Date: October 2016
Authors: Tanya Simuni, MD, Connie Marras, MD, PhD, and Terry Ellis, PhD, PT, NCS
Blog Editors: Michael S. Okun, MD, and Stella M. Papa, MD
Current pharmacological management is incompletely effective at controlling the symptoms of Parkinson’s disease and patients are often seeking complementary approaches. Exercise is a compelling strategy since recent evidence suggests both physical and cognitive benefits and, relative to many pharmacological therapies, it is inexpensive.
Prof. Connie Marras: We asked Prof. Terry Ellis, physical therapist and scientist at Boston University in Boston, MA, USA and Dr. Tanya Simuni, movement disorder neurologist and clinical researcher at Northwestern University in Chicago, IL, USA to discuss the current evidence for incorporating physical therapy and exercise into routine patient management, the gaps in our knowledge and the steps needed to clarify their role.
Prof. Terry Ellis: There are a growing number of randomized controlled trials and meta-analytic studies supporting the benefits of physical therapy and exercise in the treatment of Parkinson’s disease. Although many of the early exercise trials in PD lacked sufficient quality, had small sample sizes and were short-term (6-12 weeks) in nature, more recent exercise trials employ more rigorous methodologies, have larger sample sizes and are longer term (6-24 months) – providing more robust evidence in support of exercise. The International Parkinson and Movement Disorder Society Evidence Based Medicine Review Update concluded that physical therapy is likely efficacious – combined with pharmacological management – in the treatment of motor symptoms of PD. Although much progress has been made, questions remain. For example, despite the excitement surrounding the evidence for the neuroprotective and neurorestorative effects of exercise in animal models of PD, there are few studies examining the mechanisms underlying the effects of exercise on the human PD brain. The “best” form and “optimal” dose of exercise have also yet to be determined.
Despite the gaps in knowledge, the evidence supports incorporating exercise into the clinical management of PD. For example, the significant benefits of aerobic training, progressive resistance exercise and balance training in persons with PD have been demonstrated with few adverse events. Given the potential of exercise induced neuroplasticity, starting exercise as early as possible in the course of the disease is recommended. This should include early referral to physical therapy for the prescription of an evidence-based exercise program. It is also well-known that engagement in exercise must be ongoing – over the long-term – in order to optimize benefits. Just like with pharmacological treatment, if exercise is discontinued, the benefits will dissipate. Effective approaches to facilitate the adoption of exercise into daily life among those with PD are needed.
Dr. Tanya Simuni - Physical Therapy & Exercise in the Clinical Management of Parkinson Disease: Evidence and Practice:
It is absolutely true that over the last 15 years exercise has become an obligatory part of the comprehensive management of people with Parkinson’s disease. The number of publications on exercise studies has increased by a factor of 10 since 2000. From the clinical management standpoint there is sufficient evidence to advise the patients to get involved in a structured exercise program that includes a combination of aerobic, endurance and balance activities. Data from a large cohort of patients followed by the National Parkinson Foundation Centers of Excellence support the “common sense” notion that it is never too late to start exercising and that the intensity of exercise makes a difference.
However, from the scientific standpoint, if we want to approach exercise therapy with the same rigor as pharmacological and surgical management of PD, a number of questions remain unanswered including what are the optimal dose, frequency, intensity, and modality. These questions are routinely addressed in Phase 2 studies in drug development. Studies addressing these questions are ongoing; however, it is unlikely that one prescription would ever “ fit all." The most scientifically stimulating and challenging question to address is whether benefit of exercise is limited to maximizing compensatory mechanisms or does it truly have neuromodulating and neuroprotective effects. Designing studies to address the latter question (Phase 3) will be challenging, expensive and premature until the dose, frequency and modality questions are addressed in Phase 2 protocols.
In the interim, patient advocacy organizations should lobby for increased coverage for early physical therapy as a way to educate the PD community on the proper exercise modalities. Meanwhile, experts in patient centered outcomes research should develop studies focused on increasing exercise compliance potentially utilizing “smart technology" of ambulatory monitoring systems and wearable devices.
I would like to get Dr. Ellis' expert input on the next steps necessary in preparation for the pivotal studies of exercise as disease modifying intervention in Parkinson’s disease.
Prof. Terry Ellis: It remains unclear if one type of exercise is better than another or whether the intensity of the exercise matters in PD. Based on the results of exercise trials in PD thus far, it seems there is a specificity of training effect. In other words, aerobic exercise results in the greatest gains in cardiorespiratory function while progressive resistance exercise leads to the greatest improvements in strength and balance exercises contribute to the greatest gains in postural control. So, in some respects, there is no optimal exercise or “one size fits all” approach – the appropriate exercise prescription depends on the desired outcome.
However, if the goal is disease modification, one could argue that we need to identify which form of exercise has the greatest impact on reducing PD motor symptoms – analogous to the approach taken in pharmacological studies. Aerobic exercise, progressive resistance exercises and balance training have all been shown to reduce disease severity as measured by the MDS-UPDRS motor score. Should we compare them? Combine them? There is merit to both approaches. In terms of dose, there are mixed results with some studies pointing to the importance of high intensity exercise while others revealing equivalent improvements at a lower intensity. The SPARX trial, an ongoing multicenter, phase II trial in de novo patients with PD, is examining the feasibility of moderate and high intensity aerobic exercise and the impact on UPDRS motor scores. This dose-response intervention study will inform the development of a phase III trial. Similar approaches to determine optimal dosing of progressive resistance training and balance training are warranted. Other pivotal studies that should be done include ones that identify behavioral strategies to optimize engagement in exercise over the long-term in persons with PD. Effective strategies could then be incorporated into long-term phase III clinical exercise trials.
Dr. Tanya Simuni: Exercise has become an integral part of the comprehensive management of people with Parkinson’s disease. While a number of knowledge gaps remain and have to be addressed in future studies, there is sufficient evidence to support immediate benefits of exercise for clinicians to advocate regular physical activity. Patient advocacy organizations should continue to lobby for resources necessary to offer structured programs geared to different levels of abilities of people with PD.