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Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion\u2010weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre\u2010HD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>As part of the PREDICT\u2010HD study,<jats:italic>N<\/jats:italic>\u2009=\u2009191 pre\u2010HD individuals and 70 healthy controls underwent two or more (baseline and 1\u20135 year follow\u2010up) DWI, with<jats:italic>n<\/jats:italic>\u2009=\u2009649 total sessions. Images were processed using cutting\u2010edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato\u2010sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre\u2010HD participants were divided into three CAG\u2010Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cross\u2010sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the largest longitudinal DWI study of pre\u2010HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD.<jats:italic>Hum Brain Mapp 38:1460\u20131477, 2017<\/jats:italic>. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hbm.23465","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T10:16:56Z","timestamp":1483438616000},"page":"1460-1477","source":"Crossref","is-referenced-by-count":47,"title":["Longitudinal diffusion changes in prodromal and early<scp>HD<\/scp>: Evidence of white\u2010matter tract deterioration"],"prefix":"10.1002","volume":"38","author":[{"given":"Joseph J.","family":"Shaffer","sequence":"first","affiliation":[{"name":"Department of Radiology University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Ghayoor","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Iowa City Iowa"},{"name":"Department of Biostatistics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina Eun\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Lourens","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren J.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Department of Radiology Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl\u2010Fredrik","family":"Westin","sequence":"additional","affiliation":[{"name":"Department of Radiology Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Rathi","sequence":"additional","affiliation":[{"name":"Department of Radiology Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Magnotta","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Iowa Iowa City Iowa"},{"name":"Department of Psychiatry University of Iowa Iowa City Iowa"},{"name":"Biomedical Engineering University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane S.","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Iowa City Iowa"},{"name":"Department of Neurology, Carver College of Medicine University of Iowa Iowa City Iowa"},{"name":"Neuroscience, Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering University of Iowa Iowa City Iowa"},{"name":"Department of Psychiatry University of Iowa Iowa City Iowa"},{"name":"Biomedical Engineering University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,3]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"AvantsBB TustisonNJ SongG GeeJC(2009): ANTS: Open\u2010Source Tools for Normalization And Neuroanatomy. 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