Abstract

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).

Details

Title
Cascaded Multi-view Canonical Correlation (CaMCCo) for Early Diagnosis of Alzheimer’s Disease via Fusion of Clinical, Imaging and Omic Features
Author
Singanamalli, Asha 1 ; Wang, Haibo 1 ; Madabhushi, Anant 1 ; Weiner, Michael 2 ; Aisen, Paul 3 ; Petersen, Ronald 4 ; Clifford, Jack 5 ; Jagust, William 6 ; Trojanowki, John 7 ; Toga, Arthur 8 ; Beckett, Laurel 9 ; Green, Robert 10 ; Saykin, Andrew 11 ; Morris, John 12 ; Shaw, Leslie 12 ; Kaye, Jeffrey 13 ; Quinn, Joseph 13 ; Silbert, Lisa 13 ; Lind, Betty 13 ; Carter, Raina 13 ; Dolen, Sara 13 ; Schneider, Lon 8 ; Pawluczyk, Sonia 8 ; Beccera, Mauricio 8 ; Liberty Teodoro 8 ; Spann, Bryan 8 ; Brewer, James 14 ; Vanderswag, Helen 14 ; Fleisher, Adam 14 ; Heidebrink, Judith 15 ; Lord, Joanne 15 ; Mason, Sara 5 ; Albers, Colleen 5 ; Knopman, David 5 ; Johnson, Kris 5 ; Doody, Rachelle 16 ; Villanueva-Meyer, Javier 16 ; Chowdhury, Munir 16 ; Rountree, Susan 16 ; Dang, Mimi 16 ; Stern, Yaakov 17 ; Honig, Lawrence 17 ; Bell, Karen 17 ; Ances, Beau 12 ; Carroll, Maria 12 ; Creech, Mary 2 ; Franklin, Erin 12 ; Mintun, Mark 12 ; Schneider, Stacy 12 ; Oliver, Angela 12 ; Marson, Daniel 18 ; Griffith, Randall 18 ; Clark, David 18 ; Geldmacher, David 18 ; Brockington, John 18 ; Roberson, Erik 18 ; Marissa Natelson Love 18 ; Grossman, Hillel 19 ; Mitsis, Effie 19 ; Shah, Raj 20 ; deToledo-Morrell, Leyla 20 ; Duara, Ranjan 21 ; Varon, Daniel 21 ; Greig, Maria 21 ; Roberts, Peggy 21 ; Albert, Marilyn 22 ; Onyike, Chiadi 22 ; Daniel D’Agostino 22 ; Kielb, Stephanie 22 ; Galvin, James 23 ; Cerbone, Brittany 23 ; Michel, Christina 23 ; Pogorelec, Dana 23 ; Rusinek, Henry 23 ; Mony de Leon 23 ; Glodzik, Lidia 23 ; De Santi, Susan 23 ; Doraiswamy, P 24 ; Petrella, Jeffrey 24 ; Borges-Neto, Salvador 24 ; Wong, Terence 24 ; Coleman, Edward 24 ; Smith, Charles 25 ; Jicha, Greg 25 ; Hardy, Peter 25 ; Sinha, Partha 25 ; Oates, Elizabeth 25 ; Conrad, Gary 25 ; Porsteinsson, Anton 26 ; Goldstein, Bonnie 26 ; Kim, Martin 26 ; Makino, Kelly 26 ; Ismail, M 26 ; Brand, Connie 26 ; Mulnard, Ruth 27 ; Thai, Gaby 27 ; Mc-Adams-Ortiz, Catherine 27 ; Womack, Kyle 28 ; Mathews, Dana 28 ; Quiceno, Mary 28 ; Levey, Allan 29 ; Lah, James 29 ; Cellar, Janet 29 ; Burns, Jeffrey 30 ; Swerdlow, Russell 30 ; Brooks, William 30 ; Apostolova, Liana 31 ; Tingus, Kathleen 31 ; Woo, Ellen 31 ; Silverman, Daniel 31 ; Lu, Po 31 ; Bartzokis, George 31 ; Graff-Radford, Neill 32 ; Parfitt, Francine 32 ; Kendall, Tracy 32 ; Johnson, Heather 32 ; Farlow, Martin 11 ; Hake, Ann Marie 11 ; Matthews, Brandy 11 ; Brosch, Jared 11 ; Herring, Scott 11 ; Hunt, Cynthia 11 ; Dyck, Christopher 33 ; Carson, Richard 33 ; MacAvoy, Martha 33 ; Varma, Pradeep 33 ; Chertkow, Howard 34 ; Bergman, Howard 34 ; Hosein, Chris 34 ; Black, Sandra 35 ; Stefanovic, Bojana 35 ; Caldwell, Curtis 35 ; Hsiung, Ging-Yuek Robin 36 ; Feldman, Howard 36 ; Mudge, Benita 36 ; Assaly, Michele 36 ; Finger, Elizabeth 37 ; Pasternack, Stephen 37 ; Rachisky, Irina 37 ; Trost, Dick 37 ; Kertesz, Andrew 37 ; Bernick, Charles 38 ; Munic, Donna 38 ; Marek-Marsel Mesulam 39 ; Lipowski, Kristine 39 ; Weintraub, Sandra 39 ; Bonakdarpour, Borna 39 ; Kerwin, Diana 39 ; Chuang-Kuo, Wu 39 ; Johnson, Nancy 39 ; Sadowsky, Carl 40 ; Villena, Teresa 40 ; Turner, Raymond Scott 41 ; Johnson, Kathleen 41 ; Reynolds, Brigid 41 ; Sperling, Reisa 42 ; Johnson, Keith 42 ; Marshall, Gad 42 ; Yesavage, Jerome 43 ; Taylor, Joy 43 ; Lane, Barton 43 ; Rosen, Allyson 43 ; Tinklenberg, Jared 43 ; Sabbagh, Marwan 44 ; Belden, Christine 44 ; Jacobson, Sandra 44 ; Sirrel, Sherye 44 ; Kowall, Neil 45 ; Killiany, Ronald 45 ; Budson, Andrew 45 ; Norbash, Alexander 45 ; Johnson, Patricia Lynn 45 ; Obisesan, Thomas 46 ; Wolday, Saba 46 ; Allard, Joanne 46 ; Lerner, Alan 47 ; Ogrocki, Paula 47 ; Tatsuoka, Curtis 47 ; Fatica, Parianne 47 ; Fletcher, Evan 48 ; Maillard, Pauline 48 ; Olichney, John 48 ; DeCarli, Charles 48 ; Carmichael, Owen 48 ; Kittur, Smita 49 ; Borrie, Michael 50 ; T-Y, Lee 50 ; RobBartha 50 ; Johnson, Sterling 51 ; Asthana, Sanjay 51 ; Carlsson, Cynthia 51 ; Potkin, Steven 52 ; Preda, Adrian 52 ; Nguyen, Dana 52 ; Tariot, Pierre 53 ; Burke, Anna 53 ; Trncic, Nadira 53 ; Reeder, Stephanie 53 ; Bates, Vernice 54 ; Capote, Horacio 54 ; Rainka, Michelle 54 ; Scharre, Douglas 55 ; Kataki, Maria 55 ; Adeli, Anahita 55 ; Zimmerman, Earl 56 ; Celmins, Dzintra 56 ; Brown, Alice 56 ; Pearlson, Godfrey 57 ; Blank, Karen 57 ; Anderson, Karen 57 ; Flashman, Laura 58 ; Seltzer, Marc 58 ; Hynes, Mary 58 ; Santulli, Robert 58 ; Sink, Kaycee 59 ; Gordineer, Leslie 59 ; Williamson, Jeff 59 ; Garg, Pradeep 59 ; Watkins, Franklin 59 ; Ott, Brian 60 ; Querfurth, Henry 60 ; Tremont, Geoffrey 60 ; Salloway, Stephen 61 ; Malloy, Paul 61 ; Correia, Stephen 61 ; Rosen, Howard 62 ; Miller, Bruce 62 ; Perry, David 62 ; Mintzer, Jacobo 63 ; Spicer, Kenneth 63 ; Bachman, David 63 ; Pomara, Nunzio 64 ; Hernando, Raymundo 65 ; Sarrael, Antero 64 ; Relkin, Norman 65 ; Chaing, Gloria 65 ; Lin, Michael 65 ; Ravdin, Lisa 65 ; Smith, Amanda 66 ; Balebail, Ashok Raj 66 ; Fargher, Kristin 66 

 Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA 
 Magnetic Resonance Unit at the VA Medical Center and Radiology, Medicine, Psychiatry and Neurology, University of California, San Francisco, USA 
 San Diego School of Medicine, University of California, California, USA 
 Mayo Clinic, Minnesota, USA 
 Mayo Clinic, Rochester, USA 
 University of California, Berkeley, USA 
 University of Pennsylvania, Pennsylvania, USA 
 University of Southern California, California, USA 
 University of California, Davis, California, USA 
10  MPH Brigham and Women’s Hospital/Harvard Medical School, Massachusetts, USA 
11  Indiana University, Indiana, USA 
12  Washington University St. Louis, Missouri, USA 
13  Oregon Health and Science University, Oregon, USA 
14  University of California–San Diego, California, USA 
15  University of Michigan, Michigan, USA 
16  Baylor College of Medicine, Houston, State of Texas, USA 
17  Columbia University Medical Center, South Carolina, USA 
18  University of Alabama – Birmingham, Alabama, USA 
19  Mount Sinai School of Medicine, New York, USA 
20  Rush University Medical Center, Rush University, Illinois, USA 
21  Wien Center, Florida, USA 
22  Johns Hopkins University, Maryland, USA 
23  New York University, NY, USA 
24  Duke University Medical Center, North Carolina, USA 
25  University of Kentucky, Kentucky, USA 
26  University of Rochester Medical Center, NY, USA 
27  University of California, California, USA 
28  University of Texas Southwestern Medical School, Texas, USA 
29  Emory University, Georgia, USA 
30  University of Kansas, Medical Center, Kansas, USA 
31  University of California, Los Angeles, California, USA 
32  Mayo Clinic, Jacksonville, Jacksonville, USA 
33  Yale University School of Medicine, Connecticut, USA 
34  McGill University, Montreal-Jewish General Hospital, Montreal, Canada 
35  Sunnybrook Health Sciences, Ontario, USA 
36  U.B.C. Clinic for AD & Related Disorders, Vancouver, BC, Canada 
37  Cognitive Neurology - St. Joseph’s, Ontario, USA 
38  Cleveland Clinic Lou Ruvo Center for Brain Health, Ohio, USA 
39  Northwestern University, San Francisco, USA 
40  Premiere Research Inst (Palm Beach Neurology), west Palm Beach, USA 
41  Georgetown University Medical Center, Washington DC, USA 
42  Brigham and Women’s Hospital, Massachusetts, USA 
43  Stanford University, California, USA 
44  Banner Sun Health Research Institute, Sun City, USA 
45  Boston University, Massachusetts, USA 
46  Howard University, Washington DC, USA 
47  Case Western Reserve University, Ohio, USA 
48  University of California, Davis – Sacramento, California, USA 
49  Neurological Care of CNY, Liverpool, USA 
50  Parkwood Hospital, Pennsylvania, USA 
51  University of Wisconsin, Wisconsin, USA 
52  University of California, Irvine – BIC, USA 
53  Banner Alzheimer’s Institute, Phoenix, USA 
54  Dent Neurologic Institute, NY, USA 
55  Ohio State University, Ohio, USA 
56  Albany Medical College, NY, USA 
57  Hartford Hospital, Olin Neuropsychiatry Research Center, Connecticut, USA 
58  Dartmouth-Hitchcock Medical Center, New Hampshire, USA 
59  Wake Forest University Health Sciences, North Carolina, USA 
60  Rhode Island Hospital, state of Rhode Island, Providence, USA 
61  Butler Hospital, Providence, Rhode Island, USA 
62  University of California, San Francisco, USA 
63  Medical University South Carolina, Charleston, USA 
64  Nathan Kline Institute, Orangeburg, New York, USA 
65  Cornell University, Ithaca, New York, USA 
66  USF Health Byrd Alzheimer’s Institute, University of South Florida, Tampa, USA 
Pages
1-14
Publication year
2017
Publication date
Aug 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1957229621
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.