Diffusion Magnetic Resonance Imaging Detects Progression in Parkinson's Disease: A Placebo-Controlled Trial of Rasagiline

David J Arpin^{1

2}, Trina Mitchell^{1

2}, Derek B Archer^{3

4}, Roxana G Burciu⁵, Winston T Chu^{1

2

6}, Hanzhi Gao⁷, Thomas Guttuso⁸, Christopher W Hess², Song Lai⁹, Irene A Malaty², Nikolaus R McFarland², Ofer Pasternak¹⁰, Catherine C Price^{2

11}, Aparna Wagle Shukla², Samuel S Wu^{2

7}, Michael S Okun², David E Vaillancourt^{1

2

6}

Affiliations

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.

PMID: 34724257
PMCID: PMC9019575
DOI: 10.1002/mds.28838

Randomized Controlled Trial

Diffusion Magnetic Resonance Imaging Detects Progression in Parkinson's Disease: A Placebo-Controlled Trial of Rasagiline

David J Arpin et al. Mov Disord. 2022 Feb.

. 2022 Feb;37(2):325-333.

doi: 10.1002/mds.28838. Epub 2021 Nov 1.

Authors

Affiliations

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.

PMID: 34724257
PMCID: PMC9019575
DOI: 10.1002/mds.28838

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. © 2021 International Parkinson and Movement Disorder Society.

Keywords: MAO-B; Parkinson's; diffusion imaging; progression; rasagiline.

PubMed Disclaimer

Conflict of interest statement

Relevant conflicts of interest/financial disclosures: The authors report no conflicts of interest relevant to this research.

Full financial disclosures and author roles may be found in the online version of this article.

Figures

**FIG. 1.**
Participant enrollment and randomization. Of the 90 participants randomized, 11 did not return for follow-up visit.

See this image and copyright information in PMC

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Diffusion Magnetic Resonance Imaging Detects Progression in Parkinson's Disease: A Placebo-Controlled Trial of Rasagiline

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Diffusion Magnetic Resonance Imaging Detects Progression in Parkinson's Disease: A Placebo-Controlled Trial of Rasagiline

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