A deep learning framework identifies dimensional representations of Alzheimer’s Disease from brain structure

作者：Zhijian Yang, Ilya M. Nasrallah, Haochang Shou, Junhao Wen, Jimit J. Doshi, Mohamad Habes, Güray Erus, Ahmed Abdulkadir, Susan M. Resnick, Marilyn S. Albert, Paul T. Maruff, Jürgen Fripp, John C. Morris, David A. Wolk, Christos A. Davatzikos, Yong Fan, Vishnu Bashyam, Elizabeth Mamouiran, Randa Melhem, Raymond Pomponio, Dushyant Sahoo, Ashish Singh, Ioanna Skampardoni, Lasya P Sreepada, Dhivya Srinivasan, Fanyang Yu, Sindhuja Govindarajan Tirumalai, Yuhan Cui, Zhen Zhou, Katharina Wittfeld, Hans Jörgen Grabe, Duygu Tosun, Murat Bilgel, Yang An, Daniel S. Marcus, Pamela LaMontagne, Susan R. Heckbert, Thomas R. Austin, Lenore J. Launer, Aristeidis Sotiras, Mark Andrew Espeland, Colin Louis Masters, Henry Völzk, Sterling C. Johnson, Luigi Ferrucci, Robert Nick Bryan, Baltimore Longitudinal Study of Aging (BLSA), Alzheimer’s Disease Neuroimaging Initiative (ADNI), Michael Walter Weiner, Paul S. S. Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel A. Beckett, Robert C. Green, Andrew J. Saykin, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah J. Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Jenine Harvey, Matt A. Bernstein, Nick C. Fox, Paul M. Thompson, Norbert W. Schuff, Charles D. DeCarli, Bret Borowski, Jeff L. Gunter, Matthew L. Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan M. Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor‐Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen L. Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley M. Faber, Sungeun Kim, Kwangsik T. Nho, Zaven Kachaturian, Richard A. Frank, Peter Jeffrey Snyder, Susan E. Molchan, JEFFREY A. KAYE, Joseph G. Quinn, Betty Lind, Raina Carter, Sara Dolen, Lon S. S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James B. Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Rachelle Smith Doody, Javier Villanueva Meyer, Munir H. Chowdhury, Susan D. Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau M. Ances, Maria B. Carroll, Sue Leon, Erin Householder, Mark A. Mintun, Stacy Schneider, Angela OliverNG, Randall Griffith, David Clark, David Geldmacher, John C. Brockington, Erik D. Roberson, Hillel T. Grossman, Effie M. Mitsis, Leyla deToledo‐Morrell, Raj C. Shah, Ranjan Duara, Daniel Varón, Maria T. Greig, Peggy Roberts, Marilyn S. Albert, Chiadi U. Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Dana M. Pogorelec, Brittany Cerbone, Christina A. Michel, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan De Santi, Pudugramam Murali Doraiswamy, Jeffrey R. Petrella, Terence Z. Wong, Steven Edward Arnold, Jason H. Karlawish, Charles David Smith, Gregory A. Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby T. Thai, Catherine Mc Adams Ortiz, Kyle B. Womack, Dana Mathews, Mary Ellen Quiceno, Ramon Diaz Arrastia, Richard King, Myron Weiner, Kristen Martin Cook, Michael D. Devous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey Murray Burns, Heather S. Anderson, Russell Howard Swerdlow, Liana G. Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R. Graff Radford, Francine ParfittH, Tracy Kendall, Heather K. Johnson, Martin Rhys Farlow, Ann Marie Hake, Brandy R. Matthews, Scott Herring, Cynthia Hunt, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra E. Black, Bojana Stefanovic, Curtis Caldwell, Ging‐Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly Past, ANDREW E. KERTESZ, John Rogers, Dick Trost, Charles B. Bernick, Donna Munic, Diana R. Kerwin, Marek-Marsel Mesulam, Kristine Lipowski, Chuang Kuo Wu, Nancy E. Johnson, Carl Sadowsky, Walter Fabián Martínez, Teresa Villena, Raymond Scott Turner, Kathleen B. Johnson, Brigid Reynolds, Reisa Anne Sperling, Keith A. Johnson, Gad A. Marshall, Meghan T Frey, Jerome Albert Yesavage, Joy L. Taylor, Barton Lane, Allyson C Rosen, Jared R. Tinklenberg, Marwan Noel Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas Olabode Obisesan, Saba Wolday, Joanne S. Allard, Alan Jay Lerner, Paula K. Ogrocki, Leon Hudson, Evan M. Fletcher, Owen Thomas Carmichael, John Olichney, Charles D. DeCarli, Smita Kittur, MICHAEL J. BORRIE, T. Y. Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana R. Nguyen, Pierre N. Tariot, Adam Fleisher, Stephanie Reeder, Vernice E. Bates, Horacio A. Capote, Michelle M. Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra F. Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Robert B. Santulli, Tamar J. Kitzmiller, Eben S. Schwartz, Kaycee M. SinkS, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry W. Querfurth, Geoffrey N. Tremont, Stephen Salloway, Paul F. Malloy, Stephen Correia, Howard J. Rosen, Bruce Leonard Miller, Jacobo E Mintzer, KENNETH M. SPICER, David Bachman, Elizabeth C. Finger, Stephen Pasternak, Irina Rachinsky, John Rogers, ANDREW E. KERTESZ, Dick J. Drost, Nunzio Pomara, Raymundo T. Hernando, Antero Sarrael, Susan K. Schultz, Laura L. Boles Ponto, Hyungsub Shim, Karen Elizabeth Smith, Norman R. Relkin, Gloria Chaing, Lisa Raudin, Amanda D. Smith, Kristin Fargher, Balebail Ashok Raj · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-021-26703-z · 被引用次数：108 · 研究领域：Functional Brain Connectivity Studies、Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a semi-supervised deep-clustering method, which examines neuroanatomical heterogeneity contrasted against normal brain structure, to identify disease subtypes through neuroimaging signatures. When applied to regional volumes derived from T1-weighted MRI (two studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified four patterns or axes of neurodegeneration. Applying this framework to longitudinal data revealed two distinct progression pathways. Measures of expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered complementary performance to amyloid/tau in predicting clinical progression. These deep-learning derived biomarkers offer potential for precision diagnostics and targeted clinical trial recruitment.