Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease
Authors: Zhang Xiuming , Mormino Elizabeth C. , Sun Nanbo , Sperling Reisa A. , Sabuncu Mert R. , Yeo B. T. Thomas ,   the Alzheimer’s Disease Neuroimaging Initiative, Weiner Michael W. , Aisen Paul , Weiner Michael , Aisen Paul , Petersen Ronald , Jack Clifford R. , Jagust William , Trojanowki John Q. , Toga Arthur W. , Beckett Laurel , Green Robert C. , Saykin Andrew J. , Morris John , Shaw Leslie M. , Khachaturian Zaven , Sorensen Greg , Carrillo Maria , Kuller Lew , Raichle Marc , Paul Steven , Davies Peter , Fillit Howard , Hefti Franz , Holtzman David , Mesulam M. Marcel , Potter William , Snyder Peter , Schwartz Adam , Green Robert C. , Montine Tom , Petersen Ronald , Aisen Paul , Thomas Ronald G. , Donohue Michael , Walter Sarah , Gessert Devon , Sather Tamie , Jiminez Gus , Balasubramanian Archana B. , Mason Jennifer , Sim Iris , Beckett Laurel , Harvey Danielle , Donohue Michael , Jack Clifford R. , Bernstein Matthew , Fox Nick , Thompson Paul , Schuff Norbert , DeCArli Charles , Borowski Davis Bret , Gunter Jeff , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Jagust William , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Mathis Chet , Landau Susan , Morris John C. , Cairns Nigel J. , Franklin Erin , Taylor-Reinwald Lisa , Shaw Leslie M. , Trojanowki John Q. , Lee Virginia , Korecka Magdalena , Figurski Michal , Toga Arthur W. , Crawford Karen , Neu Scott , Saykin Andrew J. , Foroud Tatiana M. , Potkin Steven , Shen Li , Faber Kelley , Kim Sungeun , Nho Kwangsik , Weiner Michael W. , Thal Lean , Khachaturian Zaven , Thal Leon , Buckholtz Neil , Weiner Michael W. , Snyder Peter J. , Potter William , Paul Steven , Albert Marilyn , Frank Richard , Khachaturian Zaven , Hsiao John , Kaye Jeffrey , Quinn Joseph , Silbert Lisa , Lind Betty , Carter Raina , Dolen Sara , Schneider Lon S. , Pawluczyk Sonia , Becerra Mauricio , Teodoro Liberty , Spann Bryan M. , Brewer James , Vanderswag Helen , Fleisher Adam , Heidebrink Judith L. , Lord Joanne L. , Petersen Ronald , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Doody Rachelle S. , Villanueva-Meyer Javier , Pavlik Valory , Shibley Victoria , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Ances Beau , Morris John C. , Carroll Maria , Creech Mary L. , Franklin Erin , Mintun Mark A. , Schneider Stacy , Oliver Angela , Marson Daniel , Geldmacher David , Love Marissa Natelson , Griffith Randall , Clark David , Brockington John , Roberson Erik , Grossman Hillel , Mitsis Effie , Shah Raj C. , deToledo-Morrell Leyla , Duara Ranjan , Greig-Custo Maria T. , Barker Warren , Albert Marilyn , Onyike Chiadi , D’Agostino Daniel , Kielb Stephanie , Sadowski Martin , Sheikh Mohammed O. , Ulysse Anaztasia , Gaikwad Mrunalini , Doraiswamy P. Murali , Petrella Jeffrey R. , Borges-Neto Salvador , Wong Terence Z. , Coleman Edward , Arnold Steven E. , Karlawish Jason H. , Wolk David A. , Clark Christopher M. , Smith Charles D. , Jicha Greg , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. , Porsteinsson Anton P. , Goldstein Bonnie S. , Martin Kim , Makino Kelly M. , Ismail M. Saleem , Brand Connie , Potkin Steven G. , Preda Adrian , Nguyen Dana , Womack Kyle , Mathews Dana , Quiceno Mary , Levey Allan I. , Lah James J. , Cellar Janet S. , Burns Jeffrey M. , Swerdlow Russell H. , Brooks William M. , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H.S. , Lu Po H. , Bartzokis George , Graff-Radford Neill R , Parfitt Francine , Poki-Walker Kim , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Brosch Jared R. , Herring Scott , van Dyck Christopher H. , Carson Richard E. , MacAvoy Martha G. , Varma Pradeep , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Hsiung Ging-Yuek Robin , Mudge Benita , Sossi Vesna , Feldman Howard , Assaly Michele , Finger Elizabeth , Pasternack Stephen , Rachisky Irina , Trost Dick , Kertesz Andrew , Bernick Charles , Munic Donna , Mesulam Marek-Marsel , Rogalski Emily , Lipowski Kristine , Weintraub Sandra , Bonakdarpour Borna , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Sadowsky Carl , Villena Teresa , Turner Raymond Scott , Johnson Kathleen , Reynolds Brigid , Sperling Reisa A. , Johnson Keith A. , Marshall Gad , 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 , Tatsuoka Curtis , Fatica Parianne , Fletcher Evan , Maillard Pauline , Olichney John , DeCarli Charles , Carmichael Owen , Kittur Smita , Borrie Michael , Lee T-Y , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Potkin Steven G. , Preda Adrian , Nguyen Dana , Tariot Pierre , Burke Anna , Milliken Ann Marie , Trncic Nadira , Fleisher Adam , Reeder Stephanie , Bates Vernice , Capote Horacio , Rainka Michelle , Scharre Douglas W. , Kataki Maria , Kelley Brendan , Zimmerman Earl A. , Celmins Dzintra , Brown Alice D. , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Flashman Laura A. , Seltzer Marc , Hynes Mary L. , Santulli Robert B. , Sink Kaycee M. , Gordineer Leslie , Williamson Jeff D. , Garg Pradeep , Watkins Franklin , Ott Brian R. , Tremont Geoffrey , Daiello Lori A. , Salloway Stephen , Malloy Paul , Correia Stephen , Rosen Howard J. , Miller Bruce L. , Perry David , Mintzer Jacobo , Spicer Kenneth , Bachman David , Finger Elizabeth , Pasternak Stephen , Rachinsky Irina , Rogers John , Kertesz Andrew , Drost Dick , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Schultz Susan K. , Smith Karen Ekstam , Koleva Hristina , Nam Ki Won , Shim Hyungsub , Relkin Norman , Chiang Gloria , Lin Michael , Ravdin Lisa , Smith Amanda , Raj Balebail Ashok , Fargher Kristin 
Published: October 2016

SignificanceAlzheimer’s disease (AD) affects 10% of the elderly population. The disease remains poorly understood with no cure. The main symptom is memory loss, but other symptoms might include impaired executive function (ability to plan and accomplish goals; e.g., grocery shopping). The severity of behavioral symptoms and brain atrophy (gray matter loss) can vary widely across patients. This variability complicates diagnosis, treatment, and prevention. A mathematical model reveals distinct brain atrophy patterns, explaining variation in gray matter loss among AD dementia patients. The atrophy patterns can also explain variation in memory and executive function decline among dementia patients and at-risk nondemented participants. This model can potentially be applied to understand brain disorders with varying symptoms, including autism and schizophrenia.