Bright light modulation of non-motor symptoms in Parkinson's disease

帕金森病非运动症状的亮光调节

• 批准号: 10054198
• 负责人: Aleksandar Videnovic
• 金额: $ 55.07万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054198
• 关键词: ARNTL gene; Activity Cycles; Address; Affect; Area; Biological Rhythm; Brain; Chronic; Circadian Dysregulation; Circadian Rhythms; Clinical; Clinical Research; Clinical Trials; Consensus; Coupled; Development; Diagnosis; Disease; Dopa; Drowsiness; Etiology; Foundations; Functional disorder; Future; Gene Expression; Genes; Goals; Hormonal; Hour; Human; Hypothalamic structure; Impairment; Individual; Inpatients; Intervention; Life; Light; Measures; Medical; Medicine; Melatonin; Morbidity - disease rate; Movement Disorder Society Unified Parkinson' s Disease Rating Scale; National Institute of Neurological Disorders and Stroke; Nature; Neurodegenerative Disorders; Outcome; Outcome Measure; Parkinson Disease; Participant; Patient Self-Report; Patients; Pattern; Phase; Phototherapy; Pilot Projects; Polysomnography; Population; Prevention; Psyche structure; Quality of life; Questionnaires; Randomized; Recommendation; Records; Reporting; Research; Research Design; Resistance; Rest; Role; Severities; Signal Transduction; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; System; Testing; United States National Institutes of Health; Visual; Work; actigraphy; alertness; analog; associated symptom; base; circadian; cohort; diaries; effective therapy; experience; improved; improved functioning; insight; light effects; meetings; molecular marker; mortality; non-motor symptom; novel; poor sleep; sleep regulation; suprachiasmatic nucleus; therapeutic target; therapy outcome

Abstract Non-motor symptoms (NMS) are some of the most disabling manifestations of Parkinson’s disease (PD). Disrupted sleep and alertness are among the most common NMS. Mechanisms leading to NMS are not well understood and treatment options remain limited. The endogenous human circadian system has a critical role in the regulation of sleep-wake cycles and is mostly effectively synchronized by environmental light. The circadian system has not been systematically studied in the PD population. Our pilot studies in patients with PD revealed: (i) blunting of circadian rhythm of melatonin, a well established marker of circadian rhythms; (ii) changes in circadian timing (“phase”) of clock gene expression; and (iii) beneficial effects of bright light therapy (LT) on sleep-wake consolidation. This project aims to examine effects of LT on NMS with an emphasis on sleep, alertness, and circadian markers in a cohort of 54 PD participants with poor sleep over 14 weeks. Study participants will be randomized to either bright white LT or dim-red LT (control) condition. Participants will have inpatient assessments for circadian markers and sleep using polysomnography (PSG) before and after LT. Throughout the study, participants will wear an actigraph for continuous monitoring of sleep-wake patterns, keep daily sleep diaries and records of LT exposure, and complete visual analog scales (VAS) for alertness level. Questionnaires to assess sleep, alertness, and NMS will be performed at baseline, following 8 weeks of LT, and at the end of the study. Aim 1 will determine effects of LT on self-reported (Parkinson’s Disease Sleep Scale 2 and sleep diaries) and objective (PSG, actigraphy) measures of sleep. Aim 2 will determine effects of LT on circadian markers, specifically amplitude and phase of melatonin and clock genes Bmal1, Per1,2, and 3, as well as inter- daily stability of the rest-activity cycles (actigraphy). Aim 3 will determine effects of LT on alertness (Epworth Sleepiness Scale and VAS alertness scale). Aim 4 will determine effects of LT on NMS burden (The Non Motor Symptoms Assessment Scale for PD and Part I of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale). The study design will quantify within each individual the relationships of LT, objective and subjective sleep, circadian markers, alertness, and NMS burden. Long-term, this project addresses the need to improve our understanding of the pathophysiology of NMS in PD and develop novel treatments. Short- term, the project will provide a foundation for a future clinical trial of LT through testing of a potential target (the circadian system), therapy (LT) and outcome measures in the PD population. This project is responsive to several highest priority areas for clinical research outlined in the most recent NINDS PD Research Consensus Meeting, and in the NIH Sleep Disorders Research Plan: (i) to develop effective treatments for non-motor features of PD; (ii) to advance the understanding of sleep and circadian functions in both the brain and body; and (iii) to improve prevention, diagnosis, and treatment of sleep and circadian disorders.

抽象的 非运动症状（NMS）是帕金森氏病（PD）最残疾的表现。 睡眠和机敏性破坏是最常见的NM。导致NM的机制不好 理解和治疗方案仍然有限。内源性人类昼夜节律系统至关重要 在调节睡眠效果周期中，大多数通过环境光有效地同步。 在PD人群中尚未系统地研究昼夜节律系统。我们对患者的试点研究 PD透露：（i）淡化褪黑激素的昼夜节律，这是昼夜节律的良好标志； （ii） 时钟基因表达的昼夜节律时间（“相”）的变化； （iii）明亮光治疗的有益影响 （lt）睡眠觉醒合并。 该项目旨在检查LT对NM的影响，重点是睡眠，机敏和昼夜节律 在14周内睡眠不足的54名PD参与者队列中的标记。学习参与者将被随机分配 到明亮的白色LT或昏暗的LT（控制）条件。参与者将对 LT之前和之后使用多聚术（PSG）（PSG）的昼夜节律标记和睡眠。在整个研究中， 参与者将佩戴行动式图片，以连续监控睡眠效果图案，保持日记每日睡眠日记 LT暴露的记录，以及完整的视觉模拟量表（VAS）以达到警报水平。问卷 评估睡眠，机敏性和NMS将在LT 8周后在基线上进行。 学习。 AIM 1将确定LT对自我报告的影响（帕金森氏病睡眠量表2和睡眠 日记）和客观（PSG，行动摄影）的睡眠度量。 AIM 2将确定LT对昼夜节律的影响 标记物，特别是褪黑激素和时钟基因BMAL1，Per1,2和3的标记物以及相互间 静止循环的每日稳定性（行动学）。 AIM 3将确定LT对警报的影响（Epworth 嗜睡量表和VAS警报量表。 AIM 4将确定LT对NMS Burnen的影响（非电动机 PD的症状评估量表和运动障碍社会的第一部分 疾病评级量表）。研究设计将在每个人中量化LT的关系 和主观睡眠，昼夜节标记，机敏和NMS负担。长期，该项目解决了 需要提高我们对PD中NMS的病理生理学的理解，并开发新的治疗方法。短的- 术语，该项目将通过测试潜在目标为LT的未来临床试验提供基础（ PD人群中的昼夜节律系统，治疗（LT）和结果度量。这个项目对 最新的NINDS PD研究共识中概述的临床研究的几个最高优先级领域 会议和NIH睡眠障碍研究计划：（i）开发有效的非运动治疗方法 PD的功能； （ii）促进对大脑和身体的昼夜节律功能的理解； （iii）改善睡眠和昼夜节律疾病的预防，诊断和治疗。

项目成果

Chronotype, sleep, and sleepiness in Parkinson's disease.

帕金森病的睡眠时间型、睡眠和嗜睡。

• DOI: 10.1016/j.parkreldis.2022.10.011
• 发表时间: 2023
• 期刊: Parkinsonism & related disorders
• 影响因子: 4.1
• 作者: Murphy,Samantha;Chibnik,LoriB;Videnovic,Aleksandar
• 通讯作者: Videnovic,Aleksandar

SLEEP AND CIRCADIAN RHYTHM DISORDERS IN PARKINSON'S DISEASE.

• DOI: 10.1007/s40675-017-0079-y
• 发表时间: 2017-09
• 期刊: Current sleep medicine reports
• 影响因子: 1.8
• 作者: Gros P;Videnovic A
• 通讯作者: Videnovic A

Management of sleep disorders in Parkinson's disease and multiple system atrophy.

• DOI: 10.1002/mds.26918
• 发表时间: 2017-05
• 期刊: Movement disorders : official journal of the Movement Disorder Society
• 作者: Videnovic A

Light Therapy in Parkinson's Disease: Towards Mechanism-Based Protocols.

• DOI: 10.1016/j.tins.2018.03.002
• 发表时间: 2018-05
• 期刊: Trends in neurosciences
• 影响因子: 15.9
• 作者: Fifel K;Videnovic A
• 通讯作者: Videnovic A

Clinical trials in REM sleep behavioural disorder: challenges and opportunities.

• DOI: 10.1136/jnnp-2020-322875
• 发表时间: 2020-07
• 期刊: Journal of neurology, neurosurgery, and psychiatry
• 作者: Videnovic A;Ju YS;Arnulf I;Cochen-De Cock V;Högl B;Kunz D;Provini F;Ratti PL;Schiess MC;Schenck CH;Trenkwalder C;Treatment and Trials Working Group of the International RBD Study Group
• 通讯作者: Treatment and Trials Working Group of the International RBD Study Group