{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T11:18:09Z","timestamp":1793186289225,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Whole\u2010brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington's disease (HD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden. The TrackOn\u2010HD study included 67 controls, 67 premanifest, and 10 early manifest HD (baseline and 24\u2010month data); the PADDINGTON study included 33 controls and 49 early manifest HD (baseline and 15\u2010month data). Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity from baseline to last study visit were investigated for each cohort using tract\u2010based spatial statistics. An optimized pipeline was employed to generate participant\u2010specific templates to which diffusion tensor imaging maps were registered and change maps were calculated. We examined longitudinal differences between HD expansion\u2010carriers and controls, and correlations with clinical scores, including the composite UHDRS (cUHDRS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HD expansion\u2010carriers from TrackOn\u2010HD, with lower disease burden, showed a significant longitudinal decline in FA in the left superior longitudinal fasciculus and an increase in MD across subcortical WM tracts compared to controls, while in manifest HD participants from PADDINGTON, there were significant widespread longitudinal increases in diffusivity compared to controls. Baseline scores in clinical scales including the cUHDRS predicted WM microstructural change in HD expansion\u2010carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The present study showed significant longitudinal changes in WM microstructure across the HD timecourse. Changes were evident in larger WM areas and across more metrics as the disease advanced, suggesting a progressive alteration of WM microstructure with disease evolution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2940","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T15:19:47Z","timestamp":1678807187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Progressive alterations in white matter microstructure across the timecourse of Huntington's disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6855-1093","authenticated-orcid":false,"given":"Carlos","family":"Estevez\u2010Fraga","sequence":"first","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Elmalem","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-8361","authenticated-orcid":false,"given":"Marina","family":"Papoutsi","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8921-7104","authenticated-orcid":false,"given":"Alexandra","family":"Durr","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute (ICM), AP\u2010HP, Inserm, CNRS Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin M.","family":"Rees","sequence":"additional","affiliation":[{"name":"Ixico  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Z.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymund A. C.","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Centre  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-790X","authenticated-orcid":false,"given":"Bernhard","family":"Landwehrmeyer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4532-766X","authenticated-orcid":false,"given":"Blair R.","family":"Leavitt","sequence":"additional","affiliation":[{"name":"Centre for Huntington's Disease at UBC Hospital, Department of Medical Genetics and Division of Neurology, Department of Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-4679","authenticated-orcid":false,"given":"Douglas R.","family":"Langbehn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-106X","authenticated-orcid":false,"given":"Rachael I.","family":"Scahill","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-7007","authenticated-orcid":false,"given":"Geraint","family":"Rees","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2716-2045","authenticated-orcid":false,"given":"Sarah J.","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Gregory","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2007.05.011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.07.032"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25859"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2128"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhr360"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.114.156588"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21370"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102020\u2010324377"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28489"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201053486\u20106.00056\u20109"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.10.001"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.01.022"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531\u20108249(200101)49:1<29::AID\u2010ANA7>3.0.CO;2\u2010B"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/JHD\u2010150173"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12866"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.25"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26803"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22552"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2012.12.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102014\u2010309768"},{"key":"e_1_2_10_24_1","unstructured":"Hoffman\u2010La Roche. 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