Circadian Rhythms and Sleep-Wake Cycles in Parkinson's Disease

帕金森病的昼夜节律和睡眠-觉醒周期

• 批准号: 8299875
• 负责人: Aleksandar Videnovic
• 金额: $ 16.93万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8299875
• 关键词: Accidents; Activity Cycles; Adverse effects; Affect; Age; Animal Model; Area; Award; Basic Science; Behavioral; Biological Markers; Biological Rhythm; Biology; Caregivers; Chicago; Chronic; Circadian Rhythms; Clinical; Clinical Research; Corpus striatum structure; Coupled; Data; Development; Dopamine; Drowsiness; Etiology; Excessive Daytime Sleepiness; Exposure to; Fellowship; Foundations; Functional disorder; Gene Expression; Genes; Genetic; Goals; Health; Hour; Hypothalamic structure; Intervention; Knowledge; Lead; Light; Master' s Degree; Measures; Medicine; Melatonin; Mentored Patient-Oriented Research Career Development Award; Mentors; Moods; Morbidity - disease rate; Motor; Motor Activity; Movement Disorders; Nature; Neurodegenerative Disorders; Neurological outcome; Neurology; Output; Parkinson Disease; Participant; Patient Self-Report; Patients; Periodicity; Peripheral; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phototherapy; Physiological; Plasma; Play; Polysomnography; Population; Quality of life; Randomized; Recovery; Regulation; Research; Research Methodology; Research Personnel; Residencies; Rest; Role; Safety; Severity of illness; Sleep; Sleep Wake Cycle; Symptoms; System; Testing; Time; Training; Transcript; United States; Universities; actigraphy; alertness; base; career; circadian pacemaker; college; design; effective therapy; experience; hypnotic; improved; innovation; insight; interdisciplinary approach; mathematical model; molecular marker; mortality; novel; patient oriented; patient oriented research; post intervention; professor; programs; sedative; skills; sleep regulation; suprachiasmatic nucleus; treatment strategy

DESCRIPTION (provided by applicant): Disruption of sleep and alertness is one of the most disabling non-motor symptoms of Parkinson's disease (PD). Mechanisms leading to impaired sleep and alertness in PD are not well understood, and treatment options remain limited. This application for a K23 Mentored Patient-Oriented Research Career Development Award entitled "Circadian rhythms and sleep-wake cycles in Parkinson's Disease" is designed to provide Dr. Aleksandar Videnovic with the research skills and experience to bridge the areas of movement disorders, sleep and circadian biology in order to understand the basis for sleep and wake disturbances in PD. Dr. Videnovic is an Assistant Professor of Neurology at Northwestern University in Chicago. He completed residency training in Neurology at Northwestern University, a clinical fellowship in Movement Disorders at Rush University, and obtained a master's degree in clinical research from Rush Graduate College. Dr. Videnovic's long term career goal is to understand the role of circadian rhythms and sleep on neurological outcomes in movement disorders, and to utilize this knowledge to improve patients' health and quality of life by innovative circadian and sleep based strategies. His immediate goals are to gain knowledge and skills in circadian biology, sleep medicine, and clinical research methodology so as to investigate potential circadian rhythm abnormalities in PD. Dr. Videnovic has assembled a team of researchers who will mentor him during this award. His primary mentor, Dr. Phyllis Zee, and co-mentor Dr. Fred Turek are renowned investigators in the field of circadian biology with complementary expertise in patient oriented and basic science research. Expertise in mathematical modeling of circadian rhythms, statistical analyses, and clinical research in PD, will be provided by consultants, Drs. Elizabeth Klerman, Alfred Rademaker, and Tanya Simuni. The proposed training plan encompasses didactic and hands-on training on the characterization of the circadian system using physiological and molecular markers, assessments of the sleep-wake cycle, applications of circadian based treatments including light therapy, and further training in clinical research methods. The first part of the proposed research will examine the amplitude and stability of the circadian system using biological markers of the circadian system (e.g., melatonin, clock genes and the rest-activity cycle). The primary hypothesis is that disruption of circadian rhythmicity plays an important role in the development of poor sleep quality and daytime somnolence in PD. These markers of circadian rhythmicity will be correlated with sleep quality and degree of daytime somnolence in PD participants and healthy controls. The second part of the project is to test the hypothesis that increasing the strength and stability of circadian rhythms, using bright light exposure, will improve sleep quality and daytime somnolence in PD. Results from this research and the proposed training plan will form the foundation for an independent clinical research program at the interface of sleep, circadian biology and PD which may lead to novel and more effective treatments aimed to improve the health and quality of life of patients with PD. PUBLIC HEALTH RELEVANCE: Sleep dysfunction and excessive daytime somnolence are common and poorly understood symptoms of Parkinson 's disease (PD), affecting both patients and caregivers, and have a negative impact on the quality of life, safety, morbidity and mortality in the PD population. The proposed research is designed to provide new insight into a potential circadian rhythm etiology of sleep dysfunction in PD, form the foundation for novel circadian-based treatment strategies, and provide mentored training for the candidate as he continues to develop his career in patient-oriented research.

描述（由申请人提供）：睡眠和警觉性中断是帕金森病（PD）最具致残性的非运动症状之一。导致PD患者睡眠和警觉性受损的机制尚不清楚，治疗选择仍然有限。K23指导的以患者为导向的研究职业发展奖的申请题为“帕金森病的昼夜节律和睡眠-觉醒周期”，旨在为Aleksandar Vagovic博士提供研究技能和经验，以弥合运动障碍，睡眠和昼夜节律生物学领域，以了解PD中睡眠和觉醒障碍的基础。沃伊洛维奇博士是芝加哥西北大学神经病学助理教授。他在西北大学完成了神经病学的住院医师培训，在拉什大学获得了运动障碍的临床奖学金，并在拉什研究生院获得了临床研究硕士学位。Vagovic博士的长期职业目标是了解昼夜节律和睡眠对运动障碍神经系统结果的作用，并利用这些知识通过创新的昼夜节律和睡眠策略来改善患者的健康和生活质量。他的近期目标是获得昼夜节律生物学，睡眠医学和临床研究方法的知识和技能，以便调查PD中潜在的昼夜节律异常。Vagovic博士已经组建了一个研究团队，他们将在获奖期间指导他。他的主要导师Phyllis Zee博士和共同导师Fred Turek博士是昼夜节律生物学领域的著名研究人员，在以患者为导向的基础科学研究方面具有互补的专业知识。顾问Elizabeth Klerman、Alfred Rademaker和Tanya Simuni博士将提供昼夜节律数学建模、统计分析和PD临床研究方面的专业知识。拟议的培训计划包括使用生理和分子标志物表征昼夜节律系统的教学和实践培训，睡眠-觉醒周期的评估，基于昼夜节律的治疗（包括光疗）的应用，以及临床研究方法的进一步培训。所提出的研究的第一部分将使用昼夜节律系统的生物标志物（例如，褪黑激素、时钟基因和静息-活动周期）。主要假设是昼夜节律的破坏在PD患者睡眠质量差和日间嗜睡的发展中起重要作用。这些昼夜节律的标志物将与PD参与者和健康对照者的睡眠质量和日间嗜睡程度相关。项目的第二部分是验证增加强度和稳定性的假设 昼夜节律，使用明亮的光线照射，将改善睡眠质量和白天嗜睡的PD。这项研究的结果和拟议的培训计划将为睡眠，昼夜节律生物学和PD的独立临床研究计划奠定基础，这可能会导致旨在改善PD患者健康和生活质量的新的和更有效的治疗方法。 公共卫生相关性：睡眠功能障碍和白天过度嗜睡是帕金森病（PD）的常见症状，但人们对此知之甚少，影响患者和护理人员，并对PD人群的生活质量、安全性、发病率和死亡率产生负面影响。拟议的研究旨在为PD睡眠功能障碍的潜在昼夜节律病因提供新的见解，为新型基于昼夜节律的治疗策略奠定基础，并为候选人继续发展其职业生涯提供指导培训以患者为导向的研究。