Exercise training in Parkinson's disease: Neural and functional benefits

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DESCRIPTION (provided by applicant): For individuals with Parkinson's disease (PD), symptoms such as tremor, rigidity, poor balance and difficulties in walking often limit their participation in physical activities. Such reductions in physical activity can accelerate aging-related degradations in motor control and therefore contribute to a spiraling decline in functional capacity that may eventually result in falls, loss of independence and or respiratory problems. Pharmacological treatment of PD can provide symptomatic relief during the early years, but is often less effective in the advanced stages of the disease and can often produce debilitating side effects. Moreover, there are no treatments currently available to stop or slow the progression of PD. Recent studies in animals have demonstrated that exercise training can result in favorable changes in brain function by increasing neurogenesis, neurotrophic factors and neuronal survival. Some human studies have indirectly supported this notion with observations of improved cognitive function and attention in people who participate in regular physical activity and who have higher cardiovascular fitness. Based on this and other research evidence, the long-term goal of this effort is to develop and optimize an exercise intervention that improves functional capacity in PD. This exploratory study will seek to establish that an exercise program for individuals with PD can provide improvements in functional outcomes and to investigate the changes in brain metabolism that may underlie such improvements. Future work will further characterize the adaptive brain mechanisms (neurogenesis, neurotrophism, and/or reversal of neurodegeneration) and optimize the exercise intervention. The specific aims of this project are: (1) to establish and deliver a readily-administered exercise therapy protocol to a group of individuals with PD, (2) to assess potential benefits using a battery of functional outcomes measures (balance, gait, rigidity, tremor, cardiorespiratory function, and cognitive task performance), and (3) to investigate the brain metabolic changes using FDG PET imaging that may underlie such benefits. Sixteen people with PD will participate in a 12-week polestriding (walking with poles) exercise program. While all the subjects will be evaluated for functional improvements, the changes in the brain metabolism will be evaluated only in eight subjects who will be randomly selected from a total of sixteen subjects. Subjects will undergo a battery of tests periodically at baseline (12 weeks prior to the intervention), pre-intervention, postintervention, and follow-up (12 weeks after completion of the exercise intervention). This study will provide a readily-administered intervention that can produce clinical benefits for individuals with PD. Furthermore, this initial investigation of exercise-induced changes in brain metabolism after PD will lay the foundation for follow-up studies to investigate and optimize exercise interventions to promote adaptation in the brain for treatment of PD. PUBLIC HEALTH RELEVANCE: Nearly 1% of people older than 65 years have been diagnosed with PD with a prevalence of 128 to 187 per 100,000 and an annual incidence of 20 per 100,000 in the United States. Recently, it has been suggested that long-term exercise training may substantially slow the neurodegenerative process and/or promote neuroadaptation in individuals with PD, which could significantly improve functional capabilities, increase independence, and reduce health care costs. If the proposed polestriding exercise training can result in anticipated improvements in functional outcomes and favorable changes in brain function, then regular practice of polestriding can be developed as a non-pharmacological therapy to alleviate symptoms of PD, to offset the aging-related decline in motor capabilities, and potentially to slow or reverse the disease progression.