Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease
Authors: Gonneaud Julie , Baria Alex T. , Pichet Binette Alexa , Gordon Brian A. , Chhatwal Jasmeer P. , Cruchaga Carlos , Jucker Mathias , Levin Johannes , Salloway Stephen , Farlow Martin , Gauthier Serge , Benzinger Tammie L. S. , Morris John C. , Bateman Randall J. , Breitner John C. S. , Poirier Judes , Vachon-Presseau Etienne , Villeneuve Sylvia ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner Michael , Rosen Howard J. , Miller Bruce L. , Aisen Paul , Thomas Ronald G. , Donohue Michael , Walter Sarah , Gessert Devon , Sather Tamie , Jiminez Gus , Petersen Ronald , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , 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. , Toga Arthur W. , Crawford Karen , Neu Scott , Beckett Laurel , Harvey Danielle , DeCarli Charles , Green Robert C. , Saykin Andrew J. , Foroud Tatiana M. , Shen Li , Kelley Faber , Kim Sungeun , Nho Kwangsik , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Herring Scott , Hunt Cynthia , Cairns Nigel J. , Householder Erin , Reinwald Lisa Taylor , Shaw Leslie M. , Arnold Steven E. , Karlawish Jason H. , Wolk David , Liu Enchi , Montine Tom , Fox Nick , Thompson Paul , Schuff Norbert , Koeppe Robert A. , Heidebrink Judith L. , Lord Joanne L. , Foster Norm , Reiman Eric M. , Chen Kewei , Fleisher Adam , Tariot Pierre , Reeder Stephanie , Mathis Chet , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. , Lee Virginia , Korecka Magdalena , Figurski Michal , Potkin Steven , Kachaturian Zaven , Frank Richard , Snyder Peter J. , Molchan Susan , Kaye Jeffrey , Quinn Joseph , Lind Betty , Carter Raina , Dolen Sara , Schneider Lon S. , Pawluczyk Sonia , Beccera Mauricio , Teodoro Liberty , Spann Bryan M. , Brewer James , Vanderswag Helen , Doody Rachelle S. , Meyer Javier Villanueva , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Morris John , Ances Beau , Carroll Maria , Leon Sue , Mintun Mark A. , Schneider Stacy , OliverNG Angela , Griffith Randall , Clark David , Geldmacher David , Brockington John , Roberson Erik , Grossman Hillel , Mitsis Effie , deToledo-Morrell Leyla , Shah Raj C. , Duara Ranjan , Varon Daniel , Greig Maria T. , Roberts Peggy , Albert Marilyn , Onyike Chiadi , D’Agostino Daniel , Kielb Stephanie , Galvin James E. , Pogorelec Dana M. , Cerbone Brittany , Michel Christina A. , Rusinek Henry , de Leon Mony J. , Glodzik Lidia , De Santi Susan , Doraiswamy P. Murali , Petrella Jeffrey R. , Wong Terence Z. , 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 , Mulnard Ruth A. , Thai Gaby , Mc Adams Ortiz Catherine , Womack Kyle , Mathews Dana , Quiceno Mary , Arrastia Ramon Diaz , King Richard , Weiner Myron , Cook Kristen Martin , DeVous Michael , Levey Allan I. , Lah James J. , Cellar Janet S. , Burns Jeffrey M. , Anderson Heather S. , Swerdlow Russell H. , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H. S. , Lu Po H. , Bartzokis George , Radford Neill R. Graff , ParfittH Francine , Kendall Tracy , Johnson Heather , van Dyck Christopher H. , 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 , Past Michele Assaly , Kertesz Andrew , Rogers John , Trost Dick , Bernick Charles , Munic Donna , Kerwin Diana , Mesulam Marek Marsel , Lipowski Kristine , Wu Chuang Kuo , Johnson Nancy , Sadowsky Carl , Martinez Walter , Villena Teresa , Turner Raymond Scott , Johnson Kathleen , Reynolds Brigid , Sperling Reisa A. , Johnson Keith A. , Marshall Gad , Frey Meghan , Yesavage Jerome , Taylor Joy L. , Lane Barton , Rosen Allyson , Tinklenberg Jared , Sabbagh Marwan N. , Belden Christine M. , Jacobson Sandra A. , Sirrel Sherye A. , Kowall Neil , Killiany Ronald , Budson Andrew E. , Norbash Alexander , Johnson Patricia Lynn , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Hudson Leon , Fletcher Evan , Carmichael Owen , Olichney John , Kittur Smita , Borrie Michael , Lee T. Y. , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Potkin Steven G. , Preda Adrian , Nguyen Dana , Bates Vernice , Capote Horacio , Rainka Michelle , Scharre Douglas W. , Kataki Maria , Adeli Anahita , Zimmerman Earl A. , Celmins Dzintra , Brown Alice D. , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Santulli Robert B. , Kitzmiller Tamar J. , Schwartz Eben S. , Sinks Kaycee M. , Williamson Jeff D. , Garg Pradeep , Watkins Franklin , Ott Brian R. , Querfurth Henry , Tremont Geoffrey , Salloway Stephen , Malloy Paul , Correia Stephen , Mintzer Jacobo , Spicer Kenneth , Bachman David , Finger Elizabether , Pasternak Stephen , Rachinsky Irina , Drost Dick , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Schultz Susan K. , Ponto Laura L. Boles , Shim Hyungsub , Smith Karen Elizabeth , Relkin Norman , Chaing Gloria , Raudin Lisa , Smith Amanda , Fargher Kristin , Raj Balebail Ashok ,   Dominantly Inherited Alzheimer Network (DIAN) Study Group, Allegri Ricardo , Bateman Randy , Bechara Jacob , Benzinger Tammie , Berman Sarah , Bodge Courtney , Brandon Susan , Brooks William , Buck Jill , Buckles Virginia , Chea Sochenda , Chhatwal Jasmeer , Chrem Patricio , Chui Helena , Cinco Jake , Donahue Tamara , Douglas Jane , Edigo Noelia , Erekin-Taner Nilufer , Fagan Anne , Farlow Marty , Fitzpatrick Colleen , Flynn Gigi , Franklin Erin , Fujii Hisako , Gant Cortaiga , Gardener Samantha , Ghetti Bernardino , Goate Alison , Goldman Jill , Gordon Brian , Graff-Radford Neill , Gray Julia , Groves Alexander , Hassenstab Jason , Hoechst-Swisher Laura , Holtzman David , Hornbeck Russ , DiBari Siri Houeland , Ikeuchi Takeshi , Ikonomovic Snezana , Jack Clifford , Jerome Gina , Karch Celeste , Kasuga Kensaku , Kawarabayashi Takeshi , Klunk William , Koeppe Robert , Kuder-Buletta Elke , Laske Christoph , Lee Jae-Hong , Levey Allan , Martins Ralph , Mason Neal Scott , Masters Colin , Maue-Dreyfus Denise , McDade Eric , Mori Hiroshi , Morris John , Nagamatsu Akem , Neimeyer Katie , Noble James , Norton Joanne , Perrin Richard , Raichle Marc , Renton Alan , Ringman John , Roh Jee Hoon , Shimada Hiroyuki , Sigurdson Wendy , Sohrabi Hamid , Sparks Paige , Suzuki Kazushi , Taddei Kevin , Wang Peter , Xiong Chengjie , Xu Xiong ,   Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT-AD) Research Group, Bellec Pierre , Bohbot Véronique , Chakravarty Mallar , Collins Louis , Etienne Pierre , Evans Alan , Gauthier Serge , Hoge Rick , Ituria-Medina Yasser , Nair Vasavan , Near Jamie , Rajah Natasha , Rosa-Neto Pedro , Tardif Christine , Tremblay-Mercier Jennifer , Vachon-Presseau Etienne 
Published: September 2021

Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18–94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology.