Motor Dysfunction in REM Sleep Behavior Disorder: A Rehabilitation Framework for Prodromal Synucleinopathy

Abstract

Parkinson disease (PD) and other related diseases with α-synuclein pathology are associated with a long prodromal or preclinical stage of disease. Predictive models based on diagnosis of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) make it possible to identify people in the prodromal stage of synucleinopathy who have a high probability of future disease and provide an opportunity to implement neuroprotective therapies. However, rehabilitation providers may be unaware of iRBD and the motor abnormalities that indicate early motor system dysfunction related to α-synuclein pathology. Furthermore, there is no existing rehabilitation framework to guide early interventions for people with iRBD. The purpose of this work is to (1) review extrapyramidal signs of motor system dysfunction in people with iRBD and (2) propose a framework for early protective or preventive therapies in prodromal synucleinopathy using iRBD as a predictive marker. Longitudinal and cross-sectional studies indicate that the earliest emerging motor deficits in iRBD are bradykinesia, deficits performing activities of daily living, and abnormalities in speech, gait, and posture. These deficits may emerge up to 12 years before a diagnosis of synucleinopathy. The proposed rehabilitation framework for iRBD includes early exercise-based interventions of aerobic exercise, progressive resistance training, and multimodal exercise with rehabilitation consultations to address exercise prescription, progression, and monitoring. This rehabilitation framework may be used to implement neuroprotective, multidisciplinary, and proactive clinical care in people with a high likelihood of conversion to PD, dementia with Lewy bodies, or multiple systems atrophy.

Stemming the Tide: The Proactive Role of Allied Health Therapy in Parkinson’s Disease

“…PT can play an important role in helping PwP optimize guideline-concordant exercise participation through recognition of an individual's unique barriers and facilitators to exercise, tailored exercise prescription, and long-term monitoring [39,44]. The majority of PT and exercise trials include individuals with HY Stage 1-3 [26], but skilled exercise prescription would likely be beneficial in prodromal PD based on epidemiologic research [32]. Exercise prescription is complex, as it involves aerobic, strengthening, balance, and flexibility activities, which can be overwhelming without the guidance of a skilled PT or other experienced exercise professionals [26,52].…”

“…Given the presence of early motor and nonmotor challenges experienced by PwP [5,31], care and outcomes may improve if allied health professionals increase their role in early assessment, education, and intervention compared to current utilization. There may also be a role for allied health therapies to screen for PD-relevant signs or symptoms when prodromal PD is suspected based on the presence of REM sleep behavior disorder (RBD) and/or hyposmia [32].…”

Statistical Considerations in the Design of Clinical Trials Targeting Prodromal Parkinson Disease

“…Options for assessment of motor function include in-clinic tapping and pegboard tasks, remote task-oriented smartphone assessments of tapping and gait (e.g., mPower 11 and the PD Mobile app 12 ), measures of mobility tracked through passive data collection using a wearable device or smartphone, and inclinic or smartphone-based assessments of speech. 13,14 A phase 2a proof-of-concept trial in prodromal PD might be designed for 3-6 months of follow-up of a sample of 36-75 individuals randomized 1:1:1 to placebo and 2 active dosages. Participants should have a high probability of prodromal PD based on the MDS research criteria.…”

“…Options for assessment of motor function include in-clinic tapping and pegboard tasks, remote task-oriented smartphone assessments of tapping and gait (e.g., mPower 11 and the PD Mobile app 12 ), measures of mobility tracked through passive data collection using a wearable device or smartphone, and in-clinic or smartphone-based assessments of speech. 13,14…”

Screening and Targeting Risk Factors for Prodromal Synucleinopathy: Taking Steps toward a Prescriptive Multi-modal Framework

“…The World Health Organization recently identified six challenges to addressing the burden of PD and has placed an urgent call to specifically ‘generate harmonized approaches for PD risk reduction based on existing evidence, with both individual-level and population-level approaches’ [ 10 ]. Heretofore, only one proposal has been offered within the RBD population, based solely on exercise [ 11 ]. Herein, we offer an initial proposal for a ‘prescription’ for a multimodal approach to delaying disease onset at the level of the individual.…”