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- PATIENTS AND METHODS
Parkinson's disease (PD) is a neurodegenerative disorder affecting the physical, psychological, social, and functional status of individuals. Exercise programs may be an effective strategy to delay or reverse functional decline for people with PD and a large body of empirical evidence has emerged in recent years. The objective is to systematically review randomized controlled trials (RCTs) reporting on the effectiveness of exercise interventions on outcomes (physical, psychological or social functioning, or quality of life) for people with PD. RCTs meeting the inclusion criteria were identified by systematic searching of electronic databases. Key data were extracted by two independent researchers. A mixed methods approach was undertaken using narrative, vote counting, and random effects meta-analysis methods. Fourteen RCTs were included and the methodological quality of most studies was moderate. Evidence supported exercise as being beneficial with regards to physical functioning, health-related quality of life, strength, balance and gait speed for people with PD. There was insufficient evidence support or refute the value of exercise in reducing falls or depression. This review found evidence of the potential benefits of exercise for people with PD, although further good quality research is needed. Questions remain around the optimal content of exercise interventions (dosing, component exercises) at different stages of the disease. © 2008 Movement Disorder Society
Exercise is a planned, structured physical activity which aims to improve one or more aspects of physical fitness.1 Current models of rehabilitation often use compensatory strategies as the basis of therapeutic management. However, there is a growing body of evidence regarding the benefits of exercise in terms of neuroplasticity and the ability of the brain to self repair.2 Animal models have found that exercise has protective benefits against the onset of symptoms in Parkinson's disease (PD).3 This appears to be due to the release of neurotrophic factors, and greater cerebral oxygenation, which together promote new cell growth and cell survival.4, 5 In PD, it has been found that exercise stimulates dopamine synthesis in remaining dopaminergic cells and thus reducing symptoms.6 Fox et al.5 suggest there are five key principles of exercise that enhance neuroplasticity in relation to PD, these being: (a) intensive activity maximizes synaptic plasticity; (b) complex activities promote greater structural adaptation; (c) activities that are rewarding increase dopamine levels and therefore promote learning/relearning; (d) dopaminergic neurones are highly responsive to exercise and inactivity (“use it or lose it”); (e) where exercise is introduced at an early stage of the disease, progression can be slowed.
It has been well documented that physical activity levels decline with advancing age and these reductions contribute to functional decline.7 People with PD have been shown to reduce levels of physical activity more quickly than their healthy peers8 and have lower levels of strength and functional ability.9, 10 However, the observation of muscle weakness is not simply a secondary consequence of ageing and inactivity, but also a primary symptom of PD.11 This is due to impaired basal ganglia having an inadequate effect on the cortical motor centers which in turn lead to less activation of motor neurones and therefore muscle weakness.10, 12 This mechanism also contributes to impaired balance, falls, and disability.13 People with PD are three times more likely to sustain a hip fracture as a result of a fall when compared to those without the condition.14, 15
A number of systematic reviews16–18 and a meta-analysis19 have been undertaken to investigate the efficacy of physiotherapy among people with PD. The earlier reviews, with literature searches up until 199919 and 2000,16, 17 evaluated a range of physiotherapeutic techniques including nonexercise interventions, such as sensory cueing and behavioral therapy, in addition to exercise strategies. The Cochrane reviews16, 17 were limited to randomized controlled trials and reported that they were unable to combine the studies for meta-analysis given the clinical and methodological heterogeneity. The studies were not conclusive in respect to the physiotherapy management of people with PD. De Goede at al19 included studies that adopted a quasi-experimental design. They reported significant benefits in respect of activities of daily living, walking speed, and stride length. However, only one study in each of these domains was a randomized controlled trial evaluating an exercise intervention, with the others using less rigorous study designs or other physiotherapy techniques.
A recent review of physiotherapy for people with PD (literature searches to June 2006) concluded that there were positive benefits associated with gait, transfers, balance and functional ability.18 However, by including a range of management strategies, such as exercise and cueing, under the umbrella of “physiotherapy ” it is difficult to extract information regarding the contribution of individual therapeutic components. Lim et al.,20 for example, reviewed the literature on the effects of cueing on gait in people with PD and reported that while auditory cueing may be beneficial to gait speed, no conclusions could be made as to the effects of visual cueing due to a lack of evidence. Nieuwboer et al.21 recently reported significant improvements is gait and balance using external cueing devices and recommended cueing training as an adjunct to gait management.
This systematic review examines the potential benefit of exercise interventions for people with PD, focusing specifically on evaluations adopting experimental, randomized designs. We did not include studies explicitly evaluating cueing strategies as cueing itself is not an exercise but an external temporal or spatial stimulation to facilitate gait.21
- Top of page
- PATIENTS AND METHODS
The aim of this systematic review was to evaluate the effectiveness of exercise interventions in randomized controlled trials undertaken with people with PD. Our study supports and updates the findings of previous reviews,16–19 and, through refining our scope to one aspect of physiotherapy (i.e., exercise-based interventions) we have identified that exercise is of benefit to people with PD in respect of physical functioning, HRQOL, strength, balance and gait speed. Our findings add to the growing body of evidence regarding the effectiveness of physiotherapy for people with PD.18 There is currently insufficient evidence to support or refute the value of exercise in reducing falls or depression, or its safety with people with PD. We however acknowledge that there is some potential for publication bias as we limited our selection criteria to those studies available in English. We also recognize that there may be confounding from other physiotherapy techniques, such as cueing, as it is difficult to control for this when delivering complex, multi-faceted interventions.
Most studies provided an inadequate description of their methods to allow a full assessment of their methodological quality. Where details reported were available, most studies were found to be of moderate quality using the modified Jadad score. Deane et al.16, 17 had reported that many studies were of poor methodological quality and had small participant numbers when reviewing the effectiveness of physiotherapy techniques (which may include exercise) in people with PD, suggesting that methodological quality can be an issue in studies of this type. Given the generally relatively small sample size of most trials, a lack of statistically significant difference between groups may simply reflect a lack of statistical power rather than the absence of a real lack of difference. However, our pooling of the results for some outcomes across studies allowed us to at least partly overcome the criticism of inadequate power.
The participants were mainly men although the prevalence of PD is said to be similar for men and women43 suggesting that males are somewhat over-represented in these studies. Similarly no studies reported the ethnicity of participants. These raise the questions as to whether these interventions are acceptable to women with PD and the generalizability of the results.
The failure to report a clear rationale behind the development of the intervention may contribute to some of the equivocal findings. It is essential that a “complex intervention ” such as exercise training have a theoretical basis44 in order to inform the design of a study. The interventions described in this review were often short in duration with six studies providing an intervention of 8 weeks or less in duration. This dose of exercise may be insufficient to significantly affect the outcomes.45 Some studies described their intervention as “physiotherapy” which may be considered by some to not be a form of exercise. However in these studies the authors describe in more detail the content of the interventions which utilize exercise as the main component supporting their inclusion in the review.
The studies reviewed in this paper were comparable, in that they targeted the same population (people with PD) using exercise as an intervention and reported outcomes that displayed some similarities, although the length of follow-up varied widely. Most of the studies assessed outcomes at three time points in order to establish any detraining effects after the intervention period had ceased. This is an important factor in clinical practice. Even though we attempted to tighten the focus of this review, the degree to which the studies are clinically and methodologically homogeneous remains debatable. Although the test for statistical heterogeneity was not significant for the papers reporting HRQOL it cannot be assumed that they are homogenous.46 Vote counting was used to supplement the narrative and meta-analyses and to synthesize the results of the included studies given their substantial heterogeneity in outcome reporting. The method provides an overall summary of direction of effect although it does not consider the magnitude of the effect size and the precision of the estimated effects. However, in this review it did provide an approach for summarizing the effect of exercise reported across all studies whereas meta-analysis (which formally takes into account both directionality and precision of studies) could only be performed on a proportion of the studies and outcomes.
In three of the seven studies reporting physical functioning as an outcome, and in three of the four studies reporting HRQOL, we identified a discrepancy between the author-reported results and the results we generated in the meta-analysis. In some studies, we reported a significant effect size derived from the random effects model when the individual study had reported equivocal findings. This may be due to the model awarding relatively more weight to smaller studies thus effectively increasing the power to detect significant changes in key outcomes in individual studies.22 Conversely, we found an equivocal outcome when the study had reported a significant improvement39; a lack of assessor blinding may have contributed to detection bias and an exaggeration in effect size. However, as vote counting takes into account the only the direction of effect and not the size of effect, the results of the meta-analyses are considered to be superior.22 The meta-analyses provide support for exercise as an effective intervention for improving physical functioning and HRQOL for people with PD, but the generalizability of these positive meta-analysis results should be interpreted with some caution.
We have found exercise to be effective at improving physical functioning and HRQOL, leg strength, balance, and walking but there is currently insufficient evidence with regards effectiveness in the areas of falls prevention and the management of depression. Future research needs to establish what elements constitute an optimal exercise intervention for people with PD such as the dosage, component parts of intervention, and the targeted stage of the disease. This is of particular importance given the deteriorating nature of this condition. In addition, researchers need to provide a theory driven rationale for the development of their intervention, ensure studies are adequately powered with a sample size sufficient to be able to detect a statistically significant difference, and report their findings, in accordance with currently internationally agreed standards such as CONSORT.47 It is also important that study populations reflect the general PD population in terms of gender and ethnicity in order to support the generalizability of findings.