Advancing research diagnostic criteria for Alzheimer's disease: The IWG-2 criteria

Bruno Dubois, Howard H. Feldman, Claudia Jacova, Harald Hampel, José Luis Molinuevo, Kaj Blennow, Steven T. Dekosky, Serge Gauthier, Dennis Selkoe, Randall Bateman, Stefano Cappa, Sebastian Crutch, Sebastiaan Engelborghs, Giovanni B. Frisoni, Nick C. Fox, Douglas Galasko, Marie Odile Habert, Gregory A. Jicha, Agneta Nordberg, Florence PasquierGil Rabinovici, Philippe Robert, Christopher Rowe, Stephen Salloway, Marie Sarazin, Stéphane Epelbaum, Leonardo C. de Souza, Bruno Vellas, Pieter J. Visser, Lon Schneider, Yaakov Stern, Philip Scheltens, Jeffrey L. Cummings

Research output: Contribution to journalReview articlepeer-review

2373 Scopus citations


In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

Original languageEnglish
Pages (from-to)614-629
Number of pages16
JournalThe Lancet Neurology
Issue number6
StatePublished - Jun 2014

Bibliographical note

Funding Information:
BD has collaborated with Eli Lilly and Affiris, and has received grants for his institution from Roche and Pfizer. HHF was a full-time paid employee of Bristol-Myers Squibb from 2009 to 2011, on leave from the University of British Columbia (UBC), and received salary and stock holdings in this role. Since 2012, he has provided consulting through service agreements with Biogen Idec, Eli Lilly Pharmaceuticals, Kyowa Hakko Kirin, and GE Healthcare, for which UBC received payments. He received a speaker's honorarium from Danone, and has served on advisory boards with Fidelity Biosciences, for which he received travel and meeting expenses. HH has received honoraria, travel expenses, consulting fees, or research grants from Boehringer lngelheim, Bristol-Myers Squibb, Elan Corporation, Wyeth, Novartis, Eisai, Pfizer, Schwabe, Sanofi-Aventis, Roche Pharmaceuticals and Diagnostics, GE Healthcare, AstraZeneca, Avid, Eli Lilly and Company, Janssen-Cilag, Merz Pharmaceuticals, GlaxoSmithKline Biologicals, Jung Diagnostics, and Thermo Fisher Scientific Clinical Diagnostics BRAHM S GmbH. KB has served on advisory boards for lnnogenetics, Pfizer, and Roche. STDK has worked as a consultant for drug development for Pfizer, Merck, Lilly, Genzyme, AstraZeneca, and Helicon Therapeutics. He is also the principal investigator at the University of Virginia Memory Disorders Clinics for Elan, Novartis, Janssen, Pfizer, and Baxter. DS has been a consultant for Elan Corporation. RB is co-founder and part owner of C2N Diagnostics. He has received grants, consultancy fees, or speaker's fees from AstraZeneca, Merck, a pharma consortium (Biogen Idec, Elan Pharmaceuticals, Eli Lilly and Company, Hoffman-La Roche, Genentech, Janssen Alzheimer's Immunotherapy, Mithridion, Novartis Pharma AG, Pfizer Biotherapeutics R&D, Sanofi-Aventis, Eisai), Genentech, Roche, and Sanofi. SCa has received honoraria as a conference speaker for Novartis and Serono, and reimbursement for travel grants from Novartis and Nutricia. NCF has received research funding from Janssen, Elan Corporation, Lundbeck, Pfizer, Sanofi, and Wyeth; he has received no personal compensation for these activities. DG has received funding for research and clinical trials from Eli Lilly; he serves on Data and Safety Monitoring Boards for Pfizer, Elan Corporation, and Balance Pharmaceuticals. AN received honoraria for her participation on scientific advisory boards with Elan Corporation, Merck, GE Healthcare, Lundbeck AB, Pfizer, Avid Radiopharmaceuticals, (a wholly owned subsidiary of Eli Lilly), Johnson & Johnson, and Cytox; and as a speaker for Novartis, Bayer Health, Janssen-Cilag, Pfizer, Merz, and Envivo. Her department has received grants from GE Healthcare and Bayer Health. FP has received fees for participation on scientific advisory boards for Eli Lilly, Sanofi, Novartis, Janssen, Pfizer, and Nutricia. GR has received consulting fees from Eli Lilly and speaker's honoraria from GE Healthcare. He receives research support from Avid Radiopharmaceuticals. PR has received an honorarium from Lundbeck and Eisai, and has participated in expert meetings for Roche, Lilly, and Elan. CR has received research grants from Bayer/Piramal, GE Healthcare, Avid Radiopharmaceuticals, and AstraZeneca. SS has received honoraria from GE Healthcare, Avid Radiopharmaceuticals/Lilly, Bayer, Bristol-Myers Squibb, Athena, Pfizer, Merck, Roche, Baxter, and Janssen Alzheimer's Immunotherapy; and research grants to his institution from Avid, Janssen Alzheimer's Immunotherapy, Baxter, Bristol-Myers Squibb, Pfizer, Genetech, GE Healthcare, Roche, Merck, and Biogen. PJV has served as an advisory board member for Bristol-Myers Squibb. He receives, and has received, research grants from Bristol-Myers Squibb. LS has received grants and research support from Baxter, Genentech, Johnson & Johnson, Eli Lilly, Lundbeck, Novartis, Pfizer, and Tau Rx. He has served as a consultant for, and received consulting fees from, Abbvie, AC Immune, Allon, AstraZeneca, Baxter, Biogen Idec, Biotie, Bristol-Myers Squibb, Cerespir, Chiesi, Elan, Eli Lilly, EnVivo, GlaxoSmithKline, Johnson & Johnson, Lundbeck, MedAvante, Merck, Novartis, Piramal, Pfizer, Roche, Servier, Takeda, Tau Rx, Toyama, and Zinfandel. PS received a grant for his institution from GE Healthcare for an investigator-initiated study. All other authors declare no competing interests.

ASJC Scopus subject areas

  • Clinical Neurology


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