Background-Dopamine replacement medication has positive effects on existing motor skills for people with Parkinson disease (PD), but may have detrimental effects on the learning of motor skills necessary for effective rehabilitation according to the dopamine overdose hypothesis.Objectives-This study aimed to determine whether dopamine replacement medication (i.e. levodopa) affects: learning of a novel upper extremity task, decrements in skill following withdrawal of practice, the rate of learning, and the transfer of movement skill to untrained upper extremity tasks compared to training "off" medication, in people with PD.Methods-Participants with mild-moderate PD (Hoehn and Yahr stage 2) were randomized to train "on" (n=12) or "off" (n=11) levodopa medication. Participants practiced 10 blocks of five trials of a functional motor task with their non-dominant upper extremity over three consecutive days (acquisition period), followed by a single block of five trials two and nine days later.

Background and Purpose: Skill acquisition (ie, performance changes during practice) occurs in a nonlinear fashion. Despite this, motor learning is typically measured by comparing discrete timepoints. Thus, typical measures of motor learning do not detect skill acquisition characteristics that may be clinically meaningful. Reliable prediction of motor skill learning in people with Parkinson disease (PD) would allow therapists to more effectively individualize practice doses to fit specific patients' needs. The purposes of this study were to (a) characterize postural skill acquisition in people with PD, and identify factors (such as acquisition rate and practice dose to plateau) that predict learning, and (b) investigate whether levodopa medication (l-dopa) status during practice impacted learning. Methods: Twenty-seven adults with PD practiced a postural motor task over 3 days, followed by 2 retention tests. Participants were randomized to practice either ON or OFF l-dopa. Data for repeating and random sequences were each analyzed using nonlinear curve-fitting and mixed-effects regressions. Learning was defined as pretest minus retention test performance. Results: Participants with less physical impairment demonstrated less learning on the repeating and random sequence tasks compared with participants with more impairment. Participants who improved faster during practice demonstrated less learning on the repeating sequence task compared with participants who improved more slowly. Reaching plateau during practice was not related to learning. l-dopa did not impair learning. Discussion and Conclusions: Participants' skill acquisition characteristics were related to learning a postural motor task. Patient-specific factors, such as the rate of skill acquisition, level of physical function, and medication status, may influence how postural motor practice is delivered during balance rehabilitation. Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A250).

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Introduction. Treatment of Parkinson's disease (PD) with exogenous dopamine (ie, levodopa) may positively affect motor symptoms, but may negatively affect other functions such as the learning of motor skills necessary for rehabilitation. This study aimed to determine whether levodopa medication affects general and sequence-specific learning of a stepping task and the transfer of movement skill to untrained balance tasks in people with PD. Methods. Participants with PD were randomized to practice "on" (n = 14) or "off" (n = 13) levodopa medication. Participants practiced 6 blocks of 6 trials of 24 steps of a stepping task over an acquisition period of 3 consecutive days, followed by single retention blocks of 6 trials 2 and 9 days later. Participants were also assessed on untrained balance (ie, transfer) tasks "on" levodopa before practice and following late retention. Results. There were no between-group differences in general learning, sequence-specific learning, or transfer of skill to untrained balance tasks (P > .05). Both groups demonstrated general and sequence-specific learning (P < .001) and trends for improvement in untrained tasks (P < .001 to P = .26) following practice. Detailed analysis of early acquisition revealed no difference between medication groups. Conclusion. People with PD improved performance on the stepping task with practice. The between-group effect sizes were small, suggesting that levodopa medication status ("on" versus "off") during practice did not significantly affect general or sequence-specific learning of the task or components of early acquisition. The practice dose required to optimally result in functional improvements in untrained balance tasks, including reductions in falls, remains to be determined.

Background To date, no medication has slowed the progression of Parkinson’s disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. Methods This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60–65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80–85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. Discussion SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health. Trial registration ClinicalTrials.govNCT04284436. Registered on February 25, 2020.