Volume 7, Issue 3 p. 280-292
Featured Article

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

Reisa A. Sperling

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]

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Paul S. Aisen

Paul S. Aisen

Department of Neurosciences, University of California San Diego, San Diego, CA, USA

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Laurel A. Beckett

Laurel A. Beckett

Division of Biostatistics, School of Medicine, University of California, Davis, CA, USA

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David A. Bennett

David A. Bennett

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA

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Suzanne Craft

Suzanne 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

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Anne M. Fagan

Anne M. Fagan

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

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Takeshi Iwatsubo

Takeshi Iwatsubo

Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

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Clifford R. Jack Jr.

Clifford R. Jack Jr.

Department of Radiology, Mayo Clinic Minnesota, Rochester, MN, USA

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Jeffrey Kaye

Jeffrey 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

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Thomas J. Montine

Thomas J. Montine

Department of Pathology, University of Washington, Seattle, WA, USA

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Denise C. Park

Denise C. Park

Center for Vital Longevity, University of Texas at Dallas, Dallas, TX, USA

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Eric M. Reiman

Eric M. Reiman

Banner Alzheimer's Institute, Phoenix, AZ, USA

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Christopher C. Rowe

Christopher C. Rowe

Austin Health, University of Melbourne, Melbourne, Australia

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Eric Siemers

Eric Siemers

Eli Lilly and Company, Indianapolis, IN, USA

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Yaakov Stern

Yaakov Stern

Cognitive Neuroscience Division, Taub Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA

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Kristine Yaffe

Kristine Yaffe

Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California San Francisco, San Francisco VA Medical Center, San Francisco, CA, USA

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Maria C. Carrillo

Maria C. Carrillo

Alzheimer's Association, Chicago, IL, USA

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Bill Thies

Bill Thies

Alzheimer's Association, Chicago, IL, USA

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Marcelle Morrison-Bogorad

Marcelle Morrison-Bogorad

Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA

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Molly V. Wagster

Molly V. Wagster

Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA

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Creighton H. Phelps

Creighton H. Phelps

Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA

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First published: 22 April 2011
Citations: 4,824

Abstract

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.