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

描述(申请人提供)：对于帕金森氏症(PD)患者，震颤、僵硬、平衡不良和行走困难等症状往往限制他们参与体力活动。这种体力活动的减少会加速与衰老相关的运动控制能力的退化，从而导致功能能力的螺旋式下降，最终可能导致跌倒、丧失独立性和/或呼吸问题。帕金森病的药物治疗可以在早期缓解症状，但在疾病的晚期往往效果较差，而且往往会产生衰弱的副作用。此外，目前还没有可用的治疗方法来阻止或减缓帕金森病的进展。最近在动物身上的研究表明，运动训练可以通过增加神经发生、神经营养因子和神经元存活而导致有利的脑功能变化。一些人体研究间接支持了这一观点，观察到经常参加体力活动和心血管健康程度较高的人的认知功能和注意力都有所改善。基于这项研究和其他研究证据，这项努力的长期目标是开发和优化一种运动干预，以提高帕金森病患者的功能能力。这项探索性研究将试图确定，针对帕金森病患者的锻炼计划可以改善功能结果，并调查可能导致这种改善的大脑代谢变化。下一步工作将进一步 描述适应性大脑机制(神经发生、神经营养和/或逆转神经退行性变)，并优化运动干预。该项目的具体目标是：(1)建立并向一组帕金森病患者提供易于管理的运动治疗方案，(2)使用一系列功能结果测量(平衡、步态、僵直、震颤、心肺功能和认知任务表现)来评估潜在的益处，以及(3)使用FDG PET成像来研究可能支持这些益处的大脑代谢变化。16名帕金森病患者将参加为期12周的骑马(用扁担走路)锻炼计划。虽然所有受试者都将接受功能改善的评估，但只会从总共16名受试者中随机挑选8名受试者来评估大脑新陈代谢的变化。受试者将在基线(干预前12周)、干预前、干预后和随访(运动干预完成后12周)定期接受一系列测试。 这项研究将提供一种易于实施的干预措施，可以为帕金森病患者带来临床益处。此外，这项关于帕金森病后运动诱导的脑代谢变化的初步调查将为后续研究奠定基础，以探索和优化运动干预措施，以促进大脑对帕金森病治疗的适应。公共卫生相关性：在美国，65岁以上的人中有近1%被诊断为帕金森病，患病率为每10万人中有128至187人，年发病率为每10万人中有20人。最近，有研究表明，长期的运动训练可以显著减缓帕金森病患者的神经退变过程和/或促进神经适应，这可以显著改善功能能力，增加独立性，并降低医疗费用。如果拟议的马术运动训练可以在功能结果方面产生预期的改善和大脑功能的有利变化，那么可以将马术训练作为一种非药物疗法来开发，以缓解帕金森病的症状，抵消与衰老相关的运动能力下降，并有可能减缓或逆转疾病的进展。

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.