Differentiation of Central versus Peripheral Fatigue in Parkinson's Disease

帕金森病中枢性疲劳与外周性疲劳的区别

• 批准号: 8366982
• 负责人: A. JOSEPH THRELKELD
• 金额: $ 36.1万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8366982
• 关键词: Affect; Age; Aging; American; Caregiver Burden; Caregivers; Development; Diagnosis; Dopa; Elderly; Evidence based intervention; Exercise; Fatigue; Generations; Goals; Incidence; Individual; Intervention; Isometric Exercise; Knee; Knee joint; Lead; Measurement; Measures; Mission; Movement; Muscle; Muscle Contraction; Neurodegenerative Disorders; Outcome; Outcome Measure; Parkinson Disease; Patients; Peripheral; Pharmaceutical Preparations; Population; Prevalence; Production; Protocols documentation; Public Health; Quality of life; Recovery; Rehabilitation therapy; Reporting; Rest; Role; Series; Societies; Source; Spinal; Symptoms; System; Torque; Treatment outcome; United States National Institutes of Health; Withdrawal; age related; base; hamstring; motor impairment; neuromuscular; quadriceps muscle; relating to nervous system; research study; response; sound; tool; young adult

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is a neurodegenerative disease characterized by impaired movement. One of the most common and disabling symptoms of PD is fatigability; fatigue that is induced by activity or exercise PD fatigability has deleterious effects on independence and quality of life in patients who have PD, as well as their caregivers. Despite these negative effects on patients and the increasing financial burden placed on society, few objective studies have investigated the underlying mechanisms of fatigability in PD. Specifically, we propose to define the roles of central mechanisms (cortical and spinal components) and peripheral mechanisms (muscular components) in PD fatigability. The long-term objective is to examine the neuromuscular mechanisms underlying fatigability by analyzing muscle activation and torque production obtained from people who have PD who report activity-related fatigability. To accomplish this goal, we will pursue the following specifi aims: ¿ Aim 1 is to differentiate between central and peripheral contributions to fatigability in people who have PD compared to age-matched and younger control subjects. ¿ Aim 2 is to evaluate the Dopa-responsiveness of PD-related fatigability. People who have PD, healthy young subjects, and age-matched control subjects will participate in the proposed study. Knee joint torque and electromyographic activities of the quadriceps and hamstrings will be measured during maximal isometric knee extension and flexion contractions. An isometric fatiguing protocol will be performed using the Biodex system. Superimposed electrical muscle stimulation will be used before and after the fatiguing protocol to determine central versus peripheral contributions to torque. Dopa-responsiveness of fatigue will be assessed by comparing the fatigability of each subject with PD on anti-PD medication (ON-med) with his or her fatigability after temporary withdrawal of medication (OFF-med). The study is intended to increase our understanding of the mechanisms underlying PD fatigability which will lead to better assessment tools to measure fatigability and the development of targeted, evidence-based interventions to relieve this disabling symptom of PD. PUBLIC HEALTH RELEVANCE: Parkinson's disease (PD) affects over 1.5 million Americans and is rapidly growing with 75,000 new cases diagnosed annually. PD is associated with motor impairments including rigidity and fatigue, which greatly diminish patients' quality of life. As th elderly population continues to expand, the prevalence of PD will continue to increase resulting in greater caregiver burden and financial demand. The proposed study is of significant relevance to public health and to the mission of NIH.

描述（由申请人提供）：帕金森病（PD）是一种以运动受损为特征的神经退行性疾病。PD最常见和致残的症状之一是疲劳;活动或运动引起的疲劳PD疲劳具有 对PD患者及其照顾者的独立性和生活质量的有害影响。尽管对患者有这些负面影响，并增加了社会的经济负担，但很少有客观的研究调查PD中疲劳的潜在机制。具体而言，我们建议定义的作用，中央机制（皮质和脊髓组件）和外周机制（肌肉组件）在PD疲劳。长期目标是通过分析从患有PD的报告活动相关疲劳的人获得的肌肉激活和扭矩产生来检查疲劳的神经肌肉机制。为了实现这一目标，我们将追求以下具体目标：目标1是区分与年龄匹配和年轻对照受试者相比，PD患者对疲劳的中枢和外周贡献。目标2是评估PD相关疲劳的多巴反应性。PD患者、健康年轻受试者和年龄匹配的对照受试者将参加拟定研究。将在最大等长膝关节伸展和屈曲收缩期间测量膝关节扭矩和股四头肌和腘绳肌的肌电图活动。将使用Biodex系统进行等长疲劳试验。在疲劳方案之前和之后将使用叠加电肌肉刺激，以确定中枢与外周对扭矩的贡献。将通过比较每例PD受试者接受抗PD药物治疗（ON-med）后的疲劳性与暂时停药后的疲劳性（OFF-med），评估疲劳的多巴反应性。该研究旨在增加我们对PD疲劳性潜在机制的理解，这将导致更好的评估工具来测量疲劳性，并开发有针对性的循证干预措施来缓解PD的这种致残症状。 帕金森病（PD）影响着超过150万美国人，并且正在迅速增长，每年诊断出75，000例新病例。PD与运动障碍相关，包括僵硬和疲劳，这大大降低了患者的生活质量。随着老年人口的持续增长，PD的患病率将继续增加，导致更大的护理负担和经济需求。这项研究对公共卫生和NIH的使命具有重要意义。