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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).
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1 Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
2 Magnetic Resonance Unit at the VA Medical Center and Radiology, Medicine, Psychiatry and Neurology, University of California, San Francisco, USA
3 San Diego School of Medicine, University of California, California, USA
4 Mayo Clinic, Minnesota, USA
5 Mayo Clinic, Rochester, USA
6 University of California, Berkeley, USA
7 University of Pennsylvania, Pennsylvania, USA
8 University of Southern California, California, USA
9 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