AUTHOR=Gupta Yubraj , Lama Ramesh Kumar , Kwon Goo-Rak ,  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 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 , Natelson Love Marissa , 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. , Anaztasia Ulysse , Mrunalini Gaikwad , 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. , Leslie Gordineer , 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 , Weiner Michael W. , Aisen Paul , Weiner Michael , Aisen Paul , Petersen Ronald , Green Robert C. , Harvey Danielle , Jack Clifford R. , Jagust William , Morris John C. , Saykin Andrew J. , Shaw Leslie M. , Toga Arthur W. , Trojanowki John Q. , Neylan Thomas , Grafman Jordan , Green Robert C. , Montine Tom , Weiner Michael , Petersen Ronald , Aisen Paul , Thomas Ronald G. , Donohue Michael , Devon Gessert , Sather Tamie , Melissa Davis , Morrison Rosemary , Jiminez Gus , Neylan Thomas , Jacqueline Hayes , Shannon Finley , Harvey Danielle , Donohue Michael , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , Senjem Matt , Kejal Kantarci , Chad Ward , Jagust William , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Landau Susan , Morris John C. , Cairns Nigel J. , Householder Erin , Shaw Leslie M. , Trojanowki John Q. , Lee Virginia , Korecka Magdalena , Figurski Michal , Toga Arthur W. , Karen Crawford , Scott Neu , Saykin Andrew J. , Foroud Tatiana M. , Potkin Steven , Shen Li , Faber Kelley , Kim Sungeun , Nho Kwangsik , Weiner Michael W. , Karl Friedl , Schneider Lon S. , Pawluczyk Sonia , Mauricio Becerra , Brewer James , Vanderswag Helen , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Fleischman Debra , Arfanakis Konstantinos , Shah Raj C. , Duara Ranjan , Varon Daniel , Greig Maria T , Doraiswamy P. Murali , Petrella Jeffrey R. , James Olga , Porsteinsson Anton P. , Goldstein Bonnie , Martin Kimberly S. , Potkin Steven G. , Preda Adrian , Nguyen Dana , Mintzer Jacobo , Massoglia Dino , Brawman-Mintzer Olga , Sadowsky Carl , Martinez Walter , Villena Teresa , Jagust William , Landau Susan , Rosen Howard , Perry David , Turner Raymond Scott , Behan Kelly , Reynolds Brigid , Sperling Reisa A. , Johnson Keith A. , Marshall Gad , Sabbagh Marwan N. , Jacobson Sandra A. , Sirrel Sherye A. , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Johnson Sterling C. , Fruehling J. Jay , Harding Sandra , Peskind Elaine R. , Petrie Eric C. , Li Gail , Yesavage Jerome A. , Taylor Joy L. , Furst Ansgar J. , Chao Steven , Relkin Norman , Chiang Gloria , Ravdin Lisa , Ravdin Lisa , Mackin Scott , Aisen Paul , Raman Rema , Mackin Scott , Weiner Michael , Aisen Paul , Raman Rema , Jack Clifford R. , Landau Susan , Saykin Andrew J. , Toga Arthur W. , DeCarli Charles , Koeppe Robert A. , Green Robert C. , Drake Erin , Weiner Michael , Aisen Paul , Raman Rema , Donohue Mike , Jimenez Gustavo , Gessert Devon , Harless Kelly , Salazar Jennifer , Cabrera Yuliana , Walter Sarah , Hergesheimer Lindsey , Shaffer Elizabeth , Mackin Scott , Nelson Craig , Bickford David , Butters Meryl , Zmuda Michelle , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , Senjem Matt , Kantarci Kejal , Ward Chad , Reyes Denise , Koeppe Robert A. , Landau Susan , Toga Arthur W. , Crawford Karen , Neu Scott , Saykin Andrew J. , Foroud Tatiana M. , Faber Kelley M. , Nho Kwangsik , Nudelman Kelly N. , Mackin Scott , Rosen Howard , Nelson Craig , Bickford David , Au Yiu Ho , Scherer Kelly , Catalinotto Daniel , Stark Samuel , Ong Elise , Fernandez Dariella , Butters Meryl , Zmuda Michelle , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. 

TITLE=Prediction and Classification of Alzheimer’s Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers

JOURNAL=Frontiers in Computational Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2019.00072

DOI=10.3389/fncom.2019.00072

ISSN=1662-5188

ABSTRACT=<p>Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.</p>