David J Arpin1,2, Trina Mitchell1,2, Derek B Archer3,4, Roxana G Burciu5, Winston T Chu1,2,6, Hanzhi Gao7, Thomas Guttuso8, Christopher W Hess2, Song Lai9, Irene A Malaty2, Nikolaus R McFarland2, Ofer Pasternak10, Catherine C Price2,11, Aparna Wagle Shukla2, Samuel S Wu2,7, Michael S Okun2, David E Vaillancourt1,2,6. 1. Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA. 2. Norman Fixel Institute for Neurological Diseases, Department of Neurology, University of Florida, Gainesville, Florida, USA. 3. Vanderbilt Memory and Alzheimer's Center, Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 4. Department of Neurology, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 5. Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, Delaware, USA. 6. J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA. 7. Department of Biostatistics, University of Florida, Gainesville, Florida, USA. 8. Movement Disorder Center, Department of Neurology, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo, Buffalo, New York, USA. 9. Department of Radiation Oncology & CTSI Human Imaging Core, University of Florida, Gainesville, Florida, USA. 10. Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 11. Departments of Clinical and Health Psychology and Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA.
Abstract
BACKGROUND: Rasagiline has received attention as a potential disease-modifying therapy for Parkinson's disease (PD). Whether rasagiline is disease modifying remains in question. OBJECTIVE: The main objective of this study was to determine whether rasagiline has disease-modifying 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. METHODS: This prospective, randomized, double-blind, placebo-controlled trial assessed the effects of rasagiline administered at 1 mg/day over 12 months in early-stage PD. The primary outcome was 1-year change in free-water accumulation in posterior substantia nigra (pSN) measured using two diffusion magnetic resonance imaging pulse sequences, one with a repetition time (TR) of 2500 ms (short TR; n = 90) and one with a TR of 6400 ms (long TR; n = 75). Secondary clinical outcomes also were assessed. RESULTS: Absolute change in pSN free-water accumulation was not significantly different between groups (short TR: P = 0.346; long TR: P = 0.228). No significant differences were found in any secondary clinical outcomes between groups. Long TR, but not short TR, data show pSN free-water increased significantly over 1 year (P = 0.025). Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III increased significantly over 1 year (P = 0.009), and baseline free-water in the pSN correlated with the 1-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III (P = 0.004) and 1-year change in bradykinesia score (P = 0.044). CONCLUSIONS: We found no evidence that 1 mg/day rasagiline has a disease-modifying effect in PD over 1 year. We found pSN free-water increased over 1 year, and baseline free-water relates to clinical motor progression, demonstrating the importance of diffusion imaging parameters for detecting and predicting PD progression.
BACKGROUND: Rasagiline has received attention as a potential disease-modifying therapy for Parkinson's disease (PD). Whether rasagiline is disease modifying remains in question. OBJECTIVE: The main objective of this study was to determine whether rasagiline has disease-modifying 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. METHODS: This prospective, randomized, double-blind, placebo-controlled trial assessed the effects of rasagiline administered at 1 mg/day over 12 months in early-stage PD. The primary outcome was 1-year change in free-water accumulation in posterior substantia nigra (pSN) measured using two diffusion magnetic resonance imaging pulse sequences, one with a repetition time (TR) of 2500 ms (short TR; n = 90) and one with a TR of 6400 ms (long TR; n = 75). Secondary clinical outcomes also were assessed. RESULTS: Absolute change in pSN free-water accumulation was not significantly different between groups (short TR: P = 0.346; long TR: P = 0.228). No significant differences were found in any secondary clinical outcomes between groups. Long TR, but not short TR, data show pSN free-water increased significantly over 1 year (P = 0.025). Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III increased significantly over 1 year (P = 0.009), and baseline free-water in the pSN correlated with the 1-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III (P = 0.004) and 1-year change in bradykinesia score (P = 0.044). CONCLUSIONS: We found no evidence that 1 mg/day rasagiline has a disease-modifying effect in PD over 1 year. We found pSN free-water increased over 1 year, and baseline free-water relates to clinical motor progression, demonstrating the importance of diffusion imaging parameters for detecting and predicting PD progression.
Authors: Karl Kieburtz; Barbara C Tilley; Jordan J Elm; Debra Babcock; Robert Hauser; G Webster Ross; Alicia H Augustine; Erika U Augustine; Michael J Aminoff; Ivan G Bodis-Wollner; James Boyd; Franca Cambi; Kelvin Chou; Chadwick W Christine; Michelle Cines; Nabila Dahodwala; Lorelei Derwent; Richard B Dewey; Katherine Hawthorne; David J Houghton; Cornelia Kamp; Maureen Leehey; Mark F Lew; Grace S Lin Liang; Sheng T Luo; Zoltan Mari; John C Morgan; Sotirios Parashos; Adriana Pérez; Helen Petrovitch; Suja Rajan; Sue Reichwein; Jessie Tatsuno Roth; Jay S Schneider; Kathleen M Shannon; David K Simon; Tanya Simuni; Carlos Singer; Lewis Sudarsky; Caroline M Tanner; Chizoba C Umeh; Karen Williams; Anne-Marie Wills Journal: JAMA Date: 2015-02-10 Impact factor: 56.272
Authors: Edward Ofori; Ofer Pasternak; Peggy J Planetta; Hong Li; Roxana G Burciu; Amy F Snyder; Song Lai; Michael S Okun; David E Vaillancourt Journal: Brain Date: 2015-05-16 Impact factor: 13.501
Authors: A Kupsch; J Sautter; M E Götz; W Breithaupt; J Schwarz; M B Youdim; P Riederer; M Gerlach; W H Oertel Journal: J Neural Transm (Vienna) Date: 2001 Impact factor: 3.575
Authors: Derek B Archer; Justin T Bricker; Winston T Chu; Roxana G Burciu; Johanna L Mccracken; Song Lai; Stephen A Coombes; Ruogu Fang; Angelos Barmpoutis; Daniel M Corcos; Ajay S Kurani; Trina Mitchell; Mieniecia L Black; Ellen Herschel; Tanya Simuni; Todd B Parrish; Cynthia Comella; Tao Xie; Klaus Seppi; Nicolaas I Bohnen; Martijn L T M Müller; Roger L Albin; Florian Krismer; Guangwei Du; Mechelle M Lewis; Xuemei Huang; Hong Li; Ofer Pasternak; Nikolaus R McFarland; Michael S Okun; David E Vaillancourt Journal: Lancet Digit Health Date: 2019-08-27
Authors: Trina Mitchell; Stéphane Lehéricy; Shannon Y Chiu; Antonio P Strafella; A Jon Stoessl; David E Vaillancourt Journal: JAMA Neurol Date: 2021-10-01 Impact factor: 29.907
Authors: Jesper L R Andersson; Mark S Graham; Ivana Drobnjak; Hui Zhang; Nicola Filippini; Matteo Bastiani Journal: Neuroimage Date: 2017-03-08 Impact factor: 6.556
Authors: Trina Mitchell; Bradley J Wilkes; Derek B Archer; Winston T Chu; Stephen A Coombes; Song Lai; Nikolaus R McFarland; Michael S Okun; Mieniecia L Black; Ellen Herschel; Tanya Simuni; Cynthia Comella; Mitra Afshari; Tao Xie; Hong Li; Todd B Parrish; Ajay S Kurani; Daniel M Corcos; David E Vaillancourt Journal: Neuroimage Clin Date: 2022-04-26 Impact factor: 4.891