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

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

An Artificial Intelligence Video-Based Assessment of Upper-limb Bradykinesia in Parkinson’s Disease

“…The substantia nigra has a critical role in modulating motor movement and reward functions as part of the basal ganglia circuitry, and substantia nigra degeneration is the involved in the motor deficits observed in PD (Hodge & Butcher, 1980;Purves et al, 2001). Measurements of free water in the pSN have emerge as a reliable objective marker of disease progression in PD (Arpin et al, 2022). Our finding provides initial evidence that low-cost, video-based movement measures are linearly related to well-establish objective markers of disease progression in PD.…”

“…This study employed clinical, imaging, and video data collected as a part of a previously completed clinical trial (Arpin et al, 2022). Table 1 summarizes the demographic information for the individuals selected for this study.…”

“…Major international initiatives such as the Parkinson's Disease Biomarkers Program and Parkinson's Progression Markers Initiative demonstrate a growing interest in developing objective markers that support diagnosis and monitoring of disease progression (Marek et al, 2011;Rosenthal et al, 2016). One such marker, known as Free Water in the Substantia Nigra (pSN) has emerged as a reliable imaging biomarker for detecting Parkinsonism in early stages of the disease (Arpin et al, 2022;Zhou et al, 2021), and tracking disease progression (Guttuso et al, 2018;Ofori et al, 2015). Free water in the pSN is a valid imaging marker of neurodegeneration in idiopathic REM sleep behavior disorder, a preclinical model of parkinsonism (Fulda, 2011;Zhou et al, 2021), and can help to differentiate PD from people suffering from other synucleinopathies (Mitchell et al, 2022).…”

Monitoring Substantia Nigra Degeneration Using Free Water Imaging across Prodromal and Clinical Parkinson's Disease

“…In addition, rasagiline has been widely recognized for its neuroprotective effects 49 ; a previous retrospective study showed that PD patients with a history of rasagiline use had lower free water values in the PSN than those who had not chronically taken this medication 24 . Another randomized controlled study 25 found a four times greater increase in pSN free water in PD randomized to placebo compared to PD randomized to rasagiline. However, we did not find any differences between patients treated with and without MAO‐B inhibitors.…”

“…Free water values in the ASN and PSN were compared across the four groups using analysis of covariance, adjusting for age, sex, and education. To understand whether MAO‐B (monoamine oxidase inhibitor‐B) treatment affects SN free water, 25 we divided the mPD group based on whether they had chronically used MAO‐B and compared the two groups. The relationship between clinical outcomes and PSN free water values in the pPD, dnPD, and mPD groups was investigated using multivariable linear regression analysis, controlling for age, sex, and education in pPD patients and these three variables in addition to disease duration in dnPD and mPD patients.…”