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

基本信息

批准号：
8730404
负责人：
Aleksandar Videnovic
金额：
$ 16.2万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
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/8730404
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&apos 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 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 motor function recovery novel patient oriented patient oriented research post intervention professor programs sedative skills sleep regulation suprachiasmatic nucleus treatment strategy

项目摘要

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.

描述（由申请人提供）：睡眠和警觉性中断是帕金森病 (PD) 最严重的非运动症状之一。帕金森病导致睡眠和警觉性受损的机制尚不清楚，治疗选择仍然有限。本次申请题为“帕金森病的昼夜节律和睡眠-觉醒周期”的 K23 指导患者导向研究职业发展奖，旨在为 Aleksandar Videnovic 博士提供研究技能和经验，以弥合运动障碍、睡眠和睡眠障碍等领域。昼夜节律生物学，以了解帕金森病睡眠和觉醒障碍的基础。 Videnovic 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住院医师培训，在拉什大学完成了运动障碍临床研究员培训，并在拉什研究生院获得了临床研究硕士学位。 Videnovic 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方面的知识和技能，以研究帕金森病中潜在的昼夜节律异常。维德诺维奇博士组建了一个研究团队，他们将在获奖期间为他提供指导。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拥有互补的专业知识。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将由顾问、博士提供。伊丽莎白·克勒曼、阿尔弗雷德·雷德梅克和坦尼娅·西穆尼。拟议的培训计划包括关于使用生理和分子标记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（包括光疗法）的应用以及临床研究方法的进一步培训。拟议研究的第一部分将利用昼夜节律系统的生物标记（例如褪黑激素、时钟基因和休息-活动周期）来检查昼夜节律系统的幅度和稳定性。主要假设是昼夜节律的破坏在帕金森病患者睡眠质量差和白天嗜睡的发生中起着重要作用。这些昼夜节律标记将与 PD 参与者和健康对照组的睡眠质量和白天嗜睡程度相关。该项目的第二部分是检验增加强度和稳定性的假设使用强光照射来改变昼夜节律将改善帕金森病患者的睡眠质量和白天嗜睡。这项研究的结果和拟议的培训计划将为睡眠、昼夜节律生物学和帕金森病之间的独立临床研究项目奠定基础，这可能会带来新颖、更有效的治疗方法，旨在改善患有帕金森病的患者的健康和生活质量。 PD。