Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Corresponding Author
Reisa A. Sperling
Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Corresponding author. Tel.: + 1-617-732-8085; Fax: +1-617-264-5212.
E-mail address: [email protected]
Search for more papers by this authorPaul S. Aisen
Department of Neurosciences, University of California San Diego, San Diego, CA, USA
Search for more papers by this authorLaurel A. Beckett
Division of Biostatistics, School of Medicine, University of California, Davis, CA, USA
Search for more papers by this authorDavid A. Bennett
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
Search for more papers by this authorSuzanne Craft
Department of Psychiatry and Behavioral Sciences, Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound; University of Washington School of Medicine, Seattle, WA, USA
Search for more papers by this authorAnne M. Fagan
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Search for more papers by this authorTakeshi Iwatsubo
Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Search for more papers by this authorClifford R. Jack Jr.
Department of Radiology, Mayo Clinic Minnesota, Rochester, MN, USA
Search for more papers by this authorJeffrey Kaye
Departments of Neurology and Biomedical Engineering, Layton Aging & Alzheimer's Disease Center, Oregon Center for Aging & Technology, Oregon Health & Science University and Portland Veteran's Affairs Medical Center, Portland, OR, USA
Search for more papers by this authorThomas J. Montine
Department of Pathology, University of Washington, Seattle, WA, USA
Search for more papers by this authorDenise C. Park
Center for Vital Longevity, University of Texas at Dallas, Dallas, TX, USA
Search for more papers by this authorChristopher C. Rowe
Austin Health, University of Melbourne, Melbourne, Australia
Search for more papers by this authorYaakov Stern
Cognitive Neuroscience Division, Taub Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA
Search for more papers by this authorKristine Yaffe
Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California San Francisco, San Francisco VA Medical Center, San Francisco, CA, USA
Search for more papers by this authorMarcelle Morrison-Bogorad
Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorMolly V. Wagster
Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorCreighton H. Phelps
Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorCorresponding Author
Reisa A. Sperling
Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Corresponding author. Tel.: + 1-617-732-8085; Fax: +1-617-264-5212.
E-mail address: [email protected]
Search for more papers by this authorPaul S. Aisen
Department of Neurosciences, University of California San Diego, San Diego, CA, USA
Search for more papers by this authorLaurel A. Beckett
Division of Biostatistics, School of Medicine, University of California, Davis, CA, USA
Search for more papers by this authorDavid A. Bennett
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
Search for more papers by this authorSuzanne Craft
Department of Psychiatry and Behavioral Sciences, Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound; University of Washington School of Medicine, Seattle, WA, USA
Search for more papers by this authorAnne M. Fagan
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Search for more papers by this authorTakeshi Iwatsubo
Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Search for more papers by this authorClifford R. Jack Jr.
Department of Radiology, Mayo Clinic Minnesota, Rochester, MN, USA
Search for more papers by this authorJeffrey Kaye
Departments of Neurology and Biomedical Engineering, Layton Aging & Alzheimer's Disease Center, Oregon Center for Aging & Technology, Oregon Health & Science University and Portland Veteran's Affairs Medical Center, Portland, OR, USA
Search for more papers by this authorThomas J. Montine
Department of Pathology, University of Washington, Seattle, WA, USA
Search for more papers by this authorDenise C. Park
Center for Vital Longevity, University of Texas at Dallas, Dallas, TX, USA
Search for more papers by this authorChristopher C. Rowe
Austin Health, University of Melbourne, Melbourne, Australia
Search for more papers by this authorYaakov Stern
Cognitive Neuroscience Division, Taub Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA
Search for more papers by this authorKristine Yaffe
Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California San Francisco, San Francisco VA Medical Center, San Francisco, CA, USA
Search for more papers by this authorMarcelle Morrison-Bogorad
Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorMolly V. Wagster
Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorCreighton H. Phelps
Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorAbstract
The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
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