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Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework

Ning, Kaida and Chen, Bo and Sun, Fengzhu and Hobel, Zachary and Zhao, Lu and Matloff, Will and Toga, Arthur W. (2018) Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework. Neurobiology of Aging, 68 . pp. 151-158. ISSN 0197-4580. PMCID PMC5993633. doi:10.1016/j.neurobiolaging.2018.04.009.

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A long-standing question is how to best use brain morphometric and genetic data to distinguish Alzheimer's disease (AD) patients from cognitively normal (CN) subjects and to predict those who will progress from mild cognitive impairment (MCI) to AD. Here, we use a neural network (NN) framework on both magnetic resonance imaging-derived quantitative structural brain measures and genetic data to address this question. We tested the effectiveness of NN models in classifying and predicting AD. We further performed a novel analysis of the NN model to gain insight into the most predictive imaging and genetics features and to identify possible interactions between features that affect AD risk. Data were obtained from the AD Neuroimaging Initiative cohort and included baseline structural MRI data and single nucleotide polymorphism (SNP) data for 138 AD patients, 225 CN subjects, and 358 MCI patients. We found that NN models with both brain and SNP features as predictors perform significantly better than models with either alone in classifying AD and CN subjects, with an area under the receiver operating characteristic curve (AUC) of 0.992, and in predicting the progression from MCI to AD (AUC=0.835). The most important predictors in the NN model were the left middle temporal gyrus volume, the left hippocampus volume, the right entorhinal cortex volume, and the APOE (a gene that encodes apolipoprotein E) ɛ4 risk allele. Furthermore, we identified interactions between the right parahippocampal gyrus and the right lateral occipital gyrus, the right banks of the superior temporal sulcus and the left posterior cingulate, and SNP rs10838725 and the left lateral occipital gyrus. Our work shows the ability of NN models to not only classify and predict AD occurrence but also to identify important AD risk factors and interactions among them.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Chen, Bo0000-0001-5566-7361
Sun, Fengzhu0000-0002-8552-043X
Hobel, Zachary0000-0002-8229-027X
Matloff, Will0000-0002-1584-9416
Toga, Arthur W.0000-0001-7902-3755
Additional Information:© 2018 Elsevier Inc. Received 17 July 2017, Revised 16 April 2018, Accepted 16 April 2018, Available online 24 April 2018. This work was supported by grants P41EB015922, U54EB020406 and R01MH094343 of the National Institutes of Health. 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 ( 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. The authors have no conflicts of interest to disclose.
Funding AgencyGrant Number
NIHU01 AG024904
Department of DefenseW81XWH-12-2-0012
Alzheimer's AssociationUNSPECIFIED
Alzheimer's Drug Discovery FoundationUNSPECIFIED
Araclon BiotechUNSPECIFIED
Bristol-Myers SquibbUNSPECIFIED
Elan Pharmaceuticals, Inc.UNSPECIFIED
Eli Lilly and CompanyUNSPECIFIED
F. Hoffmann-La Roche Ltd.UNSPECIFIED
Genentech, Inc.UNSPECIFIED
Janssen Alzheimer Immunotherapy Research & Development, LLCUNSPECIFIED
Johnson & Johnson Pharmaceutical Research & Development LLCUNSPECIFIED
Meso Scale Diagnostics, LLCUNSPECIFIED
Neurotrack TechnologiesUNSPECIFIED
Novartis PharmaceuticalsUNSPECIFIED
Piramal ImagingUNSPECIFIED
Takeda Pharmaceutical CompanyUNSPECIFIED
Transition TherapeuticsUNSPECIFIED
Canadian Institutes of Health Research (CIHR)UNSPECIFIED
Foundation for the National Institutes of HealthUNSPECIFIED
Northern California Institute for Research and EducationUNSPECIFIED
Subject Keywords:Alzheimer's disease; Mild cognitive impairment; Brain imaging; Genetics; Neural network; Understanding neural network
PubMed Central ID:PMC5993633
Record Number:CaltechAUTHORS:20180726-083142890
Persistent URL:
Official Citation:Kaida Ning, Bo Chen, Fengzhu Sun, Zachary Hobel, Lu Zhao, Will Matloff, Arthur W. Toga, Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework, Neurobiology of Aging, Volume 68, 2018, Pages 151-158, ISSN 0197-4580,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:88295
Deposited By: Tony Diaz
Deposited On:26 Jul 2018 15:43
Last Modified:18 Mar 2022 17:54

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