@article{35982813358f41c6807feb90b7ab64ab,
title = "Empowering imaging biomarkers of Alzheimer's disease",
abstract = "In a previous report, we proposed a method for combining multiple markers of atrophy caused by Alzheimer's disease into a single atrophy score that is more powerful than any one feature. We applied the method to expansion rates of the lateral ventricles, achieving the most powerful ventricular atrophy measure to date. Here, we expand our method's application to tensor-based morphometry measures. We also combine the volumetric tensor-based morphometry measures with previously computed ventricular surface measures into a combined atrophy score. We show that our atrophy scores are longitudinally unbiased with the intercept bias estimated at 2 orders of magnitude below the mean atrophy of control subjects at 1 year. Both approaches yield the most powerful biomarker of atrophy not only for ventricular measures but also for all published unbiased imaging measures to date. A 2-year trial using our measures requires only 31 (22, 43) Alzheimer's disease subjects or 56 (44, 64) subjects with mild cognitive impairment to detect 25% slowing in atrophy with 80% power and 95% confidence.",
keywords = "ADNI, Alzheimer's disease, Biomarker, Drug trial, Lateral ventricles, Linear discriminant analysis, Machine learning, Mild cognitive impairment, Shape analysis, Tensor-based morphometry",
author = "{Alzheimer's Disease Neuroimaging Initiative} and Gutman, {Boris A.} and Yalin Wang and Igor Yanovsky and Xue Hua and Toga, {Arthur W.} and Jack, {Clifford R.} and Weiner, {Michael W.} and Thompson, {Paul M.}",
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 ). 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 Fund ; Alzheimer's Association ; Alzheimer Drug Discovery Foundation ; Amorfix Life Sciences Ltd ; AstraZeneca ; Bayer Healthcare ; BioClinica, Inc ; Biogen ; Bristol-Myers Squibb Foundation ; Eisai ; Elan ; Eli Lilly and Company ; F. Hoffmann-La Roche Ltd and its affiliated company Genentech Foundation ; 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 ; Servier ; Synarc Inc ; and Takeda Pharmaceuticals North America . 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 Rev March 26, 2012 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 grants P30 AG010129 and K01 AG030514 . Algorithm development for this study was also funded by the National Institute on Aging , National Institute of Biomedical Imaging and Bioengineering , the U.S. National Library of Medicine , and the National Center for Research Resources ( AG016570 , EB01651 , LM05639 , and RR019771 to Paul M. Thompson). Author contributions were as follows: Boris A. Gutman wrote the manuscript. Boris A. Gutman, Xue Hua, Arthur W. Toga, and Paul M. Thompson performed image analyses. Boris A. Gutman, Yalin Wang, Igor Yanovsky, and Paul M. Thompson developed algorithms used in the analyses. Paul M. Thompson and Igor Yanovsky made substantial comments on the manuscript. Clifford R. Jack and Michael W. Weiner contributed substantially to the image and data acquisition, study design, quality control, calibration, and preprocessing, databasing, and image analysis. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jan,
day = "1",
doi = "10.1016/j.neurobiolaging.2014.05.038",
language = "English (US)",
volume = "36",
pages = "S69--S80",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "S1",
}