website at www.effectivehealthcare.ahrq.gov. Search on the title of the report.
People using assistive technology may not be able to fully access information in this report. For assistance contact vog.shh.qrha@cpe.
- NLM CatalogRelated NLM Catalog Entries
- Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.[Ann Intern Med. 2020]Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.Fink HA, Linskens EJ, MacDonald R, Silverman PC, McCarten JR, Talley KMC, Forte ML, Desai PJ, Nelson VA, Miller MA, et al. Ann Intern Med. 2020 May 19; 172(10):656-668. Epub 2020 Apr 28.
- Brief Cognitive Tests for Distinguishing Clinical Alzheimer-Type Dementia From Mild Cognitive Impairment or Normal Cognition in Older Adults With Suspected Cognitive Impairment.[Ann Intern Med. 2020]Brief Cognitive Tests for Distinguishing Clinical Alzheimer-Type Dementia From Mild Cognitive Impairment or Normal Cognition in Older Adults With Suspected Cognitive Impairment.Hemmy LS, Linskens EJ, Silverman PC, Miller MA, Talley KMC, Taylor BC, Ouellette JM, Greer NL, Wilt TJ, Butler M, et al. Ann Intern Med. 2020 May 19; 172(10):678-687. Epub 2020 Apr 28.
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- Accuracy of Biomarker Testing for Neuropathologically Defined Alzheimer Disease in Older Adults With Dementia.[Ann Intern Med. 2020]Accuracy of Biomarker Testing for Neuropathologically Defined Alzheimer Disease in Older Adults With Dementia.Fink HA, Linskens EJ, Silverman PC, McCarten JR, Hemmy LS, Ouellette JM, Greer NL, Wilt TJ, Butler M. Ann Intern Med. 2020 May 19; 172(10):669-677. Epub 2020 Apr 28.
- Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia: A Systematic Revi...Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia: A Systematic Review
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