Predicting Alzheimer’s disease progression using multi-modal deep learning approach

Garam Lee(Ajou University), Kwangsik Nho(Indiana University School of Medicine), Byungkon Kang(Ajou University), Kyung-Ah Sohn(Ajou University), Dokyoon Kim(Geisinger Medical Center), for Alzheimer’s Disease Neuroimaging Initiative(University of California, San Francisco), Michael W. Weiner(University of California, San Francisco), Paul Aisen(University of California San Diego), Ronald Petersen(Mayo Clinic in Arizona), Clifford R. Jack(Berkeley College), William J. Jagust(Berkeley College), John Q. Trojanowki(LAC+USC Medical Center), Arthur W. Toga(LAC+USC Medical Center), Laurel Beckett(Brigham and Women's Hospital), Robert C. Green(Brigham and Women's Hospital), Andrew J. Saykin(Washington University in St. Louis), John C. Morris(Washington University in St. Louis), Leslie M. Shaw(Prevent Alzheimer’s Disease 2020), Zaven S. Khachaturian(Siemens (Germany)), Greg Sorensen(Alzheimer's Association), María C. Carrillo(Alzheimer's Association), Lew Kuller(Washington University in St. Louis), Marc Raichle(Washington University in St. Louis), Steven M. Paul(Albert Einstein College of Medicine), Peter J. Davies(Albert Einstein College of Medicine), Howard Fillit(Alzheimer's Drug Discovery Foundation), Franz Hefti(Washington University in St. Louis), Davie Holtzman(Northwestern University), Marek-Marsel Mesulam(Northwestern University), William Z. Potter(Brown University), Peter J. Snyder(University of Washington), Tom Montine(University of Washington), Ronald G. Thomas(University of California San Diego), Michael Donohue(University of California San Diego), Sarah Walter(University of California San Diego), Tamie Sather(University of California San Diego), Gus Jiminez(University of California San Diego), Archana B. Balasubramanian(University of California San Diego), Jennifer Mason(University of California San Diego), Iris Sim(University of California San Diego), Danielle Harvey(Mayo Clinic in Arizona), Matt A. Bernstein(University of London), Nick C. Fox(University of London), Paul M. Thompson(University of California, San Francisco), Norbert Schuff(University of California, San Francisco), Charles DeCarli(Mayo Clinic in Arizona), Bret Borowski(Mayo Clinic in Arizona), Jeff Gunter(Mayo Clinic in Arizona), Matthew L. Senjem(Mayo Clinic in Arizona), Prashanthi Vemuri(Mayo Clinic in Arizona), David Jones(Mayo Clinic in Arizona), Kejal Kantarci(Mayo Clinic in Arizona), Chad Ward(University of Michigan), Robert A. Koeppe(University of Utah), Norm Foster(Alzheimer's Association), Eric M. Reiman(Alzheimer's Association), Kewei Chen(Alzheimer's Association), Chet Mathis(Berkeley College), Susan Landau(Berkeley College), Nigel J. Cairns(Washington University in St. Louis), Erin Householder(Washington University in St. Louis), Lisa Taylor‐Reinwald(Washington University in St. Louis), Virginia Lee(UCLA Medical Center), Magdalena Korecka(UCLA Medical Center), Michal Figurski(LAC+USC Medical Center), Karen Crawford(LAC+USC Medical Center), Scott Neu(LAC+USC Medical Center), Tatiana M. Foroud(University of California, Irvine), Steven Potkin(University of California, Irvine), Li Shen(Indiana University Bloomington), Kelley Faber(Indiana University Bloomington), Sungeun Kim(Siemens (Germany)), Lean Tha(Siemens (Germany)), Richard Frank(National Institute on Aging), John Hsiao(Oregon Health & Science University), Jeffrey Kaye(Oregon Health & Science University), Joseph F. Quinn(Oregon Health & Science University), Lisa C. Silbert(Oregon Health & Science University), Betty Lind(Oregon Health & Science University), Raina Carter(Oregon Health & Science University), Sara Dolen(Oregon Health & Science University), Beau M. Ances(Washington University in St. Louis), Maria Carroll(Washington University in St. Louis), Mary L. Creech(Washington University in St. Louis), Erin Franklin(Washington University in St. Louis), Mark A. Mintun(Washington University in St. Louis), Stacy Schneider(Washington University in St. Louis), Angela Oliver(LAC+USC Medical Center), Lon S. Schneider(LAC+USC Medical Center), Sonia Pawluczyk(LAC+USC Medical Center), Mauricio Beccera(LAC+USC Medical Center), Liberty Teodoro(LAC+USC Medical Center), Bryan M. Spann(LAC+USC Medical Center), James Brewer(University of California San Diego), Helen Vanderswag(Alzheimer's Association), Adam Fleisher(Alzheimer's Association), Daniel Marson(University of Alabama at Birmingham), Randall Griffith(University of Alabama at Birmingham), David Clark(University of Alabama at Birmingham), David Geldmacher(University of Alabama at Birmingham), John Brockington(University of Alabama at Birmingham), Erik D. Roberson(Johns Hopkins University), Marissa Natelson Love(Berkeley College), Judith L. Heidebrink(Berkeley College), Joanne Lord(Berkeley College), Sara S. Mason(Mayo Clinic in Arizona), Colleen S. Albers(Mayo Clinic in Arizona), David S. Knopman(Mayo Clinic in Arizona), Kris Johnson(Brigham and Women's Hospital), Hillel Grossman(Icahn School of Medicine at Mount Sinai), Effie Mitsis(Rush University Medical Center), Raj C. Shah(Rush University Medical Center), Leyla deToledo‐Morrell(Rush University Medical Center), Rachelle S. Doody(Baylor College of Medicine), Javier Villanueva‐Meyer(Baylor College of Medicine), Munir Chowdhury(Baylor College of Medicine), Susan Rountree(Baylor College of Medicine), Mimi Dang(Baylor College of Medicine), Ranjan Duara, Daniel Varón, Maria T. Greig, Peggy Roberts(Columbia University Irving Medical Center), Yaakov Stern(Columbia University Irving Medical Center), Lawrence S. Honig(Columbia University Irving Medical Center), Karen L. Bell(Johns Hopkins University), Marilyn Albert(Johns Hopkins University), Chiadi U. Onyike(Johns Hopkins University), Daniel D’Agostino(Johns Hopkins University), Stephanie Kielb(Johns Hopkins University), James E. Galvin(New York University), Brittany Cerbone(New York University), Christina A. Michel(New York University), Dana M. Pogorelec(New York University), Henry Rusinek(New York University), Mony J. de Leon(New York University), Lidia Glodzik(New York University), Susan De Santi(New York University), Kyle Womack, Dana Mathews, Mary Quiceno(Duke Medical Center), P. Murali Doraiswamy(Duke Medical Center), Jeffrey R. Petrella(Duke Medical Center), Salvador Borges‐Neto(Duke Medical Center), Terence Z. Wong(Duke Medical Center), Edward Coleman(Emory University), Allan I. Levey(Emory University), James J. Lah(Emory University), Janet S. Cella(Emory University), Jeffrey M. Burns(University of Kansas Medical Center), Russell H. Swerdlow(University of Kansas Medical Center), William M. Brooks(University of Kansas Medical Center), Steven E. Arnold(University of Pennsylvania), Jason Karlawish(University of Pennsylvania), David A. Wolk(University of Pennsylvania), Christopher Clark(UCLA Medical Center), Liana Apostolova(UCLA Medical Center), Kathleen Tingus(UCLA Medical Center), Ellen Woo(UCLA Medical Center), Daniel Silverman(UCLA Medical Center), Po H. Lu(UCLA Medical Center), George Bartzokis(University of Kentucky), Charles D. Smith(University of Kentucky), Gregory A. Jicha(University of Kentucky), Peter Hardy(University of Kentucky), Partha Sinha(University of Kentucky), Elizabeth Oates(University of Kentucky), Gary Conrad(University of Kentucky), Neill R. Graff‐Radford(Jacksonville College), Francine Parfitt(Jacksonville College), Tracy Kendall(Jacksonville College), Heather Johnson(Jacksonville College), Oscar L. López(Pittsburg State University), MaryAnn Oakley(Pittsburg State University), Donna M. Simpson(Indiana University Bloomington), Martin R. Farlow(Indiana University Bloomington), Ann Marie Hake(Indiana University Bloomington), Brandy R. Matthews(Indiana University Bloomington), Jared R. Brosch(Indiana University Bloomington), Scott Herring(Indiana University Bloomington), Cynthia Hunt(University of Rochester Medical Center), Anton P. Porsteinsson(University of Rochester Medical Center), Bonnie S. Goldstein(University of Rochester Medical Center), Kim Martin(University of Rochester Medical Center), Kelly M. Makino(University of Rochester Medical Center), M. Saleem Ismail(University of Rochester Medical Center), Connie Brand(University of Rochester Medical Center), Ruth A. Mulnard(University of Rochester Medical Center), Gaby Thai(University of Rochester Medical Center), Catherine Mc-Adams-Ortiz(University of Rochester Medical Center), Christopher H. van Dyck(Yale University), Richard E. Carson(Yale University), Martha G. MacAvoy(Yale University), Pradeep Varma(Jewish General Hospital), Howard Chertkow(Jewish General Hospital), Howard Bergman(Jewish General Hospital), Chris Hosein(Sunnybrook Health Science Centre), Sandra Black(Sunnybrook Health Science Centre), Bojana Stefanovic(Sunnybrook Health Science Centre), Curtis Caldwell(Sunnybrook Health Science Centre), Ging‐Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly(St Joseph's Health Centre), Elizabeth Finger(St Joseph's Health Centre), Stephen Pasternack(St Joseph's Health Centre), Irina Rachisky(St Joseph's Health Centre), Dick Trost(St Joseph's Health Centre), Andrew Kertesz(Cleveland Clinic), Charles Bernick(Cleveland Clinic), Donna Munic(Northwestern University), Kristine Lipowski(Northwestern University), Masandra Weintraub(Northwestern University), Borna Bonakdarpour(Northwestern University), Diana Kerwin(Northwestern University), Chuang‐Kuo Wu(Northwestern University), Nancy Johnson(Northwestern University), Carl Sadowsky(Palm Beach Neurology), Teresa Villena(Georgetown University), Raymond Scott Turner(Georgetown University), Kathleen Johnson(Brigham and Women's Hospital), Brigid Reynolds(Brigham and Women's Hospital), Reisa A. Sperling(Brigham and Women's Hospital), Keith A. Johnson(Brigham and Women's Hospital), Gad A. Marshall(Brigham and Women's Hospital), Jerome A. Yesavage(Stanford University), Joy L. Taylor(Stanford University), Barton Lane(Stanford University), Allyson Rosen(Stanford University), Jared Tinklenberg(Alzheimer's Association), Marwan N. Sabbagh(Alzheimer's Association), Christine M. Belden(Alzheimer's Association), Sandra A. Jacobson(Alzheimer's Association), Sherye A. Sirrel(Boston University), Neil W. Kowall(Boston University), Ronald Killiany(Boston University), Andrew E. Budson(Boston University), Alexander Norbash(Boston University), Patricia Lynn Johnson(Boston University), Thomas O. Obisesan(Howard University), Saba Wolday(Howard University), Joanne Allard(Howard University), Alan J. Lerner(Case Western Reserve University), Paula Ogrocki(Case Western Reserve University), Curtis Tatsuoka(Case Western Reserve University), Parianne Fatica(Case Western Reserve University), Evan Fletcher(University of California, Davis), Pauline Maillard(University of California, Davis), John Olichney(University of California, Davis), Owen Carmichael(Neurological Surgery), Smita Kittur(St Joseph's Health Care), Michael Borrie(St Joseph's Health Care), T.-Y. Lee(St Joseph's Health Care), Robert Bartha(St Joseph's Health Care), Sterling C. Johnson(St Joseph's Health Care), Sanjay Asthana(St Joseph's Health Care), Cynthia M. Carlsson(University of California, Irvine), Adrian Preda(University of California, Irvine), Dana Nguyen(Alzheimer's Association), Pierre N. Tariot(Alzheimer's Association), Anna Burke(Alzheimer's Association), Nadira Trncic(Alzheimer's Association), Adam Fleisher(Alzheimer's Association), Stephanie Reeder(Alzheimer's Association), Vernice Bates(Dent Neurologic Institute), Horacio Capote(Dent Neurologic Institute), Michelle Rainka(Dent Neurologic Institute), Douglas W. Scharre(The Ohio State University), Maria Kataki(The Ohio State University), Anahita Adeli(The Ohio State University), Earl A. Zimmerman(Albany Medical Center Hospital), Dzintra Celmins(Albany Medical Center Hospital), Alice D. Brown(Hartford Hospital), Godfrey D. Pearlson(Hartford Hospital), Karen Blank(Hartford Hospital), Karen Anderson(Dartmouth–Hitchcock Medical Center), Laura A. Flashman(Dartmouth–Hitchcock Medical Center), Marc Seltzer(Dartmouth–Hitchcock Medical Center), Mary L. Hynes(Dartmouth–Hitchcock Medical Center), Robert B. Santulli(Dartmouth–Hitchcock Medical Center), Kaycee M. Sink(Wake Forest University), Leslie Gordineer(Wake Forest University), Jeff D. Williamson(Wake Forest University), Pradeep Garg(Wake Forest University), Franklin Watkins(Brown University), Brian R. Ott(Brown University), Henry Querfurth(Brown University), Geoffrey Tremont(Brown University), Stephen Salloway(Brown University), Paul Malloy(Brown University), Stephen Correia(University of California, San Francisco), Howard J. Rosen(University of California, San Francisco), Bruce L. Miller(University of California, San Francisco), David C. Perry(Medical University of South Carolina), Jacobo Mintzer(Medical University of South Carolina), Kenneth Spicer(Medical University of South Carolina), David Bachman(Medical University of South Carolina), Elizabeth Finger(St Joseph's Health Centre), Stephen Pasternak(St Joseph's Health Care), Irina Rachinsky(St Joseph's Health Care), John Rogers(St Joseph's Health Care), Dick Drost(Nathan Kline Institute for Psychiatric Research), Nunzio Pomara(Nathan Kline Institute for Psychiatric Research), Raymundo Hernando(Nathan Kline Institute for Psychiatric Research), Antero Sarrael(Nathan Kline Institute for Psychiatric Research), Susan K. Schultz(University of Iowa), Laura L. Boles Ponto(University of Iowa), Hyungsub Shim(University of Iowa), Karen Ekstam Smith(University of Iowa), Norman Relkin(Cornell University), Gloria Chaing(Cornell University), Michael Lin(Cornell University), Lisa Ravdin(Cornell University), Amanda Smith(University of South Florida), Balebail Ashok Raj(University of South Florida), Kristin Fargher(University of South Florida)
Scientific Reports
February 13, 2019
Cited by 398Open Access
Full Text

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.


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