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：
9068250
负责人：
Aleksandar Videnovic
金额：
$ 19.35万
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/9068250
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 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 non-motor symptom 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）：睡眠和警觉性的破坏是帕金森氏病（PD）最残疾的非运动症状之一。尚不清楚导致睡眠不足和PD机敏性的机制，并且治疗方案仍然有限。该申请为K23指导的以患者为导向的研究职业发展奖，其标题为“昼夜节律的节奏和帕金森氏病中的睡眠效果周期”，旨在为Aleksandar Videnovic博士提供研究技能和经验，以弥合运动障碍，睡眠和昼夜节律生物学领域，以理解睡眠和唤醒的依据。 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的居住培训，在拉什大学（Rush University）的运动障碍临床研究金，并获得了Rush研究生学院的临床研究硕士学位。 Videnovic博士的长期职业目标是了解昼夜节律的作用并睡在运动障碍中的神经学成果上，并利用这些知识来改善创新的昼夜节律和基于睡眠的策略来改善患者的健康和生活质量。他的直接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，以研究PD中潜在的昼夜节律异常。 Videnovic博士召集了一组研究人员，他们将在此奖项中指导他。他的主要导师Phyllis Zee博士和弗雷德·图雷克（Fred Turek）博士是圆形生物学领域的著名研究人员，在面向患者和基础科学研究方面具有互补的专业知识。 PD的昼夜节律，统计分析和临床研究的数学建模专业知识将由顾问Drs提供。伊丽莎白·克勒曼（Elizabeth Klerman），阿尔弗雷德·拉德马克（Alfred Rademaker）和塔尼亚·西蒙尼（Tanya Simuni）。拟议的培训计划包括使用生理和分子标记物对昼夜节律进行表征的教学和动手培训，对睡眠效益周期的评估，基于昼夜节律治疗的应用，包括光治疗，以及在临床研究方法中的进一步培训。拟议的研究的第一部分将使用昼夜节律系统的生物学标记（例如褪黑激素，时钟基因和静止活性循环）检查昼夜节律系统的幅度和稳定性。主要的假设是，昼夜节律的破坏在PD的睡眠质量和白天迟感的发展中起着重要作用。这些昼夜节律的标志物将与PD参与者和健康对照组中的睡眠质量和白天的睡眠程度相关。该项目的第二部分是测试增加强度和稳定性的假设使用明亮的光线曝光，昼夜节律的节奏将改善PD的睡眠质量和白天的嗜睡。这项研究和拟议的培训计划的结果将为睡眠，昼夜节律生物学和PD界面的独立临床研究计划奠定基础，这可能会导致新颖，更有效的治疗方法，旨在改善PD患者的健康和生活质量。