Cascaded Multi-view Canonical Correlation (CaMCCo) for Early Diagnosis of Alzheimer’s Disease via Fusion of Clinical, Imaging and Omic Features
Authors: Singanamalli Asha , Wang Haibo , Madabhushi Anant ,   Alzheimer’s Disease Neuroimaging Initiative, Weiner Michael , Aisen Paul , Petersen Ronald , Jack Clifford , Jagust William , Trojanowki John , Toga Arthur , Beckett Laurel , Green Robert , Saykin Andrew , Morris John , Shaw Leslie , Kaye Jeffrey , Quinn Joseph , Silbert Lisa , Lind Betty , Carter Raina , Dolen Sara , Schneider Lon , Pawluczyk Sonia , Beccera Mauricio , Teodoro Liberty , Spann Bryan , Brewer James , Vanderswag Helen , Fleisher Adam , Heidebrink Judith , Lord Joanne , Mason Sara , Albers Colleen , Knopman David , Johnson Kris , Doody Rachelle , Villanueva-Meyer Javier , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence , Bell Karen , Ances Beau , Morris John , Carroll Maria , Creech Mary , Franklin Erin , Mintun Mark , Schneider Stacy , Oliver Angela , Marson Daniel , Griffith Randall , Clark David , Geldmacher David , Brockington John , Roberson Erik , Natelson Love Marissa , Grossman Hillel , Mitsis Effie , Shah Raj , deToledo-Morrell Leyla , Duara Ranjan , Varon Daniel , Greig Maria , Roberts Peggy , Albert Marilyn , Onyike Chiadi , D’Agostino Daniel , Kielb Stephanie , Galvin James , Cerbone Brittany , Michel Christina , Pogorelec Dana , Rusinek Henry , de Leon Mony , Glodzik Lidia , De Santi Susan , Doraiswamy P. , Petrella Jeffrey , Borges-Neto Salvador , Wong Terence , Coleman Edward , Smith Charles , Jicha Greg , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , Porsteinsson Anton , Goldstein Bonnie , Martin Kim , Makino Kelly , Ismail M. , Brand Connie , Mulnard Ruth , Thai Gaby , Mc-Adams-Ortiz Catherine , Womack Kyle , Mathews Dana , Quiceno Mary , Levey Allan , Lah James , Cellar Janet , Burns Jeffrey , Swerdlow Russell , Brooks William , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel , Lu Po , Bartzokis George , Graff-Radford Neill , Parfitt Francine , Kendall Tracy , Johnson Heather , Farlow Martin , Marie Hake Ann , Matthews Brandy , Brosch Jared , Herring Scott , Hunt Cynthia , Dyck Christopher , Carson Richard , MacAvoy Martha , Varma Pradeep , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Robin Hsiung Ging-Yuek , Feldman Howard , Mudge Benita , Assaly Michele , Finger Elizabeth , Pasternack Stephen , Rachisky Irina , Trost Dick , Kertesz Andrew , Bernick Charles , Munic Donna , Mesulam Marek-Marsel , Lipowski Kristine , Weintraub Sandra , Bonakdarpour Borna , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Sadowsky Carl , Villena Teresa , Scott Turner Raymond , Johnson Kathleen , Reynolds Brigid , Sperling Reisa , Johnson Keith , Marshall Gad , Yesavage Jerome , Taylor Joy , Lane Barton , Rosen Allyson , Tinklenberg Jared , Sabbagh Marwan , Belden Christine , Jacobson Sandra , Sirrel Sherye , Kowall Neil , Killiany Ronald , Budson Andrew , Norbash Alexander , Lynn Johnson Patricia , Obisesan Thomas , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Fletcher Evan , Maillard Pauline , Olichney John , DeCarli Charles , Carmichael Owen , Kittur Smita , Borrie Michael , Lee T-Y , RobBartha  , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia , Potkin Steven , Preda Adrian , Nguyen Dana , Tariot Pierre , Burke Anna , Trncic Nadira , Fleisher Adam , Reeder Stephanie , Bates Vernice , Capote Horacio , Rainka Michelle , Scharre Douglas , Kataki Maria , Adeli Anahita , Zimmerman Earl , Celmins Dzintra , Brown Alice , Pearlson Godfrey , Blank Karen , Anderson Karen , Flashman Laura , Seltzer Marc , Hynes Mary , Santulli Robert , Sink Kaycee , Gordineer Leslie , Williamson Jeff , Garg Pradeep , Watkins Franklin , Ott Brian , Querfurth Henry , Tremont Geoffrey , Salloway Stephen , Malloy Paul , Correia Stephen , Rosen Howard , Miller Bruce , Perry David , Mintzer Jacobo , Spicer Kenneth , Bachman David , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Relkin Norman , Chaing Gloria , Lin Michael , Ravdin Lisa , Smith Amanda , Ashok Raj Balebail , Fargher Kristin 
Published: August 2017

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).