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: 10663892
• 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/10663892
• 关键词: Acetylcholinesterase Inhibitors; 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; Immobilization; Impaired cognition; Impairment; Individual; Individual Differences; Infrastructure; Knowledge; Long-Term Effects; Measures; Mediating; Medical; Metabolic; Monitor; Mood Disorders; Motor; Movement; Nerve Degeneration; 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; VO2max; Veterans; Work; brain health; brain tissue; cardiorespiratory fitness; cognitive function; cost; disability; 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; neural; non-motor symptom; 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）以巨大的社会成本达到痴呆，固定和死亡的高潮。甚至很早 课程，运动和认知功能障碍会损害日常生活的器乐活动（IADL）。非运动器 由于疲劳，情绪，睡眠和自主障碍而引起的症状进一步降低了生活质量（QOL）。 DTI显示 脑组织完整性的逐步下降。通常对医学和外科治疗中心的PD护理 缓解运动症状，但随着时间的推移会导致副作用并失去疗效。通常治疗非 用药物（例如，抗抑郁药）的运动表现是有症状的，不是PD的特异性。 乙酰胆碱酯酶抑制剂对痴呆症具有适度的症状好处，但没有批准 治疗轻度认知障碍。在移动性时，通常在后期处方物理治疗 随之而来的障碍。 PD没有批准的标准运动方案。没有治愈或疾病 修改治疗。因此，对提供广泛利益和 慢pd。初步研究表明，有氧运动有潜力满足这一需求。然而， 有氧运动的要求很高，并带来一些风险。未知有氧运动是否比 由于我们对心肺健康影响（CRF）的影响，长期在PD中进行通常的护理 关于脑组织完整性，运动功能，认知，IADL，QOL和疾病进展。电流的局限性 研究包括持续时间短，样本量较小，控制不足或缺乏结果指标 认知和IADL，以及缺乏测量进展的生物标记。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，临床和功能效应来填补翻译空白 pd中的运动（LTAE）。我们的总体假设是LTAE改善了脑组织完整性并减慢 下降。我们的第一个目的是确定LTAE对PD临床特征和功能能力的影响。 我们之前的6个月不受控制的试验表明有氧运动改善了有氧运动的初步证据 PD中的运动功能，认知和QoL，但长期的结果和对功能能力的影响是 未知。我们假设LTAE将在运动功能，认知和非 - 运动症状，转化为QOL和IADL的好处。我们将通过一年的随机进行测试 对照试验（RCT）比较了中度有氧运动与通常的护理的影响。我们将使用驾驶 作为IADL的结果。驾驶代表了独立的重要符号，并取决于诚信 认知和运动系统。我们的第二个目的是确定PD中LTAE效应的机制。 CRF 反映了有氧运动中血管，心脏和代谢健康的复杂改善。有 初步证据表明，较高的CRF与更好的大脑健康和运动/认知功能有关，并且 有氧运动可以改善这些结果。例如，我们的初步研究表明 DTI上的纹状体和白质的微动物完整性，但尚不清楚这些变化如何抵消 长期PD进展。我们的假设是：1）LTAE将改善脑组织完整性，如 DTI，2）LTAE对运动和认知功能的影响是由DTI对脑组织完整性的变化所介导的， 3）导致AE CRF改善的生理过程对于脑组织的益处至关重要 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，以及与训练相关的运动变化和认知变化的个体差异之间的关联 功能，DTI和CRF。总而言之，我们的提议利用了我们多样化的跨学科团队 初步数据和过去的工作以及独特的基础架构，以确定LTAE是否会减慢神经变性 和PD的临床障碍。