{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:54:52Z","timestamp":1787504092925,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite advancements in understanding Huntington's disease (HD) over the past two decades, absence of disease\u2010modifying treatments remains a challenge. Accurately characterizing progression states is crucial for developing effective therapeutic interventions. Various factors contribute to this challenge, including the need for precise methods that can account for the complex nature of HD progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to address this gap by leveraging the concept of the brain's biological age as a foundation for a data\u2010driven clustering method to delineate various states of progression. Brain\u2010predicted age, influenced by somatic expansion and its impact on brain volumes, offers a promising avenue for stratification by stratifying subgroups and determining the optimal timing for interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To achieve this, data from 953 participants across diverse cohorts, including PREDICT\u2010HD, TRACK\u2010HD, and IMAGE\u2010HD, were meticulously analyzed. Brain\u2010predicted age was computed using sophisticated algorithms, and participants were categorized into four groups based on CAG and age product score. Unsupervised k\u2010means clustering with brain\u2010predicted age difference (brain\u2010PAD) was then employed to identify distinct progression states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis revealed significant disparities in brain\u2010predicted age between HD participants and controls, with these differences becoming more pronounced as the disease progressed. Brain\u2010PAD demonstrated a correlation with disease severity, effectively identifying five distinct progression states characterized by significant longitudinal disparities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings highlight the potential of brain\u2010PAD in capturing HD progression states, thereby enhancing prognostic methodologies and providing valuable insights for future clinical trial designs and interventions. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30109","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T02:04:37Z","timestamp":1738116277000},"page":"627-641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Brain Age as a New Measure of Disease Stratification in Huntington's Disease"],"prefix":"10.1002","volume":"40","author":[{"given":"Pubu M.","family":"Abeyasinghe","sequence":"first","affiliation":[{"name":"School of Psychological Sciences and Turner Institute for Brain and Mental Health Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Cole","sequence":"additional","affiliation":[{"name":"Centre for Medical Image Computing, Department of Computer Science University College London  London United Kingdom"},{"name":"Dementia Research Centre, Institute of Neurology University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeel","family":"Razi","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences and Turner Institute for Brain and Mental Health Monash University  Melbourne Victoria Australia"},{"name":"Monash Biomedical Imaging Monash University  Clayton Victoria Australia"},{"name":"Welcome Centre for Human Neuroimaging, UCL  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govinda R.","family":"Poudel","sequence":"additional","affiliation":[{"name":"Mary MacKillop Institute for Health Research, Australian Catholic University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane S.","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-7169","authenticated-orcid":false,"given":"Sarah J.","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"UCL Huntington's Disease Centre, UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Carver College of Medicine, The University of Iowa  Iowa City Iowa USA"},{"name":"Department of Biostatistics College of Public Health, The University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-6760","authenticated-orcid":false,"given":"Nellie","family":"Georgiou\u2010Karistianis","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences and Turner Institute for Brain and Mental Health Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-40"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00120-X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.128728"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00078"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70088-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70263-0"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.08.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.12.009"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.114.156588"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305114"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074131"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22601"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","unstructured":"AbeyasinghePM LongJD RaziA PustinaD PaulsenJS TabriziSJ Georgiou\u2010KaristianisN.Tracking Huntington's disease progression using motor functional cognitive and imaging markers;2021. Movement Disorders.","DOI":"10.1002\/mds.28650"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25709"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1323"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.10.095"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.01.005"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00789"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2413"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24367"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25746"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.103175"},{"key":"e_1_2_9_25_1","volume-title":"SPM12 Manual","author":"Ashburner J","year":"2014"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v011.i09"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.07.059"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26502"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9868.00353"},{"key":"e_1_2_9_30_1","first-page":"1","article-title":"Applying the Huntington's disease integrated staging system (HD\u2010ISS) to observational studies","author":"Long JD","year":"2023","journal-title":"J Huntington's Dis"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2013.00012"},{"key":"e_1_2_9_32_1","article-title":"Deep learning in psychiatry and neurology: why now and where to begin","volume":"220","author":"Varatharajah Y","year":"2020","journal-title":"Neuroimage"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.03.014"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.30109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:32:40Z","timestamp":1760952760000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.30109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/mds.30109"],"URL":"https:\/\/doi.org\/10.1002\/mds.30109","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]},"assertion":[{"value":"2024-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}