@article{3a21a7659ff040ab841e8e32ae7c7e04,
title = "A computational neurodegenerative disease progression score: Method and results with the Alzheimer's disease neuroimaging initiative cohort",
abstract = "While neurodegenerative diseases are characterized by steady degeneration over relatively long timelines, it is widely believed that the early stages are the most promising for therapeutic intervention, before irreversible neuronal loss occurs. Developing a therapeutic response requires a precise measure of disease progression. However, since the early stages are for the most part asymptomatic, obtaining accurate measures of disease progression is difficult. Longitudinal databases of hundreds of subjects observed during several years with tens of validated biomarkers are becoming available, allowing the use of computational methods. We propose a widely applicable statistical methodology for creating a disease progression score (DPS), using multiple biomarkers, for subjects with a neurodegenerative disease. The proposed methodology was evaluated for Alzheimer's disease (AD) using the publicly available AD Neuroimaging Initiative (ADNI) database, yielding an Alzheimer's DPS or ADPS score for each subject and each time-point in the database. In addition, a common description of biomarker changes was produced allowing for an ordering of the biomarkers. The Rey Auditory Verbal Learning Test delayed recall was found to be the earliest biomarker to become abnormal. The group of biomarkers comprising the volume of the hippocampus and the protein concentration amyloid beta and Tau were next in the timeline, and these were followed by three cognitive biomarkers. The proposed methodology thus has potential to stage individuals according to their state of disease progression relative to a population and to deduce common behaviors of biomarkers in the disease itself.",
keywords = "Alzheimer's disease, Biomarkers, Disease progression score, Neurodegenerative diseases",
author = "Jedynak, {Bruno M.} and Andrew Lang and Bo Liu and Elyse Katz and Yanwei Zhang and Wyman, {Bradley T.} and David Raunig and Jedynak, {C. Pierre} and Brian Caffo and Prince, {Jerry L.}",
note = "Funding Information: Personnel costs for this research were partially supported by a grant from Pfizer Inc . Other support came from grants numbered P41EB015909 and R01EB012547 from the National Institute of Biomedical Imaging and Bioengineering as well as from an Ossoff Scholar Award . Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health grant U01 AG024904 ). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. 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 California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 . The first author would also like to thank Patrick Slama for his insightful remarks. Appendix A ",
year = "2012",
month = nov,
day = "15",
doi = "10.1016/j.neuroimage.2012.07.059",
language = "English (US)",
volume = "63",
pages = "1478--1486",
journal = "NeuroImage",
issn = "1053-8119",
publisher = "Academic Press Inc.",
number = "3",
}