{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T16:34:24Z","timestamp":1793982864509,"version":"4.8.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009408","name":"Fondation Brain Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009408","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["CFI Project 34874"],"award-info":[{"award-number":["CFI Project 34874"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000008","name":"Health Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009408","name":"Fondation Brain Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Frontotemporal dementia in genetic forms is highly heterogeneous and begins many years to prior symptom onset, complicating disease understanding and treatment development. Unifying methods to stage the disease during both the presymptomatic and symptomatic phases are needed for the development of clinical trials outcomes. Here we used the contrastive trajectory inference (cTI), an unsupervised machine learning algorithm that analyzes temporal patterns in high\u2010dimensional large\u2010scale population datasets to obtain individual scores of disease stage. We used cross\u2010sectional MRI data (gray matter density, T1\/T2 ratio as a proxy for myelin content, resting\u2010state functional amplitude, gray matter fractional anisotropy, and mean diffusivity) from 383 gene carriers (269 presymptomatic and 115 symptomatic) and a control group of 253 noncarriers in the Genetic Frontotemporal Dementia Initiative. We compared the cTI\u2010obtained disease scores to the estimated years to onset (age\u2014mean age of onset in relatives), clinical, and neuropsychological test scores. The cTI based disease scores were correlated with all clinical and neuropsychological tests (measuring behavioral symptoms, attention, memory, language, and executive functions), with the highest contribution coming from mean diffusivity. Mean cTI scores were higher in the presymptomatic carriers than controls, indicating that the method may capture subtle pre\u2010dementia cerebral changes, although this change was not replicated in a subset of subjects with complete data. This study provides a proof of concept that cTI can identify data\u2010driven disease stages in a heterogeneous sample combining different mutations and disease stages of genetic FTD using only MRI metrics.<\/jats:p>","DOI":"10.1002\/hbm.25727","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T07:38:21Z","timestamp":1643960301000},"page":"1821-1835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Data\u2010driven staging of genetic frontotemporal dementia using multi\u2010modal <scp>MRI<\/scp>"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-0023","authenticated-orcid":false,"given":"Jillian","family":"McCarthy","sequence":"first","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-9814","authenticated-orcid":false,"given":"Barbara","family":"Borroni","sequence":"additional","affiliation":[{"name":"Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Sanchez\u2010Valle","sequence":"additional","affiliation":[{"name":"Alzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic, Institut d'Investigaci\u00f3ns Biom\u00e8diques August Pi I Sunyer University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fermin","family":"Moreno","sequence":"additional","affiliation":[{"name":"Cognitive Disorders Unit, Department of Neurology Donostia University Hospital  San Sebastian Gipuzkoa Spain"},{"name":"Neuroscience Area Biodonostia Health Research Institute  San Sebastian Gipuzkoa Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert","family":"Laforce","sequence":"additional","affiliation":[{"name":"Clinique Interdisciplinaire de M\u00e9moire, D\u00e9partement des Sciences Neurologiques, CHU de Qu\u00e9bec, and Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Quebec Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Graff","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine Karolinska University Hospital\u2010Huddinge  Stockholm Sweden"},{"name":"Unit for Hereditary Dementias Theme Aging, Karolinska University Hospital  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthis","family":"Synofzik","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, Hertie\u2010Institute for Clinical Brain Research and Center of Neurology University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Center for Neurodegenerative Diseases (DZNE)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Neurodegenerative Diseases Unit  Milan Italy"},{"name":"Department of Biomedical, Surgical, and Dental Sciences University of Milan, Dino Ferrari Center  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Rowe","sequence":"additional","affiliation":[{"name":"University of Cambridge Department of Clinical Neurosciences Cambridge University Hospitals NHS Trust, and RC Cognition and Brain Sciences Unit  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre, Sunnybrook Research Institute University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Toronto Western Hospital Tanz Centre for Research in Neurodegenerative Disease  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Finger","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurological Sciences University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences KU Leuven  Leuven Belgium"},{"name":"Neurology Service University Hospitals Leuven  Belgium"},{"name":"Leuven Brain Institute KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"de Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Tagliavini","sequence":"additional","affiliation":[{"name":"Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Santana","sequence":"additional","affiliation":[{"name":"Neurology Department Centro Hospitalar e Universit\u00e1rio de Coimbra  Coimbra Portugal"},{"name":"Center for Neuroscience and Cell Biology, Faculty of Medicine University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology University of Oxford  Oxford UK"},{"name":"Department of Brain Sciences Imperial College London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Gerhard","sequence":"additional","affiliation":[{"name":"Division of Neuroscience &amp; Experimental Psychology, Faculty of Medicine, Biology, and Health University of Manchester  Manchester UK"},{"name":"Departments of Geriatric Medicine and Nuclear Medicine Essen University Hospital  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Danek","sequence":"additional","affiliation":[{"name":"Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[{"name":"Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  Munich Germany"},{"name":"Munich Cluster of Systems Neurology (SyNergy)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Frisoni","sequence":"additional","affiliation":[{"name":"LANE \u2010 Laboratory of Alzheimer's Neuroimaging and Epidemiology IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli  Brescia Italy"},{"name":"Memory Clinic and LANVIE\u2010Laboratory of Neuroimaging of Aging University Hospitals and University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Ghidoni","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Sorbi","sequence":"additional","affiliation":[{"name":"Department of Neurofarba University of Florence  Italy"},{"name":"IRCCS Fondazione Don Carlo Gnocchi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lize C.","family":"Jiskoot","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus University Medical Centre  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harro","family":"Seelaar","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus University Medical Centre  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"van Swieten","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus University Medical Centre  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Rohrer","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Dementia Research Centre UCL Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser","family":"Iturria\u2010Medina","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"},{"name":"Neurology and Neurosurgery Department, Montreal Neurological Institute McGill University  Montreal Quebec Canada"},{"name":"Ludmer Centre for Neuroinformatics &amp; Mental Health McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Ducharme","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre, Montreal Neurological Institute McGill University  Montreal Quebec Canada"},{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"GENetic Frontotemporal Dementia Initiative (GENFI)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04608-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.07.007"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323487"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12902"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.10.008"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000583"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.07.014"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2016.03.019"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.11.024"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.08.047"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821103e6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02133-x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.02.058"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz400"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.601"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy288"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00171"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22420"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12250"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.12.006"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.325"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.75"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30394-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.08.196"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000338176"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.12.017"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323541"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150340"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.117"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr179"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70324-2"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003154"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.024"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.04.007"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116137"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13640"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30354-0"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d9edde"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05892-0"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.04.012"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25727","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hbm.25727","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T03:41:21Z","timestamp":1693107681000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.25727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,4,15]]}},"alternative-id":["10.1002\/hbm.25727"],"URL":"https:\/\/doi.org\/10.1002\/hbm.25727","archive":["Portico"],"relation":{},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"value":"1065-9471","type":"print"},{"value":"1097-0193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"assertion":[{"value":"2021-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}