{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:38:37Z","timestamp":1789983517449,"version":"4.0.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T00:00:00Z","timestamp":1483401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007333","name":"Alzheimer\u2019s Disease Neuroimaging Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007136","name":"Secretar\u00eda de Estado de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["TEC2014-60337-R"],"award-info":[{"award-number":["TEC2014-60337-R"]}],"id":[{"id":"10.13039\/501100007136","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007136","name":"Secretar\u00eda de Estado de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PSI2013-47724-P"],"award-info":[{"award-number":["PSI2013-47724-P"]}],"id":[{"id":"10.13039\/501100007136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0168011","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T15:40:00Z","timestamp":1483976400000},"page":"e0168011","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Early Prediction of Alzheimer\u2019s Disease Using Null Longitudinal Model-Based Classifiers"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5743-1800","authenticated-orcid":true,"given":"Giovana","family":"Gavidia-Bovadilla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Kanaan-Izquierdo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Matar\u00f3-Serrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Perera-Lluna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,1,3]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"CR Jack","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref2","article-title":"Preclinical Alzheimer\u2019s disease: Definition, natural history, and diagnostic criteria","author":"B Dubois","year":"2016","journal-title":"Preclinical Alzheimer\u2019s disease: Definition, natural history, and diagnostic criteria"},{"issue":"3","key":"ref3","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.neuroimage.2007.09.073","article-title":"Alzheimer\u2019s disease diagnosis in individual subjects using structural MR images: validation studies","volume":"39","author":"P Vemuri","year":"2008","journal-title":"Neuroimage"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrneurol.2009.215","article-title":"The clinical use of structural MRI in Alzheimer disease","volume":"6","author":"GB Frisoni","year":"2010","journal-title":"Nature reviews Neurology"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jalz.2010.03.013","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans","volume":"6","author":"AJ Saykin","year":"2010","journal-title":"Alzheimer\u2019s & dementia: the journal of the Alzheimer\u2019s Association"},{"issue":"48","key":"ref6","doi-asserted-by":"crossref","first-page":"15223","DOI":"10.1523\/JNEUROSCI.3252-09.2009","article-title":"One-year brain atrophy evident in healthy aging","volume":"29","author":"AM Fjell","year":"2009","journal-title":"J Neurosci"},{"issue":"964","key":"ref7","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1136\/pgmj.2005.036665","article-title":"Ageing and the brain","volume":"82","author":"R Peters","year":"2006","journal-title":"Postgraduate medical journal"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1093\/cercor\/bhh032","article-title":"Thinning of the cerebral cortex in aging","volume":"14","author":"D Salat","year":"2004","journal-title":"Cerebral Cortex"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.neuroimage.2013.08.022","article-title":"A longitudinal study of brain atrophy over two years in community-dwelling older individuals","volume":"86","author":"J Jiang","year":"2014","journal-title":"Neuroimage"},{"issue":"9","key":"ref10","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00234-012-1005-0","article-title":"Education increases reserve against Alzheimer\u2019s disease-evidence from structural MRI analysis","volume":"54","author":"Y Liu","year":"2012","journal-title":"Neuroradiology"},{"key":"ref11","first-page":"135","article-title":"Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer\u2019s disease","volume":"2","author":"GP Morris","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"796024","DOI":"10.6064\/2012\/796024","article-title":"The role of tau in neurodegenerative diseases and its potential as a therapeutic target","volume":"2012","author":"MS Wolfe","year":"2012","journal-title":"Scientifica"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1212\/WNL.43.11.2412-a","article-title":"The Clinical Dementia Rating (CDR): current version and scoring rules","volume":"43","author":"J Morris","year":"1993","journal-title":"Neurology"},{"issue":"3","key":"ref14","first-page":"189","article-title":"Mini-mental state. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"M Folstein","year":"1975","journal-title":"Journal of Psychiatric Research"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jalz.2005.06.003","article-title":"Ways toward an early diagnosis in Alzheimer\u2019s disease: the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","volume":"1","author":"SG Mueller","year":"2005","journal-title":"Alzheimers Dement"},{"issue":"4","key":"ref16","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.nic.2005.09.008","article-title":"The Alzheimer\u2019s disease neuroimaging initiative","volume":"15","author":"SG Mueller","year":"2005","journal-title":"Neuroimaging Clin N Am"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"MS Albert","year":"2011","journal-title":"Alzheimers Dement"},{"issue":"4","key":"ref18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ana.21610","article-title":"Cerebrospinal fluid biomarker signature in Alzheimer\u2019s disease neuroimaging initiative subjects","volume":"65","author":"LM Shaw","year":"2009","journal-title":"Ann Neurol"},{"issue":"7","key":"ref19","doi-asserted-by":"crossref","first-page":"e21896","DOI":"10.1371\/journal.pone.0021896","article-title":"Identification of conversion from mild cognitive impairment to Alzheimer\u2019s disease using multivariate predictors","volume":"6","author":"Y Cui","year":"2011","journal-title":"PLoS One"},{"issue":"3","key":"ref20","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.neuroimage.2010.01.005","article-title":"Estimating the age of healthy subjects from T1-weighted MRI scans using kernel methods: exploring the influence of various parameters","volume":"50","author":"K Franke","year":"2010","journal-title":"Neuroimage"},{"issue":"4","key":"ref21","first-page":"235","article-title":"Longitudinal changes in individual BrainAGE in healthy aging, mild cognitive impairment, and Alzheimer\u2019s disease","volume":"25","author":"K Franke","year":"2012","journal-title":"Journal of Gerontopsychology and Geriatric Psychiatry"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0067346","article-title":"BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer\u2019s Disease","volume":"8","author":"C Gaser","year":"2013","journal-title":"PLoS ONE"},{"issue":"4","key":"ref23","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/joim.12028","article-title":"An MRI-based index to measure the severity of Alzheimer\u2019s disease-like structural pattern in subjects with mild cognitive impairment","volume":"273","author":"G Spulber","year":"2013","journal-title":"Journal of internal medicine"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fnagi.2014.00145","article-title":"Application of a MRI based index to longitudinal atrophy change in Alzheimer disease, mild cognitive impairment and healthy older individuals in the AddNeuroMed cohort","volume":"6","author":"C Aguilar","year":"2014","journal-title":"Frontiers in aging neuroscience"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.neuroimage.2011.09.069","article-title":"Multi-Modal Multi-Task Learning for Joint Prediction of Multiple Regression and Classification Variables in Alzheimer\u2019s Disease","volume":"59","author":"D Zhang","year":"2012","journal-title":"Neuroimage"},{"key":"ref26","first-page":"275","article-title":"Medical Image Computing and Computer-Assisted Intervention\u2013MICCAI 2013","author":"B Jie","year":"2013"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.neuroimage.2013.09.015","article-title":"Inter-modality relationship constrained multi-modality multi-task feature selection for Alzheimer\u2019s Disease and mild cognitive impairment identification","volume":"84","author":"F Liu","year":"2014","journal-title":"NeuroImage"},{"issue":"2","key":"ref28","first-page":"583","article-title":"Deep Learning-Based Feature Representation for AD\/MCI Classification","volume":"16","author":"HI Suk","year":"2013","journal-title":"Med Image Comput Comput Assist Interv"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.neuroimage.2014.06.077","article-title":"Hierarchical feature representation and multimodal fusion with deep learning for AD\/MCI diagnosis","volume":"101","author":"HI Suk","year":"2014","journal-title":"NeuroImage"},{"issue":"Pt 3","key":"ref30","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/brain\/awm319","article-title":"Automatic classification of MR scans in Alzheimer\u2019s disease","volume":"131","author":"S Kl\u00f6ppel","year":"2008","journal-title":"Brain"},{"issue":"2","key":"ref31","first-page":"766","article-title":"Automatic classification of patients with Alzheimer\u2019s disease from structural MRI: A comparison of ten methods using the ADNI database","volume":"56","author":"R Cuingnet","year":"2011","journal-title":"Multivariate Decoding and Brain Reading"},{"issue":"3","key":"ref32","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","volume":"74","author":"RC Petersen","year":"2010","journal-title":"Neurology"},{"issue":"19","key":"ref33","doi-asserted-by":"crossref","first-page":"8237","DOI":"10.1523\/JNEUROSCI.5506-12.2013","article-title":"Brain changes in older adults at very low risk for Alzheimer\u2019s disease","volume":"33","author":"AM Fjell","year":"2013","journal-title":"J Neurosci"},{"issue":"8","key":"ref34","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1093\/brain\/awp123","article-title":"Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer\u2019s disease","volume":"132","author":"R Desikan","year":"2009","journal-title":"Brain"},{"issue":"8","key":"ref35","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.neurobiolaging.2010.04.023","article-title":"Automated MRI measures predict progression to Alzheimer\u2019s disease","volume":"31","author":"RS Desikan","year":"2010","journal-title":"Neurobiol Aging"},{"issue":"1, Supplement","key":"ref36","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jalz.2011.09.172","article-title":"The Alzheimer\u2019s Disease Neuroimaging Initiative: A review of papers published since its inception","volume":"8","author":"MW Weiner","year":"2012","journal-title":"Alzheimer\u2019s and Dementia"},{"issue":"4","key":"ref37","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/jmri.21049","article-title":"The Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI): MRI methods","volume":"27","author":"C Jack","year":"2008","journal-title":"J Magn Reson Imaging"},{"issue":"3","key":"ref38","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/cercor\/bhn113","article-title":"The cortical signature of Alzheimer\u2019s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals","volume":"19","author":"BC Dickerson","year":"2009","journal-title":"Cereb Cortex"},{"issue":"3","key":"ref39","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1016\/j.neuroimage.2011.09.085","article-title":"Individual subject classification for Alzheimer\u2019s disease based on incremental learning using a spatial frequency representation of cortical thickness data","volume":"59","author":"Y Cho","year":"2012","journal-title":"Neuroimage"},{"issue":"3","key":"ref40","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"R Desikan","year":"2006","journal-title":"NeuroImage"},{"key":"ref41","article-title":"FreeSurfer","author":"B Fischl","year":"2012","journal-title":"Neuroimage"},{"issue":"8","key":"ref42","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.neurobiolaging.2010.04.030","article-title":"Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study","volume":"31","author":"D Tosun","year":"2010","journal-title":"Neurobiol Aging"},{"issue":"1","key":"ref43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"D Bates","year":"2015","journal-title":"Journal of Statistical Software"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/cem.1180020306","article-title":"PLS regression methods","volume":"2","author":"A H\u00f6skuldsson","year":"1988","journal-title":"Journal of Chemometrics"},{"issue":"2","key":"ref45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0169-7439(01)00155-1","article-title":"PLS-regression: a basic tool of chemometrics","volume":"58","author":"S Wold","year":"2001","journal-title":"Chemometrics and Intelligent Laboratory Systems"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/(SICI)1099-128X(199701)11:1<73::AID-CEM435>3.0.CO;2-#","article-title":"Improved PLS algorithms","volume":"11","author":"BS Dayal","year":"1997","journal-title":"Journal of Chemometrics"},{"key":"ref47","article-title":"pls: Partial Least Squares and Principal Component regression; 2013","author":"BH Mevik"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1001\/archneur.55.2.169","article-title":"Sex differences in brain aging: a quantitative magnetic resonance imaging study","volume":"55","author":"CE Coffey","year":"1998","journal-title":"Arch Neurol"},{"issue":"1","key":"ref49","first-page":"112","article-title":"Gender effects on age-related changes in brain structure","volume":"21","author":"J Xu","year":"2000","journal-title":"AJNR Am J Neuroradiol"},{"key":"ref50","first-page":"1","article-title":"Male brain ages faster: the age and gender dependence of subcortical volumes","author":"A Kir\u00e1ly","year":"2015","journal-title":"Brain Imaging and Behavior"},{"issue":"5","key":"ref51","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00401-013-1151-4","article-title":"Longitudinal change in CSF Tau and ABeta biomarkers for up to 48 months in ADNI","volume":"126","author":"JB Toledo","year":"2013","journal-title":"Acta Neuropathologica"},{"issue":"8","key":"ref52","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1001\/archneurol.2010.179","article-title":"Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people","volume":"67","author":"G De Meyer","year":"2010","journal-title":"Arch Neurol"},{"issue":"6","key":"ref53","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/hipo.20626","article-title":"Fully automatic hippocampus segmentation and classification in Alzheimer\u2019s disease and mild cognitive impairment applied on data from ADNI","volume":"19","author":"M Chupin","year":"2009","journal-title":"Hippocampus"},{"issue":"2","key":"ref54","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.neuroimage.2012.01.098","article-title":"Measuring longitudinal change in the hippocampal formation from in vivo high-resolution T2-weighted MRI","volume":"60","author":"SR Das","year":"2012","journal-title":"Neuroimage"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0168011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T09:16:08Z","timestamp":1540199768000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0168011"}},"subtitle":[],"editor":[{"given":"Kewei","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,1,3]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,1,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0168011","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,3]]}}}