Preventing and Treating Dementia: Research Priorities to Accelerate Progress (2025)
Chapter: Front Matter
Consensus Study Report
NATIONAL ACADEMIES PRESS 500 Fifth Street, NW, Washington, DC 20001
This activity was supported by a contract between the National Academy of Sciences and the National Institutes of Health, Department of Health and Human Services, and has been funded in whole or in part with federal funds under Contract No. HHSN263201800029I/75N98023F00003. 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: 978-0-309-73151-5
International Standard Book Number-10: 0-309-73151-8
Digital Object Identifier: https://doi.org/10.17226/28588
Library of Congress Control Number: 2025931436
This publication is available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2025 by the National Academy of Sciences. National Academies of Sciences, Engineering, and Medicine and National Academies Press and the graphical logos for each are all trademarks of the National Academy of Sciences. All rights reserved.
Printed in the United States of America.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2025. Preventing and treating dementia: Research priorities to accelerate progress. Washington, DC: The National Academies Press. https://doi.org/10.17226/28588.
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.
The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president.
The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.
The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.
Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.
Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.
Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.
Rapid Expert Consultations published by the National Academies of Sciences, Engineering, and Medicine are authored by subject-matter experts on narrowly focused topics that can be supported by a body of evidence. The discussions contained in rapid expert consultations are considered those of the authors and do not contain policy recommendations. Rapid expert consultations are reviewed by the institution before release.
For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.
COMMITTEE ON RESEARCH PRIORITIES FOR PREVENTING AND TREATING ALZHEIMER’S DISEASE AND RELATED DEMENTIAS1
TIA POWELL (Chair), Professor of Epidemiology and Psychiatry, Division of Bioethics, Albert Einstein College of Medicine, Montefiore Medical Center
RHODA AU, Professor of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine
RITA BALICE-GORDON, CEO, Muna Therapeutics
DANIEL BARRON, Director, Pain Intervention & Digital Research, Brigham & Women’s Hospital and Spaulding Rehabilitation Hospital, Mass General Brigham
CHRISTIAN BEHL, Professor of Pathobiochemistry, Chair and Institute Director, University Medical Center of the Johannes Gutenberg University Mainz, Germany
JEFFREY L. DAGE, Senior Research Professor of Neurology, Indiana University School of Medicine
NILÜFER ERTEKIN-TANER, Chair, Department of Neuroscience and Professor of Neurology and Neuroscience, Mayo Clinic
MARIA GLYMOUR, Chair and Professor, Boston University School of Public Health
HECTOR M. GONZÁLEZ, Professor, University of California San Diego School of Medicine
SUSANNE M. JAEGGI, Professor of Psychology, Applied Psychology, and Music, Northeastern University
KENNETH LANGA, Cyrus Sturgis Professor of Medicine, University of Michigan
PAMELA LEIN, Professor of Neurotoxicology and Chair, University of California Davis School of Veterinary Medicine
DOREEN MONKS, Program Director (retired), Stroke Program, Saint Barnabas Medical Center
KRISSAN LUTZ MOSS, Clinical Education Manager (retired), Genentech; Advocate for National Council of Dementia Minds, Lewy Body Dementia Association, and Dementia Action Alliance
KENNETH S. RAMOS, Alkek Professor of Medical Genetics, Executive Director, Institute of Biosciences and Technology and Assistant Vice Chancellor, Texas A&M University System
REISA A. SPERLING, Professor of Neurology, Harvard Medical School
___________________
1 See Appendix C, Disclosure of Unavoidable Conflicts of Interest.
CHI UDEH-MOMOH, Assistant Professor of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine
LI-SAN WANG, Peter C. Nowell, M.D. Professor, University of Pennsylvania Perelman School of Medicine
JULIE ZISSIMOPOULOS, Professor, University of Southern California
Study Staff
OLIVIA C. YOST, Study Director
AUTUMN DOWNEY, Senior Program Officer
MOLLY CHECKSFIELD DORRIES, Senior Program Officer
LYDIA TEFERRA, Research Associate
ASHLEY BOLOGNA, Research Assistant
CLARE STROUD, Senior Director, Board on Health Sciences Policy
DANIEL WEISS, Director, Board on Behavioral, Cognitive, and Sensory Sciences
National Academy of Medicine International Health Policy Fellow
HEI MAN CHOW, Assistant Professor, School of Life Sciences, The Chinese University of Hong Kong
Consultants
PICO PORTAL, INC.
MICHELLE MIELKE, Wake Forest University
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:
ADAM L. BOXER, University of California, San Francisco
ROBERTA DIAZ BRINTON, University of Arizona
FIONA E. DUCOTTERD, University College London
HOWARD FILLIT, Alzheimer’s Drug Discovery Foundation
CARL V. HILL, Alzheimer’s Association
TIMOTHY J. HOHMAN, Vanderbilt University Medical Center
THOMAS K. KARIKARI, University of Pittsburgh
AMY J. H. KIND, University of Wisconsin
STORY LANDIS, National Institute of Neurological Disorders and Stroke (NINDS), retired
JESSICA LANGBAUM, Banner Alzheimer’s Institute
ALLAN L. LEVEY, Emory University
KAREN MARDER, Columbia University Irving Medical Center
IOANNIS PASCHALIDIS, Boston University
LON S. SCHNEIDER, University of Southern California
RAJ C. SHAH, Rush University Medical Center
KRISTINE YAFFE, University of California, San Francisco
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 EILEEN M. CRIMMINS, University of Southern California and ALAN M. JETTE, Boston University. 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.
Acknowledgments
The committee would like to acknowledge and thank the study sponsor—the National Institutes of Health, and particularly the National Institute on Aging and the National Institute of Neurological Disorders and Stroke—for their leadership in the development of this project. The committee also wishes to thank the many other individuals who gave presentations and participated in discussions with the committee.
Additionally, the committee would like to express its gratitude to the National Academies staff who worked on the study: Olivia Yost, Autumn Downey, Molly Dorries, Lydia Teferra, and Ashley Bologna, as well as National Academy of Medicine International Fellow, Hei Man Chow. The committee is also grateful for the contributions of Mark Goodin, editor; the team at PICO Portal, Inc. for their support with the scoping review; and Rebecca Morgan of the National Academies Research Center for her assistance with literature search strategy.
This page intentionally left blank.
Healthy Aging, Resilience, and Brain Health Across the Life Course
The Exposome and Brain Health Across the Life Course
Understanding the Biological Basis of AD/ADRD
4 DEVELOPMENT AND EVALUATION OF INTERVENTIONS FOR THE PREVENTION AND TREATMENT OF AD/ADRD
A Framework for Considering Prevention and Treatment Strategies
Current State of Evidence on Interventions for Preventing and Treating AD/ADRD
Opportunities to Improve Clinical Trials for AD/ADRD
Advancing a Precision Medicine Approach to AD/ADRD Prevention and Treatment
Advancing Key Scientific Priorities Related to Preventing and Treating AD/ADRD
B Biographical Sketches of Committee Members and Staff
Boxes, Figures, and Tables
BOXES
S-1 Descriptions of Alzheimer’s Disease and Related Dementias
1-2 Descriptions of Alzheimer’s Disease and Related Dementias
1-3 Sex and Gender Differences in Alzheimer’s Disease and Related Dementias (AD/ADRD)
1-4 Strategies for Goals 1 and 6 of the National Plan to Address Alzheimer’s Disease
2-1 Biological Definitions for Alzheimer’s Disease and Related Dementias (AD/ADRD)
2-2 Addressing the Stigma Associated with AD/ADRD
2-3 Consortium for Detecting Cognitive Impairment Including Dementia
2-4 In-Home Monitoring: Advances from the Collaborative Aging Research Using Technology Initiative
2-5 Diagnostic Potential of Digital Data Combined with Artificial Intelligence
2-7 Progress in the Discovery of Fluid Biomarkers for Related Dementias
2-9 The Health and Aging Brain Study: Health Disparities
2-11 Harmonized Cognitive Assessment Protocol
2-12 Examples of the Integration of New Tools into Clinical Diagnostic Criteria
3-1 Alzheimer’s Disease Sequencing Project
3-2 Epigenetic Influences and Gene–Environment Interactions
3-4 The Accelerating Medicines Partnership®
3-5 Target Enablement to Accelerate Therapy Development for Alzheimer’s Disease (TREAT-AD)
4-1 Accelerated Decision Making in a Platform Trial: Lessons from I-SPY and Breast Cancer
4-2 Precision Medicine Advances in Breast, Lung, and Other Cancers
A-1 Overview of Quality Assessment Process
FIGURES
S-1 Committee recommendations for advancing the prevention and treatment of AD/ADRD
1-2 Percentage changes in selected causes of death (all ages) between 2000 and 2019
2-1 Data collection opportunities and approaches throughout the life course
2-3 Biomarkers across the clinical continuum
3-1 Twelve hallmarks of aging reflecting the erosion of hallmarks of health
3-2 Facets of the exposome that influence brain health
3-4 The neurovascular unit showing pericyte connections
4-1 Umbrella and basket trial designs
4-2 Schematic of a platform trial design
4-3 Evolution from one-size-fits-all to a personalized precision medicine model
5-1 Committee recommendations for advancing the prevention and treatment of AD/ADRD
TABLES
Preface
Our understanding of dementia has changed in important ways and so should our research. We have learned so much in the last decade. We have learned that the majority of those who suffer from clinical dementia show a mix of different pathologies, rather than a single type. Though many living with clinical dementia show the amyloid plaques and tau tangles of Alzheimer’s disease (AD), the majority of those people also show the hallmark pathologies of vascular, Lewy body, or other types of dementia. Interestingly, many older people without cognitive impairment also show plaques and tangles. So far, we do not know how these different pathologies interact to cause symptoms. We do not know the chain of causation for those different pathologies, and we do not know the best points in that chain for interventions that will prevent, delay, or even cure dementia. We have the start of therapeutics for Alzheimer’s dementia, yet those with the APOE4 gene variant, a large group with increased risk for AD, are at heightened risk for the side effects of current medications. Worse yet, we have no FDA-approved drugs for related dementias that are not Alzheimer’s type beyond those for managing symptoms.
We have learned that the percentage of older people living with clinical dementia is decreasing in the United States, which is tremendous news. This improvement may result from changes in factors such as fitness, education, smoking cessation, and blood pressure control. We have not learned, however, how to ensure that those benefits reach populations who are disproportionately affected by dementia. For despite all we’ve learned, the risk of clinical dementia remains far greater among vulnerable populations. We need to continue working to address these health inequalities. We know that
social isolation and loss of hearing and vision increase the risk of dementia, but we have yet to provide sufficient access to effective, widely available interventions to protect against these losses. We have learned that the process of diagnosing specific types of dementia can be time-consuming and too often inaccurate. We have not yet developed and validated sufficiently accurate, scalable, and affordable methods for use in clinical settings for assessing cognitive health and identifying how and when it starts to deteriorate. Without that knowledge, it will be difficult to develop and offer treatments tailored to individual needs.
This report’s mandate is to assess the current state of research on Alzheimer’s disease and related dementias (AD/ADRD), for both pharmacological and nonpharmacological interventions; to identify barriers to preventing and treating AD/ADRD; and to review the most promising areas of research—all with the goal of identifying appropriate research priorities for National Institutes of Health (NIH) funding. NIH and the many researchers it funds have produced an enormous increase, especially in the last decade, in the available knowledge regarding AD/ADRD. This report is the result of more than a year’s effort by many people, ranging from dedicated National Academies of Sciences, Engineering, and Medicine staff, engaged and thoughtful committee members, experts presenting at our public meetings, and the author of a commissioned paper. We hope this report will build upon the good work already accomplished and guide NIH research priorities toward further explorations that will help prevent and treat AD/ADRD. For though the percentage of older people living with clinical dementia is decreasing, the overall numbers of those living with dementia in our aging population continue to increase. We are in dire need, today and in the future, for greater knowledge and more effective prevention and treatment for AD/ADRD.
Tia Powell, Chair
Committee on Research Priorities for Preventing and Treating Alzheimer’s Disease and Related Dementias
