{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:26:39Z","timestamp":1768526799938,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","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":[[2022,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atrophy in the striatum is a hallmark of Huntington's disease (HD), including the period before clinical motor diagnosis (before\u2010CMD), but it extends to other subcortical structures. The study of the covariation of these structures could improve the detection of disease\u2010related longitudinal progression before\u2010CMD, provide mechanistic insights of the disease, and potentially be used to obtain accurate prospective estimates of atrophy before\u2010CMD and early after\u2010CMD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed data from 337 before\u2010CMD individuals, 236 healthy control subjects, and 95 early after\u2010CMD individuals from three studies, and we used nine subcortical regions volumes in two analyses. First, we discriminated before\u2010CMD from healthy control trajectories by integrating volume changes from these regions. Second, we estimated prospective atrophy before\u2010CMD and early after\u2010CMD by considering the influence of a region's present volume over the future volume of another one.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Before\u2010CMD progression was robustly detected across studies. Indeed, detection of before\u2010CMD progression improved when multiple structures were integrated, as opposed to analyzing the striatum alone, likely because of the reduced partial correlation between caudate and thalamic volume change before\u2010CMD. Our multivariate atrophy prediction model found a thalamus\u2013caudate association that is consistent with this pattern, which yields an improved caudate atrophy prediction in early after\u2010CMD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study is the first attempt to validate before\u2010CMD multivariate subcortical change detection across studies and to do multivariate prospective atrophy prediction in HD. These models achieve improved performance by detecting a dissociation between caudate and thalamic atrophy trajectories, and they provide a possible mechanistic understanding of the dynamics of HD. \u00a9 2022 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29219","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T08:43:24Z","timestamp":1664441004000},"page":"2407-2416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Predictive Modeling of Huntington's Disease Unfolds Thalamic and Caudate Atrophy Dissociation"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7788-9069","authenticated-orcid":false,"given":"Eduardo","family":"Castro","sequence":"first","affiliation":[{"name":"Digital Health IBM T.J. Watson Research Center  Yorktown Heights New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Polosecki","sequence":"additional","affiliation":[{"name":"Digital Health IBM T.J. Watson Research Center  Yorktown Heights New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorian","family":"Pustina","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Wood","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-9079","authenticated-orcid":false,"given":"Cristina","family":"Sampaio","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-8348","authenticated-orcid":false,"given":"Guillermo A.","family":"Cecchi","sequence":"additional","affiliation":[{"name":"Digital Health IBM T.J. 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