PREVENTING COGNITIVE DECLINE
AND DEMENTIA
A WAY FORWARD
Committee on Preventing Dementia and Cognitive Impairment
Alan I. Leshner, Story Landis, Clare Stroud, and Autumn Downey,
Editors
Board on Health Sciences Policy
Health and Medicine Division
A Consensus Study Report of
THE NATIONAL ACADEMIES PRESS
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This activity was supported by Contract No. HHSN26300074 with the U.S. Department of Health and Human Services’ National Institutes of Health through the National Institute on Aging. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-45959-4
International Standard Book Number-10: 0-309-45959-1
Digital Object Identifier: https://doi.org/10.17226/24782
Library of Congress Control Number: 2017950614
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2017. Preventing cognitive decline and dementia: A way forward. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24782.
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COMMITTEE ON PREVENTING DEMENTIA AND COGNITIVE IMPAIRMENT
ALAN I. LESHNER (Chair), CEO Emeritus, American Association for the Advancement of Science
STORY LANDIS (Vice Chair), Director Emerita, National Institute of Neurological Disorders and Stroke
MARILYN ALBERT, Professor of Neurology, Director of the Division of Cognitive Neuroscience, Johns Hopkins University School of Medicine
LISA L. BARNES, Professor of Neurological Sciences and Behavioral Sciences, Director of the Rush Center of Excellence on Disparities in HIV and Aging, Rush University Medical Center
DAN G. BLAZER, J.P. Gibbons Professor of Psychiatry Emeritus, Duke University Medical Center
MARK A. ESPELAND, Professor of Biostatistical Sciences, Wake Forest School of Medicine
J TAYLOR HARDEN, Executive Director, National Hartford Center of Gerontological Nursing Excellence
CLAUDIA H. KAWAS, Professor of Neurology, Professor of Neurobiology and Behavior, University of California, Irvine
NAN M. LAIRD, Harvey V. Fineberg Research Professor of Public Health, Harvard University
KENNETH M. LANGA, Cyrus Sturgis Professor of Medicine, University of Michigan and Veterans Affairs Ann Arbor Healthcare System
ERIC B. LARSON, Vice President, Research and Health Care Innovation, Kaiser Foundation Health Plan of Washington
JOSÉ A. LUCHSINGER, Florence Irving Associate Professor of Medicine, Associate Professor of Epidemiology, Columbia University
RONALD C. PETERSEN, Professor of Neurology, Cora Kanow Professor of Alzheimer’s Disease Research, Mayo Clinic College of Medicine
RALPH L. SACCO, Professor and Olemberg Chair of Neurology, Executive Director of the McKnight Brain Institute, University of Miami; Chief of Neurology, Jackson Memorial Hospital
SUDHA SESHADRI, Professor of Neurology, Boston University School of Medicine
LESLIE B. SNYDER, Professor of Communication, University of Connecticut
KRISTINE YAFFE, Professor of Psychiatry, Neurology, and Epidemiology and Biostatistics, Vice Chair for Clinical and Translational Research, Roy and Marie Scola Endowed Chair, University of California, San Francisco
Study Staff
CLARE STROUD, Study Director (until April 2017)
AUTUMN DOWNEY, Study Director (since April 2017)
SHEENA M. POSEY NORRIS, Program Officer
BENJAMIN KAHN, Research Associate
OLIVIA YOST, Research Associate
DANIEL FLYNN, Senior Program Assistant
ANDREW POPE, Director, Board on Health Sciences Policy
National Academy of Medicine Gilbert S. Omenn Fellow
JAMES BURKE, Assistant Professor of Neurology, University of Michigan Medical School
Consultants
LISA BAIN, Consultant Writer
RONA BRIERE, Senior Editor, Briere Associates, Inc.
REVIEWERS
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
Carol Brayne, University of Cambridge
Steven T. DeKosky, University of Florida College of Medicine
Rebecca Gottesman, Johns Hopkins University School of Medicine
Francine Grodstein, Brigham and Women’s Hospital
David E. Housman, Massachusetts Institute of Technology
Caryn Lerman, University of Pennsylvania
Roger J. Lewis, Harbor-UCLA Medical Center
Martha C. Morris, Rush Medical College
Brenda Plassman, Duke University Medical Center
Patricia Reuter-Lorenz, University of Michigan
Mary Sano, Icahn School of Medicine at Mount Sinai and the James Peters Veterans Affairs Medical Center
Shekhar Saxena, World Health Organization
Brian Southwell, RTI International
William Thies, Alzheimer’s Association
Joe Verghese, Albert Einstein College of Medicine
Keith E. Whitfield, Wayne State University
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by Enriqueta C. Bond, Burroughs Wellcome Fund, and Huda Akil, University of Michigan. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
PREFACE
The prospect of potential cognitive decline and the development of dementia is a significant source of anxiety for many people as they age, raising deep concerns about their future independence and quality of life. Yet for those interested in taking active steps to maintain, to the extent possible, their brain health, it is difficult to know how best to invest their time and resources. A bewildering number of products and behaviors have been touted as potential preventive measures, but very few have been subjected to rigorous testing for effectiveness. Recognizing that many people turn to the National Institute on Aging (NIA) of the National Institutes of Health for up-do-date information on both normal cognitive decline and neuropathological processes that can occur with aging, NIA asked the National Academies of Sciences, Engineering, and Medicine to convene a committee to examine and comment on the state of knowledge about what works in preventing or slowing cognitive decline and dementia.
This report examines the current state of the evidence on interventions for preventing cognitive decline and dementia and is intended to inform future efforts to develop public health strategies and messages, as well as to suggest future research priorities for improving the quality of the relevant knowledge base. Although the evidence has not yet matured to the level that would support an assertive public health campaign aimed at widespread adoption of any such intervention, the report does identify those interventions, supported by some evidence of benefit, that the committee believes should be discussed with members of the public who are actively seeking advice on steps they can take to maintain brain health as they age. Two key points add important context to the committee’s recommendations.
First, the committee was asked to make its recommendations based largely on the most stringent form of evidence—randomized controlled trials (RCTs). RCTs are the gold standard in evidence generation but require large investments of money and time. Moreover, while they are particularly effective for testing single-intervention solutions, the apparent complexity of the pathophysiology underlying cognitive decline and dementia suggests that a multifaceted approach may be most effective. Such an approach is challenging to evaluate through an RCT. To lend confidence to the suggestions emerging from RCTs, then, the committee considered other salient sources of evidence that, when combined with RCT-based evidence, offer a fuller picture.
Second, it should be emphasized that the committee’s analysis is of necessity based on the current state of knowledge, and addresses a rapidly evolving scientific field. Fundamental understanding of the processes of cognitive decline and dementia is advancing at an impressive pace. Moreover, additional intervention studies were being conducted even as this report was being written, and they are expected to yield important insights. The committee’s suggestions for prioritizing future research, including methodological recommendations, are intended to help shape future research efforts in this domain and generate a more comprehensive and stronger evidence base.
We wish to offer our deep gratitude to the members of this National Academies of Sciences, Engineering, and Medicine committee. Leading such an expert and committed group of scholars, all of whom gave generously of their time, has been an incredibly rewarding experience. This work also benefited greatly from the exceptional competence and dedication of the National Academies staff and many others cited in the acknowledgments that follow.
Alan I. Leshner, Chair
Story Landis, Vice Chair
Committee on Preventing Dementia and Cognitive Impairment
ACKNOWLEDGMENTS
The committee first would like to recognize and honor the contributions of Robert Lewis Kane to this project. Dr. Kane led the work of the Minnesota Evidence-based Practice Center to develop the Agency for Healthcare Research and Quality (AHRQ) systematic review that formed the primary evidence base used by the committee. His leadership and deep knowledge in this area were critical to the development of this extensive, thorough, and thoughtful analysis of interventions for cognitive decline and dementia. Sadly, Dr. Kane died unexpectedly while the committee was writing this report. Dr. Kane was the Minnesota Chair of Aging and Long-Term Care at the University of Minnesota’s School of Public Health, where he had a long and productive career. He was known for his scholarship, his deeply felt advocacy to help individuals age with grace and dignity, his generosity to colleagues and students, and his sense of humor. Among many other important contributions, his work with the Office of Technology Assessment’s Advisory Committee on Alzheimer’s Disease and Related Disorders helped put Alzheimer’s disease “on the map” from the perspective of research, clinical care, and policy. He was a true force in the field and will be greatly missed.
The committee also acknowledges and thanks the study sponsor—the National Institute on Aging—and particularly Richard Hodes, Marie A. Bernard, and Melinda Kelley for their leadership and vision in the development of this project. We are grateful to David Niebuhr, Kim Wittenberg, and colleagues at AHRQ for overseeing the systematic review that formed the primary evidence base used for the study. We also wish to recognize and thank Mary Butler, Howard Fink, and the many others at the Minnesota
Evidence-based Practice Center who worked with Dr. Kane on the preparation of the AHRQ systematic review.
We wish to express our gratitude to the many individuals who gave presentations to and participated in discussions with the committee. We especially thank Walter Koroshetz (National Institute of Neurological Disorders and Stroke) and William Thies (Alzheimer’s Association) for sharing their insights with the committee during the initial phase of the project, as well as the following workshop presenters: James Appleby (Gerontological Society of America), Matthew Baumgart (Alzheimer’s Association), Michael Ellenbogen (Alzheimer’s disease/dementia advocate), Mary Ann Forciea (University of Pennsylvania and American College of Physicians), Rebecca Gottesman (Johns Hopkins University), Stacy Pagos Haller (BrightFocus Foundation), Julene Johnson (University of California, San Francisco), Brian LeBlanc (Alzheimer’s disease advocate), Sarah Lenz Lock (AARP), Susan McCurry (University of Washington), Regina Davis Moss (American Public Health Association), Edo Richard (Radboud University), Walter Rocca (Mayo Clinic), Mary Sano (Mount Sinai School of Medicine), Lisa Shulman (University of Maryland and American Academy of Neurology), Brian Southwell (RTI International), Joe Verghese (Albert Einstein College of Medicine), Jeff Williamson (Wake Forest Baptist Health), and Sherry Willis (University of Washington).
Finally, the committee would like to express its gratitude to and admiration for the National Academies of Sciences, Engineering, and Medicine staff who worked so hard and so well on the study: Clare Stroud, Autumn Downey, Sheena Posey Norris, Benjamin Kahn, Olivia Yost, and Daniel Flynn. We also are grateful for the contributions of James Burke, Gilbert S. Omenn Fellow at the National Academy of Medicine; Rona Briere, for her careful editing of the report; and Rebecca Morgan of the National Academies Research Center, for her assistance with fact-checking.
Identify Individuals Who Are at Higher Risk of Cognitive Decline and Dementia
Increase Participation of Underrepresented Populations in Intervention Trials
Begin More Interventions at Younger Ages and Have Longer Follow-Up Periods
Use Consistent Cognitive Outcome Measures Across Trials to Enable Pooling
Integrate Robust Cognitive Outcome Measures into Trials with Other Primary Purposes
Include Biomarkers as Intermediate Outcomes
Conduct Large Trials in Routine Clinical Practices or Community Settings
4 PRIORITIES FOR FUTURE RESEARCH
Cross-Cutting Intervention Design Considerations
Lowest-Priority Interventions for Future Research
A Agency for Healthcare Research and Quality (AHRQ) Systematic Review
ACRONYMS AND ABBREVIATIONS
ACCORD-MIND |
Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes trial |
ACE |
angiotensin converting enzyme |
AChEI |
acetylcholinesterase inhibitor |
ACTIVE |
Advanced Cognitive Training for Independent and Vital Elderly trial |
ADAS-Cog |
Alzheimer’s Disease Assessment Scale-Cognitive Subscale |
ADRD |
Alzheimer’s disease-related dementias |
ADVANCE |
Action in Diabetes and Vascular Disease: PreterAx and DiamicroN-MR Controlled Evaluation trial |
AHRQ |
Agency for Healthcare Research and Quality |
ARB |
angiotensin receptor blockers |
ARCD |
age-related cognitive decline |
BDNF |
brain-derived neurotrophic factor |
CATD |
clinical Alzheimer’s-type dementia |
CBTI |
cognitive-behavioral therapy for insomnia |
CFAS |
Cognitive Function and Ageing Study |
CI |
confidence interval |
COX-2 |
cyclooxygenase-2 |
DASH |
Dietary Approaches to Stop Hypertension |
EPC |
evidence-based practice center |
EXERT |
Exercise in Adults with Mild Memory Problems trial |
FINGER |
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability |
GRADE |
Glycemic Reduction Approaches in Diabetes trial |
HOPE-3 |
Heart Outcomes Prevention Evaluation-3 |
HRS |
Health and Retirement Study |
HYVET |
Hypertension in the Very Elderly Trial |
IADL |
instrumental activity of daily living |
IHAMS |
Iowa Health and Active Minds Study |
IOM |
Institute of Medicine |
LIFE |
Lifestyle Interventions and Independence for Elders trial |
MAPT |
Multidomain Alzheimer’s Prevention Trial |
MAX |
Mental Activity and Exercise trial |
MCI |
mild cognitive impairment |
MIND |
Mediterranean-DASH Intervention for Neurodegenerative Delay |
MMSE |
Mini Mental State Exam |
NIA |
National Institute on Aging |
NIH |
National Institutes of Health |
NMDA |
N-methyl-D-aspartate |
NSAID |
nonsteroidal anti-inflammatory drug |
ORIGIN |
Outcome Reduction with Initial Glargine Intervention |
PET |
positron emission tomography |
PREDIMED |
Prevención con Dieta Mediterránea trial |
PreDIVA |
Prevention of Dementia by Intensive Vascular Care |
PROGRESS |
Perindopril Protection against Recurrent Stroke Study |
RCT |
randomized controlled trial |
REGARDS |
Reasons for Geographical and Racial Differences in Stroke study |
RR |
relative risk |
SBP |
systolic blood pressure |
SCOPE |
Study on Cognition and Prognosis in the Elderly |
SPRINT |
Systolic Blood Pressure Intervention Trial |
SSRI |
selective serotonin reuptake inhibitor |
USPSTF |
U.S. Preventive Services Task Force |
WHIMS |
Women’s Health Initiative Memory Study |
WHISCA |
Women’s Health Initiative Study of Cognitive Aging |
WHO |
World Health Organization |