@article{401a25ccc7fc45f49986401f9c371d98,
title = "Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease",
abstract = "Background It is unknown which commonly used Alzheimer disease (AD) biomarker values - baseline or progression - best predict longitudinal cognitive decline. Methods 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. Results About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. Conclusions For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers.",
keywords = "ADNI, ADNI-exe, ADNI-mem, Biomarker, Biomarker progressions, Cognitive declines, FDG-PET, MCI, MRI volume",
author = "Dodge, {Hiroko H.} and Jian Zhu and Danielle Harvey and Naomi Saito and Silbert, {Lisa C.} and Kaye, {Jeffrey A.} and Koeppe, {Robert A.} and Albin, {Roger L.}",
note = "Funding Information: Data collection and sharing for this project were 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 Alzheimer's Association; Alzheimer's Drug Discovery Foundation; 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.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; 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 National Institutes of Health grant ( P30 AG010129 ). Additional funding includes National Institute on Aging ( P30 AG008017 , 1R01AG036772 , and R13 AG030995 ) and Michigan Alzheimer's Disease Center Pilot Grant. ",
year = "2014",
month = nov,
day = "1",
doi = "10.1016/j.jalz.2014.04.513",
language = "English (US)",
volume = "10",
pages = "690--703",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "6",
}