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

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.