The trend of disruption in the functional brain network topology of Alzheimer’s disease

Authors: Alireza Fathian, Yousef Jamali, Mohammad Reza Raoufy, for the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Norbert Schuf, Howard J. Rosen, Bruce L. Miller, Thomas C. Neylan, Jacqueline Hayes, Shannon Finley, Paul Aisen, Zaven S. Khachaturian, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Leon J. Thal, James B. Brewer, Helen Vanderswag, Adam Fleisher, Melissa Davis, Rosemary Morrison, Ronald Petersen, Cliford R. Jack, Matt A. Bernstein, Bret Borowski, Jef Gunter, Matthew L. Senjem, Prashanthi Vemuri, David T. Jones, Kejal Kantarci, Chad Ward, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, William J. Jagust, Susan Landau, John Q. Trojanowki, Leslie M. Shaw, Virginia Lee, Magdalena Korecka, Michal Figurski, Steven E. Arnold, Jason Karlawish, David A. Wolk, Arthur W. Toga, Karen Crawford, Scott Neu, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, Laurel Beckett, Danielle Harvey, Evan Fletcher, Owen Carmichael, John Olichney, Charles DeCarli, Robert C. Green, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Meghan Frey, Barton Lane, Allyson Rosen, Jared Tinklenberg, Andrew J. Saykin, Tatiana M. Foroud, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Martin R. Farlow, AnnMarie Hake, Brandy R. Matthews, Scott Herring, Cynthia Hunt, John C. Morris, Marc Raichle, Davie Holtzman, Nigel J. Cairns, Erin Householder, Lisa Taylor‐Reinwald, Beau M. Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, Angela Oliver, Lisa Raudin, Greg Sorensen, Lew Kuller, Chet Mathis, Oscar L. Lopez, MaryAnn Oakley, Steven M. Paul, Norman Relkin, Gloria Chaing, Lisa Raudin, Peter Davies, Howard Fillit, Franz Hefti, Marek-Marsel Mesulam, Diana Kerwin, Marek-Marsel Mesulam, Kristine Lipowski, Chuang‐Kuo Wu, Nancy Johnson, Jordan Grafman, William Z. Potter, Peter J. Snyder, Adam J. Schwartz, Tom Montine, Elaine R. Peskind, Nick C. Fox, Paul M. Thompson, Liana G. Apostolova, Kathleen Tingus, Ellen Woo, Daniel Silverman, Po H. Lu, George Bartzokis, Robert A. Koeppe, Judith L. Heidebrink, Joanne Lord, Steven G. Potkin, Adrian Preda, Dana Nguyenv, Norm Foster, Eric M. Reiman, Kewei Chen, Adam Fleisher, Pierre N. Tariot, Stephanie Reeder, Steven G. Potkin, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Neil Buckholtz, John Hsiao, Marylyn Albert, Marilyn Albert, Chiadi U. Onyike, Daniel D’Agostino, Stephanie Kielb, Donna M. Simpson, Richard Frank, Jefrey Kaye, Joseph F. Quinn, Betty Lind, Raina Carter, Sara Dolen, Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Daniel Marson, Randall Grifth, David A. Clark, David Geldmacher, John Brockington, Erik D. Roberson, Hillel Grossman, Efe Mitsis, Leyla de Toledo‐Morrell, Raj C. Shah, Debra Fleischman, Konstantinos Arfanakis, Ranjan Duara, Daniel Varón, Maria T. Greig, Peggy Roberts, James E. Galvin, Brittany Cerbone, Christina A. Michel, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan De Santi, P. Murali Doraiswamy, Jefrey R. Petrella, Terence Z. Wong, Olga James, Charles D. Smith, Gregory A. Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Kyle Womack, Dana Mathews, Mary Quiceno, Ramon Diaz‐Arrastia, Richard King, Myron Weiner, Kristen Martin-Cook, Michael D. Devous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jefrey M. Burns, Heather S. Anderson, Russell H. Swerdlow, Neill R. Graf-Radford, Francine Parftt, Tracy Kendall, Heather Johnson, 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, Andrew Kertesz, John Rogers, Charles Bernick, Donna Munic, Andrew Kertesz, Andrew Kertesz, John Rogers, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, Dick Drost, Carl Sadowsky, Walter Martínez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Joanne Allard, Alan J. Lerner, Paula Ogrocki, Leon Hudson, Smita Kittur, Michael Borrie, T‐Y Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, J. Jay Fruehling, Sandra Harding, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Eric C. Petrie, Gail Li, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Robert B. Santulli, Tamar J. Kitzmiller, Eben S. Schwartz, Kaycee M. Sink, Jef D. Williamson, Pradeep Kumar Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geofrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Jacobo Mintzer, Kenneth Spicer, David Bachman, Dino Massoglia, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Laura L. Boles Ponto, Hyungsub Shim, Karen E. Smith, Amanda Smith, Kristin Fargher, Balebail Ashok Raj, Karl E. Friedl, Jerome A. Yesavage, Joy L. Taylor, Ansgar J. Furst - Scientific Reports 2022 cited by 41

Alzheimer's disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain's functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer's disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process.