Prediction and Classification of Alzheimer’s Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers

Yubraj Gupta, Ramesh Kumar Lama, Goo-Rak Kwon, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Robert C. Green, Tom Montine, Ronald Petersen, Paul Aisen, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Laurel Beckett, Danielle Harvey, Michael Donohue, Clifford R. Jack, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, William Jagust, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Leslie M. Shaw, John Q. Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W. Toga, Karen Crawford, Scott Neu, Andrew J. Saykin, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W. Weiner, Lean Thal, Zaven Khachaturian, Leon Thal, Neil Buckholtz, Michael W. Weiner, Peter J. Snyder, William Potter, Steven Paul, Marilyn Albert, Richard Frank, Zaven Khachaturian, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Ronald Petersen, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, John C. Morris, Maria Carroll, Mary L. Creech, Erin Franklin, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Marilyn Albert, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, John Rogers, Andrew Kertesz, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Michael W. Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Robert C. Green, Danielle Harvey, Clifford R. Jack, William Jagust, John C. Morris, Andrew J. Saykin, Leslie M. Shaw, Arthur W. Toga, John Q. Trojanowki, Thomas Neylan, Jordan Grafman, Robert C. Green, Tom Montine, Michael Weiner, Ronald Petersen, Paul Aisen, Ronald G. Thomas, Michael Donohue, Gessert Devon, Tamie Sather, Davis Melissa, Rosemary Morrison, Gus Jiminez, Thomas Neylan, Hayes Jacqueline, Finley Shannon, Danielle Harvey, Michael Donohue, Clifford R. Jack, Matthew Bernstein, Bret Borowski, Jeff Gunter, Matt Senjem, Kantarci Kejal, Ward Chad, William Jagust, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Householder, Leslie M. Shaw, John Q. Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W. Toga, Crawford Karen, Neu Scott, Andrew J. Saykin, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W. Weiner, Friedl Karl, Lon S. Schneider, Sonia Pawluczyk, Becerra Mauricio, James Brewer, Helen Vanderswag, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Debra Fleischman, Konstantinos Arfanakis, Raj C. Shah, Ranjan Duara, Daniel Varon, Maria T Greig, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Anton P. Porsteinsson, Bonnie Goldstein, Kimberly S. Martin, Steven G. Potkin, Adrian Preda, Dana Nguyen, Jacobo Mintzer, Dino Massoglia, Olga Brawman-Mintzer, Carl Sadowsky, Walter Martinez, Teresa Villena, William Jagust, Susan Landau, Howard Rosen, David Perry, Raymond Scott Turner, Kelly Behan, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Marwan N. Sabbagh, Sandra A. Jacobson, Sherye A. Sirrel, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Joy L. Taylor, Ansgar J. Furst, Steven Chao, Norman Relkin, Gloria Chiang, Lisa Ravdin, Lisa Ravdin, Scott Mackin, Paul Aisen, Rema Raman, Scott Mackin, Michael Weiner, Paul Aisen, Rema Raman, Clifford R. Jack, Susan Landau, Andrew J. Saykin, Arthur W. Toga, Charles DeCarli, Robert A. Koeppe, Robert C. Green, Erin Drake, Michael Weiner, Paul Aisen, Rema Raman, Mike Donohue, Gustavo Jimenez, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Elizabeth Shaffer, Scott Mackin, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Clifford R. Jack, Matthew Bernstein, Bret Borowski, Jeff Gunter, Matt Senjem, Kejal Kantarci, Chad Ward, Denise Reyes, Robert A. Koeppe, Susan Landau, Arthur W. Toga, Karen Crawford, Scott Neu, Andrew J. Saykin, Tatiana M. Foroud, Kelley M. Faber, Kwangsik Nho, Kelly N. Nudelman, Scott Mackin, Howard Rosen, Craig Nelson, David Bickford, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, Dariella Fernandez, Meryl Butters, Michelle Zmuda, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.