{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:28:10Z","timestamp":1786976890178,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["NU2GCK000434"],"award-info":[{"award-number":["NU2GCK000434"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Sporadic Creutzfeldt\u2010Jakob disease (sCJD) comprises multiple subtypes (MM1, MM2, MV1, MV2C, MV2K, VV1, and VV2) with distinct disease durations and spatiotemporal cascades of brain lesions. Our goal was to establish the\n                      <jats:italic>ante mortem<\/jats:italic>\n                      diagnosis of sCJD subtype, based on patient\u2010specific estimates of the spatiotemporal cascade of lesions detected by diffusion\u2010weighted magnetic resonance imaging (DWI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 488 patients with autopsy\u2010confirmed diagnosis of sCJD subtype and 50 patients with exclusion of prion disease. We applied a discriminative event\u2010based model (DEBM) to infer the spatiotemporal cascades of lesions, derived from the DWI scores of 12 brain regions assigned by three neuroradiologists. Based on the DEBM cascades and the prion protein genotype at codon 129, we developed and validated a novel algorithm for the diagnosis of the sCJD subtype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cascades of MM1, MM2, MV1, MV2C, and VV1 originated in the parietal cortex and, following subtype\u2010specific orderings of propagation, went toward the striatum, thalamus, and cerebellum; conversely, VV2 and MV2K cascades showed a striatum\u2010to\u2010cortex propagation. The proposed algorithm achieved 76.5% balanced accuracy for the sCJD subtype diagnosis, with low rater dependency (differences in accuracy of \u00b1 1% among neuroradiologists).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Ante mortem<\/jats:italic>\n                      diagnosis of sCJD subtype is feasible with this novel data\u2010driven approach, and it may be valuable for patient prognostication, stratification in targeted clinical trials, and future therapeutics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Subtype diagnosis of sporadic Creutzfeldt\u2010Jakob disease (sCJD) is achievable with diffusion MRI.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cascades of diffusion MRI abnormalities in the brain are subtype\u2010specific in sCJD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We proposed a diagnostic algorithm based on cascades of diffusion MRI abnormalities and demonstrated that it is accurate.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our method may aid early diagnosis, prognosis, stratification in clinical trials, and future therapeutics.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The present approach is applicable to other neurodegenerative diseases, enhancing the differential diagnoses.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12939","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T14:23:58Z","timestamp":1675779838000},"page":"3261-3271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A discriminative event\u2010based model for subtype diagnosis of sporadic Creutzfeldt\u2010Jakob disease using brain MRI"],"prefix":"10.1002","volume":"19","author":[{"given":"Vikram","family":"Venkatraghavan","sequence":"first","affiliation":[{"name":"Biomedical Imaging Group Rotterdam, Department of Radiology &amp; Nuclear Medicine, Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"},{"name":"Alzheimer Center Amsterdam, Neurology Vrije Universiteit, Amsterdam UMC, location VUmc  Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience Neurodegeneration  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6555-1784","authenticated-orcid":false,"given":"Riccardo","family":"Pascuzzo","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther E.","family":"Bron","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Group Rotterdam, Department of Radiology &amp; Nuclear Medicine, Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Moscatelli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Grisoli","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Pickens","sequence":"additional","affiliation":[{"name":"National Prion Disease Pathology Surveillance Center Case Western Reserve University, School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Cohen","sequence":"additional","affiliation":[{"name":"National Prion Disease Pathology Surveillance Center Case Western Reserve University, School of Medicine  Cleveland Ohio USA"},{"name":"Department of Pathology Case Western Reserve University, School of Medicine  Cleveland Ohio USA"},{"name":"Department of Neurology Case Western Reserve University University Hospitals Cleveland Medical Center  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence B.","family":"Schonberger","sequence":"additional","affiliation":[{"name":"National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gambetti","sequence":"additional","affiliation":[{"name":"Department of Pathology Case Western Reserve University, School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Appleby","sequence":"additional","affiliation":[{"name":"National Prion Disease Pathology Surveillance Center Case Western Reserve University, School of Medicine  Cleveland Ohio USA"},{"name":"Department of Pathology Case Western Reserve University, School of Medicine  Cleveland Ohio USA"},{"name":"Department of Neurology Case Western Reserve University University Hospitals Cleveland Medical Center  Cleveland Ohio USA"},{"name":"Department of Psychiatry Case Western Reserve University, University Hospitals Cleveland Medical Center  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Klein","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Group Rotterdam, Department of Radiology &amp; Nuclear Medicine, Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bizzi","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222951"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0761-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70063-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/66.1.213"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0585-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1002-8"},{"key":"e_1_2_7_9_1","first-page":"155","volume-title":"Handbook of Clinical Neurology","author":"Zerr I","year":"2018"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-00966-x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl159"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.4885"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024430"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1319"},{"key":"e_1_2_7_15_1","first-page":"1551","article-title":"Diffusion\u2010weighted and fluid\u2010attenuated inversion recovery imaging in Creutzfeldt\u2010Jakob disease: high sensitivity and specificity for diagnosis","volume":"26","author":"Young G","year":"2005","journal-title":"Am J Neuroradiol"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh575"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a96e5d"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821a4439"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005871"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02168-0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.062"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu176"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25983"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-59050-9_10"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.11.024"},{"key":"e_1_2_7_26_1","volume-title":"Applying contemporary statistical techniques","author":"Wilcox RR","year":"2003"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511802843"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7797"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1814259"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww005"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-315942"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-009-0106-8"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2019.04.019"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0308-211"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24833"}],"container-title":["Alzheimer's &amp; 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