@article{32370a93a46941f9b938f69f6ec8082d,
title = "A Novel Ensemble-Based Machine Learning Algorithm to Predict the Conversion From Mild Cognitive Impairment to Alzheimer's Disease Using Socio-Demographic Characteristics, Clinical Information, and Neuropsychological Measures",
abstract = "Background: Despite the increasing availability in brain health related data, clinically translatable methods to predict the conversion from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) are still lacking. Although MCI typically precedes AD, only a fraction of 20-40% of MCI individuals will progress to dementia within 3 years following the initial diagnosis. As currently available and emerging therapies likely have the greatest impact when provided at the earliest disease stage, the prompt identification of subjects at high risk for conversion to AD is of great importance in the fight against this disease. In this work, we propose a highly predictive machine learning algorithm, based only on non-invasively and easily in-the-clinic collectable predictors, to identify MCI subjects at risk for conversion to AD.Methods: The algorithm was developed using the open dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI), employing a sample of 550 MCI subjects whose diagnostic follow-up is available for at least 3 years after the baseline assessment. A restricted set of information regarding sociodemographic and clinical characteristics, neuropsychological test scores was used as predictors and several different supervised machine learning algorithms were developed and ensembled in final algorithm. A site-independent stratified train/test split protocol was used to provide an estimate of the generalized performance of the algorithm.Results: The final algorithm demonstrated an AUROC of 0.88, sensitivity of 77.7%, and a specificity of 79.9% on excluded test data. The specificity of the algorithm was 40.2% for 100% sensitivity.Conclusions: The algorithm we developed achieved sound and high prognostic performance to predict AD conversion using easily clinically derived information that makes the algorithm easy to be translated into practice. This indicates beneficial application to improve recruitment in clinical trials and to more selectively prescribe new and newly emerging early interventions to high AD risk patients.",
keywords = "Alzheimer's disease, clinical prediction rule, machine learning, mild cognitive impairment, personalized medicine, precision medicine, neuropsychological tests, OLDER-ADULTS, DEMENTIA, INDIVIDUALS, MRI, MCI, STATE, RISK",
author = "Massimiliano Grassi and Nadine Rouleaux and Daniela Caldirola and David Loewenstein and Koen Schruers and Giampaolo Perna and Michel Dumontier and {Alzheimer's Disease Neuroimaging Initiative}",
note = "Funding Information: 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{\textquoteright}s Association; Alzheimer{\textquoteright}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{\textquoteright}s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. Funding Information: The authors would like to express their thanks to Lianne Ippel, Seun Onaopepo Adekunle, Alexander Malic, and Pedro Hernandez from the Institute of Data Science at Maastricht University for their valuable assistance, contributing their expertise to the experimental design of the analyses of this study. Data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). Funding Information: 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 NeuroImaging at the University of Southern California. Publisher Copyright: Copyright {\textcopyright} 2019 Grassi, Rouleaux, Caldirola, Loewenstein, Schruers, Perna, Dumontier and the Alzheimer's Disease Neuroimaging Initiative. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
month = jul,
day = "16",
doi = "10.3389/fneur.2019.00756",
language = "English",
volume = "10",
journal = "Frontiers in Neurology",
issn = "1664-2295",
publisher = "Frontiers Media S.A.",
}