Cynthia Poon

A two-year randomized controlled trial of progressive resistance exercise for Parkinson's disease

The effects of progressive resistance exercise (PRE) on the motor signs of Parkinsons disease have not been studied in controlled trials. The objective of the current trial was to compare 6‐, 12‐, 18‐, and 24‐month outcomes of patients with Parkinsons disease who received PRE with a stretching, balance, and strengthening exercise program. The authors conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients matched by sex and off‐medication scores on the Unified Parkinsons Disease Rating Scale, motor subscale (UPDRS‐III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight‐lifting program. The modified fitness counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised 2 days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first 6 months and 1 weekly session after 6 months. The primary outcome was the off‐medication UPDRS‐III score. Patients were followed for 24 months at 6‐month intervals. Of 51 patients, 20 in the PRE group and 18 in the mFC group completed the trial. At 24 months, the mean off‐medication UPDRS‐III score decreased more with PRE than with mFC (mean difference, −7.3 points; 95% confidence interval, −11.3 to −3.6; P<0.001). The PRE group had 10 adverse events, and the mFC group had 7 adverse events. PRE demonstrated a statistically and clinically significant reduction in UPDRS‐III scores compared with mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs.

Exercise improves cognition in Parkinson's disease: The PRET-PD randomized, clinical trial.

This article reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes that were gathered as part of the Progressive Resistance Exercise Training in Parkinsons disease (PD) randomized, controlled trial.

Two-year exercise program improves physical function in Parkinson's disease: the PRET-PD randomized clinical trial.

Background. The progressive resistance exercise (PRE) in Parkinson’s disease trial (PRET-PD) showed that PRE improved the motor signs of PD compared to a modified Fitness Counts (mFC) program. It is unclear how long-term exercise affects physical function in these individuals. Objective. To examine the effects of long-term PRE and mFC on physical function outcome measures in individuals with PD. Methods. A preplanned secondary analysis was conducted using data from the 38 patients with idiopathic PD who completed the PRET-PD trial. Participants were randomized into PRE or mFC groups and exercised 2 days/week up to 24 months. Blinded assessors obtained functional outcomes on and off medication at baseline, 6 and 24 months with the Modified Physical Performance Test, 5 times sit to stand test, Functional Reach Test, Timed Up and Go, Berg Balance Scale, 6 minute walk test (6MWT), and 50-ft walking speed (walk speed). Results. The groups did not differ on any physical function measure at 6 or 24 months (Ps > .1). Across time, all physical function measures improved from baseline to 24 months when tested on medication (Ps < .0001), except for 6MWT (P = .068). Off medication results were similar except that the 6MWT was now significant. Conclusions. Twenty-four months of supervised and structured exercise (either PRE or mFC) is effective at improving functional performance outcomes in individuals with moderate PD. Clinicians should strive to include structured and supervised exercise in the long-term plan of care for individuals with PD.

Two-Year Exercise Program Improves Physical Function in Parkinson’s Disease

Background. The progressive resistance exercise (PRE) in Parkinson’s disease trial (PRET-PD) showed that PRE improved the motor signs of PD compared to a modified Fitness Counts (mFC) program. It is unclear how long-term exercise affects physical function in these individuals. Objective. To examine the effects of long-term PRE and mFC on physical function outcome measures in individuals with PD. Methods. A preplanned secondary analysis was conducted using data from the 38 patients with idiopathic PD who completed the PRET-PD trial. Participants were randomized into PRE or mFC groups and exercised 2 days/week up to 24 months. Blinded assessors obtained functional outcomes on and off medication at baseline, 6 and 24 months with the Modified Physical Performance Test, 5 times sit to stand test, Functional Reach Test, Timed Up and Go, Berg Balance Scale, 6 minute walk test (6MWT), and 50-ft walking speed (walk speed). Results. The groups did not differ on any physical function measure at 6 or 24 months (Ps > .1). Across time, all physical function measures improved from baseline to 24 months when tested on medication (Ps < .0001), except for 6MWT (P = .068). Off medication results were similar except that the 6MWT was now significant. Conclusions. Twenty-four months of supervised and structured exercise (either PRE or mFC) is effective at improving functional performance outcomes in individuals with moderate PD. Clinicians should strive to include structured and supervised exercise in the long-term plan of care for individuals with PD.

Spatiotemporal dynamics of brain activity during the transition from visually guided to memory-guided force control

It is well established that the prefrontal cortex is involved during memory-guided tasks whereas visually guided tasks are controlled in part by a frontal-parietal network. However, the nature of the transition from visually guided to memory-guided force control is not as well established. As such, this study examines the spatiotemporal pattern of brain activity that occurs during the transition from visually guided to memory-guided force control. We measured 128-channel scalp electroencephalography (EEG) in healthy individuals while they performed a grip force task. After visual feedback was removed, the first significant change in event-related activity occurred in the left central region by 300 ms, followed by changes in prefrontal cortex by 400 ms. Low-resolution electromagnetic tomography (LORETA) was used to localize the strongest activity to the left ventral premotor cortex and ventral prefrontal cortex. A second experiment altered visual feedback gain but did not require memory. In contrast to memory-guided force control, altering visual feedback gain did not lead to early changes in the left central and midline prefrontal regions. Decreasing the spatial amplitude of visual feedback did lead to changes in the midline central region by 300 ms, followed by changes in occipital activity by 400 ms. The findings show that subjects rely on sensorimotor memory processes involving left ventral premotor cortex and ventral prefrontal cortex after the immediate transition from visually guided to memory-guided force control.

Combined measures of movement and force variability distinguish Parkinson’s disease from essential tremor

OBJECTIVE To examine whether behavioral and electrophysiological measures of motor performance accurately differentiate Parkinsons disease (PD) and essential tremor (ET). METHODS Twenty-four patients (12 PD; 12 ET) performed isometric force, ballistic movements, and tremor tasks. Receiver operating characteristic (ROC) analyses were conducted on all dependent measures that were significantly different between the two patient groups. RESULTS Patients with PD were more impaired on measures of movement deceleration than ET. Patients with ET were more impaired on measures of force variability than PD. ROC analyses revealed that sensitivity and specificity were excellent when combining measures during the isometric force task (torque rise time and force variability; 92% sensitivity and 92% specificity; AUC = 0.97). When combining measures across the force and movement tasks, the ROC analysis revealed improved sensitivity and specificity (force variability and peak deceleration; 92% sensitivity and 100% specificity; AUC = 0.99). CONCLUSIONS Combining measures of force variability and movement deceleration accurately differentiate patients with PD from those with ET with high sensitivity and specificity. SIGNIFICANCE If validated in a larger sample, these measures can serve as markers to confirm the diagnosis of PD or ET and thus, enhance decision making for appropriate treatments for patients with these respective diseases.

Proprioceptive feedback during point-to-point arm movements is tuned to the expected dynamics of the task

It has previously been found that in point-to-point movements against inertial loads, proprioceptive feedback is centrally suppressed in the beginning of movement and is facilitated at a time that is correlated with the expected time of peak velocity. This suggests that the modulation of proprioceptive feedback is governed by the desired movement kinematics. Here we show that in movements against inertial and viscous loads, the correlation of the time when the feedback is facilitated is strongest with the time when the joint torque is expected to be maximal. This suggests that the modulation of proprioceptive feedback is governed by the desired movement dynamics. We applied unexpected perturbations in point-to-point elbow flexion movements against known light and heavy inertial and viscous loads and determined the time and magnitude of responses in the electromyogram (EMG) of the biceps and triceps muscles. In movements against the inertial and viscous loads, the time of the EMG responses was better predicted by the time of the peak joint torque in the unperturbed movement than by the time of peak velocity or the time of peak acceleration or by measures related to the agonist EMG. Moreover, the EMG response changed from a reciprocal pattern in the inertial load conditions to a co-contraction pattern in the viscous load conditions. Our results suggest that during movements against known stable dynamic loads, proprioceptive feedback is tuned to the expected task dynamics and is facilitated so as to maintain muscle stiffness at a time when the muscles are expected to generate maximal force.

Progressive resistance exercise restores some properties of the triphasic EMG pattern and improves bradykinesia: the PRET-PD randomized clinical trial

In Parkinsons disease (PD), the characteristic triphasic agonist and antagonist muscle activation pattern during ballistic movement is impaired: the number of agonist muscle bursts is increased, and the amplitudes of the agonist and antagonist bursts are reduced. The breakdown of the triphasic electromyographic (EMG) pattern has been hypothesized to underlie bradykinesia in PD. Progressive resistance exercise has been shown to improve clinical measures of bradykinesia, but it is not clear whether the benefits for bradykinesia are accompanied by changes in agonist and antagonist muscle activity. This study examined the spatiotemporal changes in agonist and antagonist muscle activity following 24 mo of progressive resistance exercise and the combined relationship between spatiotemporal muscle activity and strength measures and upper limb bradykinesia. We compared the effects of progressive resistance exercise training (PRET) with a nonprogressive exercise intervention, modified Fitness Counts (mFC), in patients with PD. We randomized 48 participants with mild-to-moderate PD to mFC or PRET. At the study endpoint of 24 mo, participants randomized to PRET compared with mFC had significantly faster movement velocity, accompanied by significant increases in the duration, magnitude, and magnitude normalized to duration of the 1st agonist burst and fewer number of agonist bursts before peak velocity. The antagonist muscle activity was increased relative to baseline but did not differ between groups. Spatiotemporal EMG muscle activity and muscle strength were significantly associated with upper limb bradykinesia. These findings demonstrate that progressive resistance exercise improves upper limb movement velocity and restores some aspects of the triphasic EMG pattern.

Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial

Importance Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. Objectives To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. Design, Setting, and Participants The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). Interventions High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. Main Outcomes and Measures Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson’s Disease Rating Scale motor score. Results A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson’s Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, −1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe. Conclusions and Relevance High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease. Trial Registration clinicaltrials.gov Identifier: NCT01506479

Transient shifts in frontal and parietal circuits scale with enhanced visual feedback and changes in force variability and error

When subjects perform a learned motor task with increased visual gain, error and variability are reduced. Neuroimaging studies have identified a corresponding increase in activity in parietal cortex, premotor cortex, primary motor cortex, and extrastriate visual cortex. Much less is understood about the neural processes that underlie the immediate transition from low to high visual gain within a trial. This study used 128-channel electroencephalography to measure cortical activity during a visually guided precision grip task, in which the gain of the visual display was changed during the task. Force variability during the transition from low to high visual gain was characterized by an inverted U-shape, whereas force error decreased from low to high gain. Source analysis identified cortical activity in the same structures previously identified using functional magnetic resonance imaging. Source analysis also identified a time-varying shift in the strongest source activity. Superior regions of the motor and parietal cortex had stronger source activity from 300 to 600 ms after the transition, whereas inferior regions of the extrastriate visual cortex had stronger source activity from 500 to 700 ms after the transition. Force variability and electrical activity were linearly related, with a positive relation in the parietal cortex and a negative relation in the frontal cortex. Force error was nonlinearly related to electrical activity in the parietal cortex and frontal cortex by a quadratic function. This is the first evidence that force variability and force error are systematically related to a time-varying shift in cortical activity in frontal and parietal cortex in response to enhanced visual gain.