{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:27:08Z","timestamp":1768570028471,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,2]]},"group-title":"Neurology","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Huntington\u2019s disease (HD) is a progressive neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the hungtintin gene. The disease exhibits sex-related differences in symptomatology and disease progression, but the effect on brain structural biomarkers and the interaction between sex and disease burden remain underexplored.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate the interplay between sex and disease burden on clinical measures and neuroimaging biomarkers in HD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We retrospectively analyzed data from Enroll-HD, TRACK-HD\/ON, PREDICT-HD, and IMAGE-HD studies, including a combined dataset of 19,738 participants with CAG&gt;=40. Linear mixed models were employed to evaluate the influence of sex and the sex-disease burden interaction on clinical evaluations (Unified Huntington\u2019s Disease Rating Scale and Problem Behaviors Assessment) and neuroimaging biomarkers (striatal volumes and cortical thickness), with CAG-Age Product Score (CAPS) used as a proxy for disease burden, while controlling for covariates.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Female participants exhibited less pronounced striatal atrophy and cortical thinning with increasing CAPS (caudate:\n                    <jats:italic>\n                      \u03b2\n                      <jats:sub>male\/female<\/jats:sub>\n                    <\/jats:italic>\n                    =\u20133.462\/\u20132.935, p&lt;0.05; putamen:\n                    <jats:italic>\n                      \u03b2\n                      <jats:sub>male\/female<\/jats:sub>\n                    <\/jats:italic>\n                    =\u20134.775\/\u20133.908, p&lt;0.01). Regarding clinical measures, females experience greater motor decline with increasing CAPS (Total Motor Score:\n                    <jats:italic>\n                      \u03b2\n                      <jats:sub>male\/female<\/jats:sub>\n                    <\/jats:italic>\n                    =3.024\/3.244, p&lt;0.0001), greater cognitive decline (Symbol Digit Modalities Test :\n                    <jats:italic>\n                      \u03b2\n                      <jats:sub>male\/female<\/jats:sub>\n                    <\/jats:italic>\n                    =\u201334.89\/\u201338.91, p&lt;0.0001), and greater functional decline (Total Functional Capacity:\n                    <jats:italic>\n                      \u03b2\n                      <jats:sub>male\/female<\/jats:sub>\n                    <\/jats:italic>\n                    =\u20136.449\/\u20136.817, p&lt;0.05; Independence Scale:\n                    <jats:italic>\n                      \u03b2\n                      <jats:sub>male\/female<\/jats:sub>\n                    <\/jats:italic>\n                    =\u201332.44\/\u2013 34.99, p&lt;0.001).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The sex-CAPS interaction significantly impacts both clinical and neuroimaging biomarkers of HD, underscoring the importance of incorporating sex-specific considerations into the clinical staging and management of HD.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.10.31.24315900","type":"posted-content","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T16:55:20Z","timestamp":1730566520000},"source":"Crossref","is-referenced-by-count":1,"title":["Interplay between Sex and Disease Burden in Huntington\u2019s Disease: Clinical and Neuroimaging Perspectives"],"prefix":"10.64898","author":[{"given":"Jingwen","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grayson","family":"Feng B.S.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guowen","family":"Shao M.S.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adys","family":"Mendizabal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatello","family":"Telesca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiying","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lola","family":"Ibragimova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juwairia","family":"Shoaib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie A.","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine 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