{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:13:06Z","timestamp":1789261986950,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS052318"],"award-info":[{"award-number":["R01 NS052318"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 NS082168"],"award-info":[{"award-number":["T32 NS082168"]}],"id":[{"id":"10.13039\/100000002","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":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rasagiline has received attention as a potential disease\u2010modifying therapy for Parkinson's disease (PD). Whether rasagiline is disease modifying remains in question.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The main objective of this study was to determine whether rasagiline has disease\u2010modifying effects in PD over 1 year. Secondarily we evaluated two diffusion magnetic resonance imaging pulse sequences to determine the best sequence to measure disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective, randomized, double\u2010blind, placebo\u2010controlled trial assessed the effects of rasagiline administered at 1\u2009mg\/day over 12\u2009months in early\u2010stage PD. The primary outcome was 1\u2010year change in free\u2010water accumulation in posterior substantia nigra (pSN) measured using two diffusion magnetic resonance imaging pulse sequences, one with a repetition time (TR) of 2500\u2009ms (short TR; n\u00a0=\u00a090) and one with a TR of 6400\u2009ms (long TR; n\u00a0=\u00a075). Secondary clinical outcomes also were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Absolute change in pSN free\u2010water accumulation was not significantly different between groups (short TR: <jats:italic>P<\/jats:italic>\u2009=\u20090.346; long TR: <jats:italic>P<\/jats:italic>\u2009=\u20090.228). No significant differences were found in any secondary clinical outcomes between groups. Long TR, but not short TR, data show pSN free\u2010water increased significantly over 1 year (<jats:italic>P<\/jats:italic>\u2009=\u20090.025). Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III increased significantly over 1 year (<jats:italic>P<\/jats:italic>\u2009=\u20090.009), and baseline free\u2010water in the pSN correlated with the 1\u2010year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III (<jats:italic>P<\/jats:italic>\u2009=\u20090.004) and 1\u2010year change in bradykinesia score (<jats:italic>P<\/jats:italic>\u2009=\u20090.044).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We found no evidence that 1\u2009mg\/day rasagiline has a disease\u2010modifying effect in PD over 1 year. We found pSN free\u2010water increased over 1 year, and baseline free\u2010water relates to clinical motor progression, demonstrating the importance of diffusion imaging parameters for detecting and predicting PD progression. \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28838","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T09:13:23Z","timestamp":1635758003000},"page":"325-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Diffusion Magnetic Resonance Imaging Detects Progression in <scp>Parkinson's<\/scp> Disease: A Placebo\u2010Controlled Trial of Rasagiline"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6442-1205","authenticated-orcid":false,"given":"David J.","family":"Arpin","sequence":"first","affiliation":[{"name":"Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"},{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trina","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"},{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek B.","family":"Archer","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center, Department of Neurology Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Neurology Vanderbilt Genetics Institute, Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana G.","family":"Burciu","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Applied Physiology College of Health Sciences, University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston T.","family":"Chu","sequence":"additional","affiliation":[{"name":"Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"},{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"},{"name":"J. Crayton Pruitt Family Department of Biomedical Engineering University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8708-032X","authenticated-orcid":false,"given":"Thomas","family":"Guttuso","sequence":"additional","affiliation":[{"name":"Movement Disorder Center, Department of Neurology Jacobs School of Medicine &amp; Biomedical Sciences, University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Hess","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology &amp; CTSI Human Imaging Core University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-9223","authenticated-orcid":false,"given":"Irene A.","family":"Malaty","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus R.","family":"McFarland","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Radiology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5994-0644","authenticated-orcid":false,"given":"Catherine C.","family":"Price","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"},{"name":"Departments of Clinical and Health Psychology and Anesthesiology University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna Wagle","family":"Shukla","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Wu","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"},{"name":"Department of Biostatistics University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Okun","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Vaillancourt","sequence":"additional","affiliation":[{"name":"Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"},{"name":"Norman Fixel Institute for Neurological Diseases, Department of Neurology University of Florida  Gainesville Florida USA"},{"name":"J. 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