While animal models have suggested that exercise may be neuroprotective and beneficial for Parkinson's disease (PD),1, 2 exercise-based interventions for humans with PD have been inconclusive.3, 4 For example, exercise approaches such as treadmill walking5, 6 or traditional physical therapy7 have displayed conflicting results. An important consideration is that perhaps, these approaches are not ideal exercise models since they are designed to ameliorate musculoskeletal deficits such as shuffling gait, decreased range of motion, and poor posture while ignoring the potential underlying mechanism of basal ganglia dysfunction. More recently, exercise strategies, such as cueing, have attempted to improve PD-specific symptoms and movement deficits and have shown promising results.
Cueing is the primary symptom specific strategy that has been employed in rehab settings and is based on research displaying that auditory and visual cues can improve the disturbed gait pattern present in PD.8–10 Training using visual and auditory cues in 153 participants resulted in increased velocity, step length, and posture and gait.11 Similar gait improvements have been found following rhythmic auditory stimulation (synchronized beats to music)12 and pacing using a metronome13 during exercise. Two main limitations were present in this research. First, the exercise and outcome measures used were primarily gait focused and it has been suggested that gait-specific impairments such as decreased step length are easily altered, by gait specific training, but may not benefit a patient's day to day activities.4 Additionally, Nieuwboer et al.11 was the only cueing trial that used any clinical measure of PD symptoms and this was only a few specific items within the motor scale ofthe Unified Parkinson's Disease Rating Scale (UPDRS). Thus, it is difficult to ascertain whether the mobility benefits resulting from cueing exercise were in fact disease-specific symptomatic gains or only very specific mobility gains.
Few studies have addressed the previously identified limitations. Researchers have attempted to imply neurological changes using positron emission tomography (PET) suggesting that cueing exercise might lead to cortical reorganization to bypass the defective basal ganglia.14 Unlike other cueing research, Marchese et al. employed a well-designed direct comparison of a cued and noncued group with a specific clinical measure of PD symptoms, the UPDRS. Both groups were found to benefit from the exercise; however, following a 6-week nonexercise period only the cued group retained the benefits of the exercise program.15 Thus, it appears as though the cued exercises were influencing neurophysiology that was more permanent while the noncued exercises likely led to musculoskeletal improvements that were short-lived. Morris et al.16 also performed a well-designed randomized controlled trial to compare movement strategies with traditional-based exercises and found that only the movement strategies intervention, which was designed based on PD neurological deficits, was able to positively improve PD symptoms. These limited results point to potential benefit of sensory cues, however, further study of exercise interventions employing similar well-designed specific comparisons are needed to verify the true benefits of exercise. Furthermore, we need to consider the underlying mechanisms that contribute to PD when designing exercise interventions.
An interesting possibility supported by previous research is that individuals with PD have a deficit in their ability to integrate and utilize sensory, specifically proprioceptive feedback.17, 18 This deficit may stem from the dysfunctional basal ganglia which has been suggested to play an important role in the integration of proprioceptive feedback during movement.17 As such, a novel Sensory Attention Focused Exercise program (PD SAFEx™) was developed which has been shown to improve motor symptoms and functional outcome in PD.19 The PD SAFEx™ program was designed to have participants focus on and utilize proprioceptive feedback while exercising, thus, improving awareness of self motion. The purpose of this study was to compare two exercise programs differing only on the presence (PD SAFEx™) or absence (non-SAFE) of increased attention to sensory feedback to determine whether it would have a specific influence on the symptoms of PD.
This study examined 26 participants with idiopathic PD from the database at the Movement Disorders Research and Rehabilitation Centre (MDRC) who were randomly assigned to receive either the PD SAFEx™ (n = 13; mean age = 66.1, SD = 11.3) or the non-SAFE (n = 13; mean age = 66.8, SD = 9.0) intervention. All participants had a diagnosis of PD with no other major neurological or psychological problems. All medication and supplementary physical activity was unaltered for the duration of the study such that the only addition to a participant's regular schedule was the exercise group assigned for the research. The attendance expectations for participation in these exercise interventions were clearly outlined to participants before enrollment, thus enabling all participants to complete the training. However, three individuals (two in PD SAFEx™, one in non-SAFE) were removed from analysis as their diagnosis was changed to progressive supranuclear palsy by their neurologist after study completion. This research was approved by the research ethics board at Wilfrid Laurier University and all subjects signed informed consent forms before commencement of the study.
There were two groups, PD SAFEx™ and non-SAFE (control group). The non-SAFE program mirrored PD SAFEx™ except that the lights were on, and participant's eyes were open, and the instructions did not focus attention on sensory feedback. PD SAFEx™ was designed to have participants focus on sensory feedback by dimming the lights, having participants close their eyes, and focusing participant's attention on specific portions of each exercise. Thus, consistency was maintained in intervention instruction, length, intensity, and exercise type with the sole difference being whether participants had their eyes open or closed.
Both the PD SAFEx™ and non-SAFE exercise programs were administered simultaneously at the MDRC over a 12-week period followed by a 6-week nonexercise washout period. Both interventions required participants to attend three times per week for ∼1 h. A more complete description of the PD SAFEx™ program has been published previously.19 Briefly, both programs were group settings with ∼15 participants, one instructor and enough student volunteers (senior undergraduate students at Wilfrid Laurier University trained in proper administration of the exercise program) to maintain a 2:1 ratio of participants to volunteers. The volunteers were present to ensure participants' properly completed each exercise and to reinforce the focus onutilizing sensory feedback. The exercise program consisted of ∼30 min of nonaerobic gait exercises followed by 30 min of exercises using office chairs (All Seating Corporation, Model No.3307) with latex Thera-bands® attached to the arm rests for light resistance.
Participants were evaluated at three time periods: (i) before the exercise intervention (pretest); (ii) immediately following the last exercise session (post-test); and (iii) 6 weeks (or within 7 days after the 6 week washout period, to accommodate for scheduling conflicts) following the end of the exercise intervention (washout).
Each participant completed a standardized battery of tests to evaluate symptoms, functional status, and basic movement kinematics. The primary outcome measure was a clinical evaluation of PD symptom severity consisting of the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III).20 The UPDRS was administered at participants' peak anti-parkinsonian medication dosage (same assessment time, ±1 h, at each evaluation) by a trained clinician who was blinded to participants' group assignment. Blinding was achieved by randomly testing participants from both exercise groups on the same day as participants from other research projects. Upper limb motor control was assessed using the Grooved Pegboard (GP) (Lafayette Instruments, Lafayette, IN). Participants completed two trials with each hand following procedures outlined previously.21 Each trial consisted of both a place phase where 25 identical grooved pegs were placed into holes and a remove phase where the pegs were subsequently removed using the same hand. The order of limb testing began randomly and then alternated between limbs until both limbs completed the procedure twice. All participants were self reported right-handed and the place and remove phases of the GP were analyzed based on the most and least affected limb, as identified from side related items measured with the pretest UPDRS. Participants completing the GP in more than 4 min did not complete a second trial and participants unable to complete the GP in 5 min were stopped, a count of pegs completed was taken, and the remove phase was not completed. An average rate of time(s) per peg for the two trials was calculated and used in statistical analysis. Three participants were removed from analysis of the remove phase using the affected limb and one participant was removed from analysis of the remove phase using the nonaffected limb due to failure to complete the task.
Gait was measured in a functional task using two trials of the Timed-Up-and-Go (TUG), which has been shown to be a reliable outcome measure in PD.22 Time to complete the TUG was averaged over two trials. Spatiotemporal aspects of gait (velocity and step length) were measured using five trials of self-paced gait over a 4 m pressure sensitive GAITrite® carpet. Each trial began a minimum of two paces before the carpet and the participant continued walking a minimum of two paces after measurement ceased to ensure acceleration and deceleration were not included in measurement.
Statistical analysis used Statistica® software with an alpha level of 0.05. Each outcome measure was analyzed using group (PD SAFEx™ vs. non-SAFE control) by time (pretest vs. post-test vs. washout) analysis of variance. Significant ANOVA's were followed up using Tukey's HSD post-hoc procedure. The post-hoc comparisons of particular importance were the pretest to post-test and post-test to washout comparisons, to assess the immediate and lasting effects of the exercise programs, respectively.
The two groups were not significantly different in mean age, years since diagnosis or disease severity. Baseline demographics of the two exercise groups are outlined in Table 1. A complete breakdown of all results is provided in Table 2.
Table 1. Mean (±standard deviation) participant demographics for the two groups
Grooved Pegboard affected side remove phase (sec/peg)
Grooved Pegboard nonaffected side remove phase (sec/peg)
Step length (cm)
UPDRS symptom severity score analysis revealed a significant group by time interaction (F(2,48) = 3.62, P < 0.035) (Fig. 1). Post-hoc indicated that only the PD SAFEx™ group had improved UPDRS scores at post-test when compared with pretest (P < 0.035) and the improvements were maintained at washout compared with post-test (P > 0.05). The non-SAFE group did not appreciably alter their UPDRS scores following exercise, however, following the washout period UPDRS scores were significantly higher (i.e., symptoms worsened) when compared with post-test (P < 0.035).
Upper Limb Motor Control
Across both groups, the affected (F(2,42) = 5.62, P < 0.007) and nonaffected (F(2,46) = 13.07, P < 0.001) limbs displayed main effects of time for the remove phase of the GP indicating that post-test was significantly faster than pretest, and the improvement was maintained after the washout period. The place phase of the grooved pegboard did not reveal any significant effects or interactions for either the affected or nonaffected limbs.
Across both groups, a significant main effect of time for the TUG was found (F(2,48) = 4.69, P < 0.014) as the TUG was significantly faster at post-test (compared to pretest) and these improvements were maintained after the washout period.
Step length also revealed a main effect of time (F(2,48) = 3.28, P < 0.046) with a significantly increased step length at post-test compared with both pretest and washout. Velocity approached significance for a main effect of time (F(2,48) = 2.82, P < 0.069) with participants appearing to have increased velocity at post-test compared with pretest.
The aim of this study was to determine the effect of focusing attention to sensory feedback derived from the limbs and body during exercise. Two identical exercise interventions were administered, differing only on whether or not vision was available, and instructions encouraging a focus on using proprioception to guide movement. While both programs demonstrated improved GP remove phase, TUG, and step length measurements, only the PD SAFEx™ program was able to reduce PD symptom severity. Additionally, the symptom improvement identified in the PD SAFEx™ group was maintained after 6 weeks of inactivity. Thus, focusing attention on sensory feedback while exercising appears to have an additive benefit for individuals with PD. These findings are similar to those of Marchese et al. who also did a careful comparison of two very similar exercise programs. The programs differed only in the presence or absence of sensory cues and resulted in improved UPDRS symptom severity scores. Similar to this study, only the sensory cued group maintained the improvements following 6 weeks without exercise.15
Of interest was that post-test revealed identical UPDRS scores of 19.2 for both groups, yet following the 6 week nonexercise period group differences emerged. Specifically, the non-SAFE groups mean UPDRS score had significantly worsened by 5.5 points, whereas the PD SAFEx™ groups UPDRS score showed a nonsignificant change (3.4 points). Further examination of UPDRS scores demonstrates that the PD SAFEx™ group improved by 22%, whereas the non-SAFE group only improved by 5% from pretest to post-test. Additionally, previous research with the PD SAFEx™ program displayed similar results as 18 participants improved their UPDRS scores from 22.5 to 16.9, or 25% following 12 weeks of exercise.19 Thus, although the sample sizes were smaller than ideal, the results of this study were in line with previously reported results.
Between group differences were not identified with the grooved pegboard (GP), since both groups did not improve on the place phase but both groups improved on the remove phase for both affected and nonaffected limbs. The place phase is primarily a visuo-motor task, whereas the remove phase is more a measure of motor speed.21 As the participants in this study were older individuals, perhaps, the place task was too demanding, as six participants (∼25%) required more than 4 min or were unable to complete the task. The remove phase, however, does not require the same accuracy demands and both exercise groups improved their rate on the remove phase indicating improved upper limb motor speed. Specific to PD symptoms the remove phase may be an indicator of one of the cardinal symptoms of PD, bradykinesia (slowness of movement), and the results suggest that both exercise programs improved upper limb bradykinesia.
Functional status was improved in both groups following exercise, supported by the improved time taken to complete the TUG. These results may be relevant to PD symptoms as the TUG specifically evaluates motor impairment issues that are commonly associated with PD such as sit to stand, initiation of gait, and dynamic balance while turning. Of further interest, the benefits were maintained in both groups following the 6-week nonexercise period.
The improvements in spatiotemporal aspects of gait following exercise were minor, as the significant main effect of step length at post-test was the result of a mean 2 cm increase. As previously mentioned, minimal improvements were not surprising as neither exercise program had a specific focus on gait. However, the combined increases in velocity and step length were suggestive of a more normalized gait pattern. Specific impairments such as spatiotemporal aspects of gait have been shown to be easily influenced but are suggested to be inconsequential to a patients day to day life.4 Thus, the minor gait improvements identified in this study are secondary as the focus was on global improvement of PD symptoms.
There is growing evidence that sensory attention focused exercise programs have a positive influence on the specific motor symptoms of PD.19 Perhaps more importantly, only the PD SAFEx™ group maintained symptom improvements following the washout period, whereas the non-SAFE program resulted in a dramatic decline after washout. Thus, benefits associated with PD SAFEx™ may be the result of an alternate cortical organization that bypasses a faulty basal ganglia, or a greater attempt to consciously process sensory feedback (when eyes are closed) to overcome a dependency on vision in PD during online control of movement.
Future research into the neurophysiological changes and underlying mechanism responsible for the symptomatic benefit of this specific exercise manipulation is warranted. One interesting direction is to assess symptom changes on the most and least affected body side. This would provide important information about neural changes and the functioning level of the contralateral basal ganglia as it has been suggested that more severe PD does not respond well neurophysiologically to exercise.23, 24 Interestingly, in this study, the PD SAFEx™ group had improvements of 27.4% and 15.0% compared with 4.26% and 4.54% for the non-SAFE group on the most and least affected sides of the body, respectively.
Overall, the lasting symptomatic improvements witnessed in the PD SAFEx™ group suggest that the benefit is not simply musculoskeletal but the result of improved neurological function. While the group sizes were relatively small, this is a significant finding since improving neurological symptoms may be more difficult than improving musculoskeletal (i.e., mobility) impairments.3 Thus, the increased focus on sensory feedback in the PD SAFEx™ appears to provide an additive symptomatic benefit for individuals with PD.
This research was generously supported by the Parkinson's Society Canada.
Financial Disclosures: Nothing to report.
Michael Sage—organization and execution of research project, statistical analysis design and execution, writing of first draft, review of manuscript. Dr. Quincy Almeida—conception, organization, and execution of research project, statistical analysis review and critique, review and critique of manuscript.