@article{c93b85b575cf479983a685cc09a26bee,
title = "The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design",
abstract = "Introduction We investigated the influence of different inclusion criteria for preclinical and prodromal Alzheimer's disease (AD) on changes in biomarkers and cognitive markers and on trial sample size estimates. Methods We selected 522 cognitively normal subjects and 872 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study. Compared inclusion criteria were (1) preclinical or prodromal AD (amyloid marker abnormal); (2) preclinical or prodromal AD stage-1 (amyloid marker abnormal, injury marker normal); and (3) preclinical or prodromal AD stage-2 (amyloid and injury markers abnormal). Outcome measures were amyloid, neuronal injury, and cognitive markers. Results In both subjects with preclinical and prodromal AD stage-2, inclusion criteria resulted in the largest observed decline in brain volumetric measures on magnetic resonance imaging and cognitive markers. Discussion Inclusion criteria influence the observed rate of worsening in outcome measures. This has implications for trial design.",
keywords = "Alzheimer's disease, Biomarkers, Clinical trial, Cognitive markers, Longitudinal, Preclinical, Prodromal, Sample size estimates",
author = "Daniela Bertens and Tijms, \{Betty M.\} and Lisa Vermunt and Prins, \{Niels D.\} and Philip Scheltens and Visser, \{Pieter Jelle\} and \{Alzheimer's Disease Neuroimaging Initiative (ADNI)\}",
note = "Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc; Eisai Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; Euroimmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research \& Development, LLC; Johnson \& Johnson Pharmaceutical Research \& Development LLC; Lumosity; Lundbeck; Merck \& Co., Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 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. Funding Information: Dr N.D.P. serves on the advisory board of Boehringer Ingelheim, Forum, and Probiodrug and has provided consultancy services for Sanofi and Takeda. He has been a speaker at symposia organized by Janssen and Novartis. N.D.P. receives research support from Alzheimer Nederland (project number WE.03-2012-02). N.D.P. is CEO and co-owner of the Alzheimer Research Center, Amsterdam, The Netherlands. Dr P.S. has received grant support (for the institution) from GE Healthcare, Danone Research, Piramal, and MERCK. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, GE Healthcare, Novartis, Forum, Sanofi, Nutricia, Probiodrug, and EIP Pharma. Dr P.J.V. serves as an advisory board member of Eli Lilly and is consultant for Janssen Pharmaceutical. He receives/received research grants from Bristol-Myers Squibb and GE Healthcare, European Commission 6th and 7th Framework programme, the Innovative Medicines Initiative (IMI), European Union Joint Programme–Neurodegenerative Disease Research (JPND), and Zon-Mw. Publisher Copyright: {\textcopyright} 2017",
year = "2017",
month = nov,
day = "1",
doi = "10.1016/j.trci.2017.08.005",
language = "English",
volume = "3",
pages = "513--523",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
publisher = "Elsevier Inc.",
number = "4",
}