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.

摘要

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

Relationships of self-reported and objective measures of sleep, sleepiness, and sleep quality in Parkinson's disease.

帕金森病患者睡眠、嗜睡和睡眠质量的自我报告和客观测量之间的关系。

• DOI: 10.1016/j.parkreldis.2022.06.009
• 发表时间: 2022
• 期刊: Parkinsonism & related disorders
• 影响因子: 4.1
• 作者: Stauder,Matthew;Klerman,ElizabethB;Wang,Wei;Erickson,Hans;Videnovic,Aleksandar
• 通讯作者: Videnovic,Aleksandar