@article{3da12ddf07464b419839a4e658061ed9,
title = "AD risk score for the early phases of disease based on unsupervised machine learning",
abstract = "Introduction: Identifying cognitively normal individuals at high risk for progression to symptomatic Alzheimer's disease (AD) is critical for early intervention. Methods: An AD risk score was derived using unsupervised machine learning. The score was developed using data from 226 cognitively normal individuals and included cerebrospinal fluid, magnetic resonance imaging, and cognitive measures, and validated in an independent cohort. Results: Higher baseline AD progression risk scores (hazard ratio = 2.70, P < 0.001) were associated with greater risks of progression to clinical symptoms of mild cognitive impairment (MCI). Baseline scores had an area under the curve of 0.83 (95% confidence interval: 0.75 to 0.91) for identifying subjects who progressed to MCI/dementia within 5 years. The validation procedure, using data from the Alzheimer's Disease Neuroimaging Initiative, demonstrated accuracy of prediction across the AD spectrum. Discussion: The derived risk score provides high predictive accuracy for identifying which individuals with normal cognition are likely to show clinical decline due to AD within 5 years.",
keywords = "Alzheimer's disease, cognitive testing, latent variable, machine learning, multidomain biomarkers, progression, risk score, unsupervised learning",
author = "Zheyu Wang and Zhuojun Tang and Yuxin Zhu and Corinne Pettigrew and Anja Soldan and Alden Gross and Marilyn Albert",
note = "Funding Information: We are grateful for the support of the entire BIOCARD study team at Johns Hopkins University, the ADNI study team, and to the dedicated participants who continue to participate in these studies. This study was funded by a pilot project grant from the Johns Hopkins Alzheimer's Disease Research Center (P50-AG00146). Dr. Gross was supported by NIA K01-AG050699. The BIOCARD study is supported by a grant from the National Institute on Aging: U19-AG033655. The BIOCARD Study consists of 7 Cores with the following members: (1) the Administrative Core (Marilyn Albert, Rostislav Brichko), (2) the Clinical Core (Marilyn Albert, Anja Soldan, Corinne Pettigrew, Rebecca Gottesman, Ned Sacktor, Scott Turner, Leonie Farrington, Maura Grega, Gay Rudow, Scott Rudow), (3) the Imaging Core (Michael Miller, Susumu Mori, Tilak Ratnanather, Anthony Kolasny, Kenichi Oishi, Laurent Younes), (4) the Biospecimen Core (Abhay Moghekar, Jacqueline Darrow, Richard O'Brien), (5) the Informatics Core (Roberta Scherer, David Shade, Ann Ervin, Jennifer Jones, Hamadou Coulibaly, April Patterson), the (6) Biostatistics Core (Mei-Cheng Wang, Daisy Zhu, Jiangxia Wang), and (7) the Neuropathology Core (Juan Troncoso, Olga Pletnikova, Gay Rudow, Karen Fisher). The ADNI 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.; Cogstate; 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 Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: We are grateful for the support of the entire BIOCARD study team at Johns Hopkins University, the ADNI study team, and to the dedicated participants who continue to participate in these studies. This study was funded by a pilot project grant from the Johns Hopkins Alzheimer's Disease Research Center (P50‐AG00146). Dr. Gross was supported by NIA K01‐AG050699. The BIOCARD study is supported by a grant from the National Institute on Aging: U19‐AG033655. Funding Information: The ADNI 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.; Cogstate; 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 Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2020 the Alzheimer's Association",
year = "2020",
month = nov,
doi = "10.1002/alz.12140",
language = "English (US)",
volume = "16",
pages = "1524--1533",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "11",
}