Study concept and design: Ossenkoppele, Jansen, Visser.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Ossenkoppele, Jansen, Rabinovici, Visser.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Ossenkoppele, Jansen, Knol, Visser.
Obtained funding: Rabinovici, van der Flier, Lammertsma, Jagust, Miller, Villemagne, Rowe, Lee, Na, Seo, Sarazin, Roe, Sabri, Barthel, Koglin, Hodges, Leyton, Vandenberghe, van Laere, Drzezga, Forster, Grimmer, Sánchez-Juan, Carril, Mok, Camus, Klunk, Cohen, Meyer, Hellwig, Newberg, Frederiksen, Fleisher, Mintun, Wolk, Nordberg, Rinne, Chételat, Lleo, Blesa, Fortea, Madsen, Rodrigue, Brooks, van Berckel, Scheltens, Visser.
Administrative, technical, or material support: All authors.
Study supervision: Visser.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.Dr Rabinovici reports receiving grant funding from Avid Radiopharmaceuticals and personal fees GE Healthcare and Piramal. Dr van der Flier reports receiving grant funding from Boehringer Ingelheim, Piramal, and Roche Europe BV. Dr Scheltens reports receiving grant funding from GE Healthcare, Piramal, and Merck. Dr Zwan reports grant funding from GE Healthcare. Dr Visser reports receiving grants from European Union/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Joint Undertaking, European Union Joint Programme—Neurodegenerative Disease Research, Bristol-Myers Squibb, and ZonMw; and other support from Roche Diagnostics and GE Healthcare. Dr Lammertsma reports receiving grant funding from the International Stichting Alzheimer Onderzoek, Center for Translational Molecular Medicine, Philips, and Avid and personal fees from Philips. Dr Barkhof reports receiving consulting fees for Bayer Schering Pharma, sanofi-aventis, Biogen, TEVA, Merck Serono, Novartis, Roche, Synthon BV, Jansen Research, Genzyme, grants from the Dutch Multiple Sclerosis Society, and speaker fees from Serono Symposia and Medscape. Dr Jagust reports receiving personal fees from Banner Alzheimer Institute/Genentech, Synarc/Bioclinica, and Novartis. Dr Miller reports receiving grant support from the National Institutes of Health/National Institute on Aging (NIH/NIA) and the Centers for Medicare & Medicaid Services (CMS) as grants for the Memory and Aging Center; serving as medical director for the John Douglas French Foundation, scientific director for the Tau Consortium, director/medical advisory board of the Larry L. Hillblom Foundation, and the scientific advisory board member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK). Dr Landau reports receiving grant funding from NIH and personal fees from Biogen Idec, Genentech, and Synarc. Dr Rowe reports receiving research grants in the last 2 years from Piramal, GE Healthcare, Avid/Lilly, Navidia, and AstraZeneca; giving talks at educational meetings arranged by Piramal and GE Healthcare; and receiving personal fees from Roche. Dr Sarazin reports receiving personal fees from Novartis and Allianz. Dr Sabri reports receiving grant funding from Pirimal Imaging, Bayer HealthCare, and personal fees from Bayer HealthCare and GE Healthcare. Dr Barthel reports receiving personal fees from Piramal Imaging and Siemens Healthcare. Dr Koglin reports receiving personal fees from Piramal Imaging, which is marketing Neuraceq ([F18]florbetaben) as an amyloid-β PET imaging agent. Dr Vandenberghe reports receiving support from GEHC, Merck, Forum and Roche; grant funding from Research Foundation—Flanders (FWO) and KU Leuven; and nonfinancial support from GEHC. Dr Van Laere reports receiving grants from Merck, Janssens Pharmaceuticals, and GE Healthcare. Dr Drzezga reports receiving speaker honoraria and consulting fees from GE Healthcare, AVID/Lilly, and Piramal and grant funding from the German Research Foundation. Dr Forster reports receiving personal fees from Piramal, Bayer, and GE Healthcare. Dr Grimmer reports receiving personal fees from Eli Lilly. Dr Camus reports receiving grants from French Ministry of Health. Dr Klunk reports being co-inventor of the amyloid imaging tracer PiB, which is owned by the University of Pittsburgh and licensed to GE Healthcare; and receiving payments from the University of Pittsburgh from that license. Dr Meyer reports grants from GE Healthcare. Dr Hellwig reports grant funding from GE Healthcare and the University of Freiburg. Dr Fleisher reports receiving support from Eli Lilly, Merck, and Pfizer; grant support from National Institute of Aging, Avid Radiopharmaceuticals, and Eli Lilly; personal fees from Grifols, Avid Radiopharmaceuticals, and Siemens; and being a full-time employee of the Banner Alzheimer's Institute and a full-time employee of Eli Lilly at the time of submission; maintaining a voluntary faculty appointment at the University of California, San Diego. Dr Mintun reports being an employee of Avid Radiopharmaceuticals. Dr Wolk reports consulting for GE Healthcare and being a site private investigator for a clinical trial supported by AVID/Lilly. Dr Rinne reports receiving grant funding from Sigrid Juselius Foundation and Turku University Hospital. Dr Lleo reports grant funding from Instituto de Salud Carlos III and the CIBERNED program. Dr Fortea reports receiving grant funding from Instituto de Salud Carlos III. Dr Madsen reports receiving grant funding from the Lundbeck Foundation, the Dagmar Marshalls Fond, and the Danish Medical Council. The authors received salary as employees of their respective organizations. Dr Brooks reports receiving consulting fees from GE Healthcare. No other disclosures are reported.
Funding/Support: The National Alzheimer's Coordinating Center (NACC) database is funded by grant U01 AG016976 from the National Institute on Aging. The Alzheimer’s Disease Neuroimaging Initiative (ADNI; National Institutes of Health, grant U01 AG024904) is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences; AstraZeneca; Bayer HealthCare; BioClinica; Biogen Idec; Bristol-Myers Squibb; Eisai; Elan Pharmaceuticals; Eli Lilly; F. Hoffmann-La Roche and its affiliated company Genentech; GE Healthcare; Innogenetics, NV; IXICO; Janssen Alzheimer Immunotherapy Research and Development; Johnson & Johnson Pharmaceutical Research and Development; Medpace; Merck and Company; Meso Scale Diagnostics; Novartis Pharmaceuticals; Pfizer; Servier; Synarc; and Takeda Pharmaceutical. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study was coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of California, Los Angeles. Funding for the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study was provided in part by the study partners (Australian Commonwealth Scientific Industrial and Research Organization [CSIRO], Edith Cowan University [ECU], Mental Health Research Institute [MHRI], Alzheimer’s Australia [AA], National Ageing Research Institute [NARI], Austin Health, CogState, Hollywood Private Hospital, Sir Charles Gardner Hospital). The study also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as ongoing funding from the Science and Industry Endowment Fund (SIEF). The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. The florbetaben phase 2 study, from which data were derived for this multicenter evaluation, was sponsored by Bayer Healthcare/Piramal Imaging (Berlin, Germany). The assembling of the TU Munich data set was supported in part by the German research foundation (Deutsche Forschungsgemeinschaft; HE 4560/1-2, DR 445/3-1 and DR 445/4-1 to Dr Drzezga), and by a KKF-grant for clinical research of the Technische Universität München (to Drs Drzezga and Grimmer). The amyloid PET studies of The Chinese University of Hong Kong are supported by Health and Health Services Research Fund (06070231) and seeding money from Lui Che Woo Institute of Innovative Medicine. Funding for this study was provided by the National Institute on Aging (P50 AG005681, P01 AD 003991, and P01 AD 026276); Fred Simmons and Olga Mohan, and the Joanne Knight Alzheimer’s Research Initiative of the Washington Knight Alzheimer’s Disease Research Center. The study in Tours was financially supported by the French Ministry of Health (grant PHRC-N 2008 1004) and the EC-FP6-project (DiMI, LSHB-CT-2005-512146). Data from the University of Pennsylvania was supported by the Pennsylvanian Department of Health (4100037703). Data from Washington University in St Louis was supported by grants NIH NCRR UL1RR024992, NINDS NS075321, the American Parkinson Disease Association (APDA) Advanced Research Center for Parkinson Disease at Washington University in St. Louis, and the Greater St Louis Chapter of the APDA. This research was performed within the framework of The Center for Translational Molecular Medicine (CTMM; http://www.ctmm.nl), project LeARN (grant 02N-101). The Caen study was funded by Agence Nationale de la Reserche, Programme Hospitalier de Reserche Clinique, Region Basse Normandie, and Institut National de la Sante et de la Reserche Medicale (INSERM).
Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors’ respective organizations were given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.
Disclaimer: Any views expressed in this publication represent the personal opinions of the authors, and not those of their respective employer.
Additional Contributions: Multicenter studies involved in this study: Alzheimer’s Disease Neuroimaging Initiative (ADNI); Australian Imaging, Biomarkers & Lifestyle (AIBL) study; Avid Pharmaceuticals multicenter study for the AV45-A17 Study Group; Florbetaben (FBB) Phase 2 multicenter study; Leiden Alzheimer-Research Nederland (LeARN) project; Multicenter study by UK Hospitals and University Hospital of Turku. Part of the data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this article. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Additional information is available in the Supplement.
Correction: This article was corrected for typographical errors on June 11, 2015.