Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns

• DOI: 10.1038/srep43270
• Publication Date: 2017-03-09T12:32:24Z
• Authors: Jong-Yun Park; Han Kyu Na; Sungsoo Kim; Hyunwook Kim; Hee Jin Kim; Sang Won Seo; Duk L. Na; Cheol E. Han; Joon-Kyung Seong; ; Michael Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; William Jagust; John Q. Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Andrew J. Saykin; John Morris; Leslie M. Shaw; Enchi Liu; Tom Montine; Ronald G. Thomas; Michael Donohue; Sarah Walter; Devon Gessert; Tamie Sather; Gus Jiminez; Danielle Harvey; Matthew Bernstein; Nick Fox; Paul Thompson; Norbert Schuff; Charles DeCarli; Bret Borowski; Jeff Gunter; Matt Senjem; Prashanthi Vemuri; David Jones; Kejal Kantarci; Chad Ward; Robert A. Koeppe; Norm Foster; Eric M. Reiman; Kewei Chen; Chet Mathis; Susan Landau; Nigel J. Cairns; Erin Householder; Lisa Taylor Reinwald; Virginia Lee; Magdalena Korecka; Michal Figurski; Karen Crawford; Scott Neu; Tatiana M. Foroud; Steven G. Potkin; Li Shen; Faber Kelley; Sungeun Kim; Kwangsik Nho; Zaven Kachaturian; Richard Frank; Peter J. Snyder; Susan Molchan; Jeffrey Kaye; Joseph Quinn; Betty Lind; Raina Carter; Sara Dolen; Lon S. Schneider; Sonia Pawluczyk; Mauricio Beccera; Liberty Teodoro; Bryan M. Spann; James Brewer; Helen Vanderswag; Adam Fleisher; Judith L. Heidebrink; Joanne L. Lord; Sara S. Mason; Colleen S. Albers; David Knopman; Kris Johnson; Rachelle S. Doody; Javier Villanueva...; Munir Chowdhury; Susan Rountree; Mimi Dang; Yaakov Stern; Lawrence S. Honig; Karen L. Bell; Beau Ances; Maria Carroll; Sue Leon; Mark A. Mintun; Stacy Schneider; Angela Oliver; Daniel Marson; Randall Griffith; David Clark; David Geldmacher; John Brockington; Erik Roberson; Hillel Grossman; Effie Mitsis; Leyla de Toledo-M...; Raj C. Shah; Ranjan Duara; Daniel Varon; Maria T. Greig; Peggy Roberts; Marilyn Albert; Chiadi Onyike; Daniel D’Agostino II; Stephanie Kielb; James E. Galvin; Dana M. Pogorelec; Brittany Cerbone; Christina A. Michel; Henry Rusinek; Mony J. de Leon; Lidia Glodzik; Susan De Santi; P. Murali Doraiswamy; Jeffrey R. Petrella; Terence Z. Wong; Steven E. Arnold; Jason H. Karlawish; David Wolk; Charles D. Smith; Greg Jicha; Peter Hardy; Partha Sinha; Elizabeth Oates; Gary Conrad; Oscar L. Lopez; MaryAnn Oakley; Donna M. Simpson; Anton P. Porstein...; Bonnie S. Goldstein; Kim Martin; Kelly M. Makino; M. Saleem Ismail; Connie Brand; Ruth A. Mulnard; Gaby Thai; Catherine Mc Adam...; Kyle Womack; Dana Mathews; Mary Quiceno; Ramon Diaz Arrastia; Richard King; Myron Weiner; Kristen Martin Cook; Michael DeVous; Allan I. Levey; James J. Lah; Janet S. Cellar; Jeffrey M. Burns; Heather S. Anderson; Russell H. Swerdlow; Liana Apostolova; Kathleen Tingus; Ellen Woo; Daniel H. S. Silv...; Po H. Lu; George Bartzokis; Neill R. Graff Ra...; Francine Parfitt; Tracy Kendall; Heather Johnson; Martin R. Farlow; Ann Marie Hake; Brandy R. Matthews; Scott Herring; Cynthia Hunt; Christopher H. va...; Richard E. Carson; Martha G. MacAvoy; Howard Chertkow; Howard Bergman; Chris Hosein; Sandra Black; Bojana Stefanovic; Curtis Caldwell; Ging Yuek Robin H...; Howard Feldman; Benita Mudge; Michele Assaly; Dick Trost; Charles Bernick; Donna Munic; Diana Kerwin; Marek Marsel Mesulam; Kristine Lipowski; Chuang Kuo Wu; Nancy Johnson; Carl Sadowsky; Walter Martinez; Teresa Villena; Raymond Scott Turner; Kathleen Johnson; Brigid Reynolds; Reisa A. Sperling; Keith A. Johnson; Gad Marshall; Meghan Frey; Jerome Yesavage; Joy L. Taylor; Barton Lane; Allyson Rosen; Jared Tinklenberg; Marwan N. Sabbagh; Christine M. Belden; Sandra A. Jacobson; Sherye A. Sirrel; Neil Kowall; Ronald Killiany; Andrew E. Budson; Alexander Norbash; Patricia Lynn Joh...; Thomas O. Obisesan; Saba Wolday; Joanne Allard; Alan Lerner; Paula Ogrocki; Leon Hudson; Evan Fletcher; Owen Carmichael; John Olichney; Smita Kittur; Michael Borrie; T. Y. Lee; Rob Bartha; Sterling Johnson; Sanjay Asthana; Cynthia M. Carlsson; Adrian Preda; Dana Nguyen; Pierre Tariot; Stephanie Reeder; Vernice Bates; Horacio Capote; Michelle Rainka; Douglas W. Scharre; Maria Kataki; Anahita Adeli; 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; Jeff D. Williamson; Pradeep Garg; Franklin Watkins; Brian R. Ott; Henry Querfurth; Geoffrey Tremont; Stephen Salloway; Paul Malloy; Stephen Correia; Howard J. Rosen; Bruce L. Miller; Jacobo Mintzer; Kenneth Spicer; David Bachman; Elizabether Finger; Stephen Pasternak; Irina Rachinsky; John Rogers; Andrew Kertesz; Nunzio Pomara; Raymundo Hernando; Antero Sarrael; Susan K. Schultz; Laura L. Boles Ponto; Hyungsub Shim; Karen Elizabeth S...; Norman Relkin; Gloria Chaing; Lisa Raudin; Amanda Smith; Kristin Fargher; Balebail Ashok Raj
• Keywords: Male; Aging; Atrophy / pathology*; Biological Psychology; 610; Neurodegenerative; Alzheimer's Disease; Article; 03 medical and health sciences; 0302 clinical medicine; Alzheimer Disease; 616; Acquired Cognitive Impairment; Psychology; 2.1 Biological and endogenous factors; Humans; Alzheimer Disease / pathology*; Atrophy / diagnostic imaging; Aged; Cerebral Cortex; Alzheimer Disease / classification*; Cerebral Cortex / pathology*; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Alzheimer’s Disease Neuroimaging Initiative; Middle Aged; Magnetic Resonance Imaging; Brain Disorders; 4.1 Discovery and preclinical testing of markers and technologies; Cerebral Cortex / diagnostic imaging; Neurological; Dementia; Female; Atrophy; Alzheimer Disease / diagnostic imaging

AbstractAccumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.