Long Term Aerobic Exercise to Slow Progression in Parkinson's Disease

长期有氧运动可减缓帕金森病的进展

• 批准号: 10490257
• 负责人: ERGUN Y UC
• 金额: --
• 依托单位: IOWA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490257
• 关键词: Acetylcholine; Activities of Daily Living; Adverse event; Aerobic; Aerobic Exercise; Aging; American; Animals; Antidepressive Agents; Automobile Driving; Autonomic nervous system disorders; Biological; Biological Markers; Blood Vessels; Brain; Cardiac; Cessation of life; Clinical; Clinical Trials; Cognition; Cognitive; Complex; Corpus striatum structure; Data; Dementia; Disease; Disease Progression; Fatigue; Health; Human; Impaired cognition; Impairment; Individual; Individual Differences; Infrastructure; Knowledge; Long-Term Effects; Measures; Mediating; Medical; Metabolic; Monitor; Mood Disorders; Motor; Movement; Nerve Degeneration; Neuronal Plasticity; Operative Surgical Procedures; Outcome; Outcome Measure; Parkinson Disease; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Physical therapy; Physiological Processes; Quality of life; Randomized Controlled Trials; Research; Research Design; Risk; Sample Size; Sleep Disorders; Structure; Symptoms; System; Testing; Time; Tissues; Training; Translations; Uncontrolled Study; VO2max; Veterans; Work; brain health; brain tissue; cardiorespiratory fitness; cognitive function; cost; disability; esterase inhibitor; exercise regimen; functional outcomes; improved; improved outcome; indexing; instrumental activity of daily living; mental function; mild cognitive impairment; motor disorder; motor function improvement; motor impairment; motor symptom; non-motor symptom; relating to nervous system; side effect; societal costs; treatment as usual; trial comparing; white matter

Parkinson's disease (PD) culminates in dementia, immobility, and death at a huge societal cost. Even early in the course, motor and cognitive dysfunction impairs instrumental activities of daily living (IADL). Non-motor symptoms due to fatigue, mood, sleep, and autonomic disorders further reduce quality of life (QoL). DTI shows progressive decline in brain tissue integrity. Usual care of PD centers on medical and surgical treatments relieve motor symptoms, but these cause side effects and lose efficacy over time. Usual treatment for non- motor manifestations with pharmaceuticals (e.g., antidepressants) is symptomatic and not specific for PD. Acetylcholine esterase inhibitors exert modest symptomatic benefits on dementia, but there is no approved treatment for mild cognitive impairment. Physical Therapy is usually prescribed in later stages when mobility impairment ensues. There is no approved standard exercise regimen for PD. There is no cure or disease modifying treatment. Thus, there is a critical need for treatments that provide broad spectrum of benefits and slow PD. Preliminary research suggests that aerobic exercise has potential to meet this need. However, aerobic exercise is demanding and carries some risks. It is unknown if aerobic exercise is more beneficial than usual care in PD in long term due to gaps in our knowledge about the effects of cardiorespiratory fitness (CRF) on brain tissue integrity, motor function, cognition, IADL, QoL, and disease progression. Limitations of current studies include short duration, small sample size, lack or inadequacy of controls, lack of outcome measures for cognition and IADL, and lack of biological markers to measure progression. Our objective in this application is to fill the translational gap by determining the biological, clinical, and functional effects of long term aerobic exercise (LTAE) in PD. Our overall hypothesis is that LTAE improves brain tissue integrity and slows down PD. Our FIRST AIM is to determine the effects of LTAE on clinical features and functional abilities in PD. Our prior 6-month, uncontrolled trial showed preliminary evidence that aerobic exercise improves aspects of motor function, cognition, and QoL in PD, but long term outcomes and implication for functional abilities are unknown. We hypothesize that LTAE will provide sustained improvement in motor function, cognition, and non- motor symptoms with translation of benefits to QoL and IADL. We will test this with a one-year randomized controlled trial (RCT) that compares the effects of moderate aerobic exercise vs usual care. We will use driving as the outcome for IADL. Driving represents an important symbol for independence, and depends on integrity of cognitive and motor systems. Our SECOND AIM is to determine the mechanism of LTAE effects in PD. CRF reflects complex improvements in vascular, cardiac, and metabolic health from aerobic exercise. There is preliminary evidence that higher CRF is associated with better brain health and motor/cognitive function, and that aerobic exercise improves these outcomes. For example, our preliminary study showed improvement of microtissue integrity in the striatum and white matter on DTI, but it is unclear how these changes counteract PD progression over long term. Our hypotheses are: 1) LTAE will improve brain tissue integrity as indexed by DTI, 2) LTAE effects on motor and cognitive function are mediated by changes in brain tissue integrity on DTI, and 3) physiological processes leading to improved CRF from AE are critical to the benefits on the brain tissue integrity and motor/cognitive function. We will test these hypotheses determining the effects of LTAE on CRF and DTI, and the association between individual differences in training-related changes in motor and cognitive function, DTI, and CRF. In summary, our proposal leverages our diverse interdisciplinary team, strong preliminary data and past work, and unique infrastructure to determine if LTAE slows down neurodegeneration and clinical disability in PD.

帕金森氏病(PD)最终导致痴呆、行动不便和死亡，造成巨大的社会成本。即使是在早期 运动和认知功能障碍损害日常生活的工具性活动(IADL)。非马达 疲劳、情绪、睡眠和自主神经障碍引起的症状进一步降低了生活质量。DTI节目 脑组织完整性进行性下降。帕金森病的常规护理以内科和外科治疗为中心 缓解运动症状，但这些会引起副作用，并随着时间的推移而失效。非霍奇金患者的常规治疗 药物(如抗抑郁药)的运动表现是有症状的，对帕金森病没有特异性。 乙酰胆碱酯酶抑制剂对痴呆症有适度的症状缓解作用，但尚无批准 轻度认知障碍的治疗。物理治疗通常是在活动的后期阶段进行的 随之而来的是损害。目前还没有批准的帕金森病标准锻炼方案。没有治愈方法，也没有疾病 修改治疗方法。因此，迫切需要一种提供广泛益处和 慢吞吞的警察。初步研究表明，有氧运动有潜力满足这一需求。然而， 有氧运动要求很高，也有一定的风险。有氧运动是否比有氧运动更有益还不得而知 由于我们对心肺适能(CRF)的影响认识不足，帕金森病患者的长期常规护理 对脑组织完整性、运动功能、认知、IADL、生活质量和疾病进展的影响。电流的限制 研究包括持续时间短、样本量小、缺乏或不充分对照、缺乏结果衡量标准 认知和IADL，以及缺乏衡量进步的生物标记物。我们在此应用程序中的目标是 通过确定长期有氧运动的生物学、临床和功能影响来填补翻译空白 帕金森病患者运动(LTAE)。我们的总体假设是LTAE改善了脑组织的完整性，并减缓了 下了警局。我们的首要目标是确定LTAE对帕金森病患者临床特征和功能的影响。 我们之前为期6个月的非对照试验显示，初步证据表明，有氧运动可以改善 帕金森病患者的运动功能、认知和生活质量，但长期结果和对功能能力的影响 未知。我们假设LTAE将提供持续的运动功能、认知和非 运动症状，转化为QOL和IADL的益处。我们将通过为期一年的随机试验来测试这一点 对照试验(RCT)，比较中等有氧运动和常规护理的效果。我们将使用驾驶 作为IADL的结果。驾驶是独立的重要标志，它依赖于正直 认知和运动系统。我们的第二个目标是确定LTAE在帕金森病中的作用机制。CRF 反映了有氧运动对血管、心脏和代谢健康的复杂改善。的确有 初步证据表明，较高的CRF与更好的大脑健康和运动/认知功能相关，以及 有氧运动可以改善这些结果。例如，我们的初步研究显示， DTI上纹状体和白质的微组织完整性，但尚不清楚这些变化是如何抵消的 帕金森病长期进展。我们的假设是：1)LTAE将改善脑组织的完整性，由 DTI对运动和认知功能的影响是通过DTI对脑组织完整性的改变而实现的。 3)导致AE改善CRF的生理过程是对脑组织有益的关键 完整性和运动/认知功能。我们将测试这些假设，以确定LTAE对CRF的影响 和DTI，以及训练相关运动和认知变化的个体差异之间的联系 函数、DTI和CRF。总而言之，我们的计划利用了我们多样化的跨学科团队，Strong 初步数据和过去的工作，以及确定LTAE是否减缓神经变性的独特基础设施 和帕金森病患者的临床残疾。