The Role of Palliative Care Interventions to Reduce Circadian Rhythm Disorders in Persons with Dementia

 描述(申请人提供)：超过500万美国人患有阿尔茨海默病或相关痴呆症，这是一种进行性和致命性的神经退行性疾病，影响到近1500万家庭照顾者(CG)。为了提高生活质量(QOL)和减轻症状负担，建议对痴呆症患者采取上游姑息护理模式。昼夜节律紊乱(CRD)发生在大多数痴呆症患者中，包括下午晚些时候/晚上的躁动和不规则的睡眠-觉醒节律，如日间过度睡眠、夜间频繁唤醒和睡眠效率低下。慢性阻塞性肺疾病的症状给慢性阻塞性肺疾病带来了巨大的负担，也是困扰、生活质量差和住院的主要原因。通过使用光和活动来调节昼夜节律系统已被证明可以改变驱动CRD症状的核心时钟过程，并表明在战略时刻进行基于认知、身体和感觉的活动的组合可能是减少CRD症状的有效机制。越来越多的研究支持以活动为基础的干预作为一种缓解方法的重要性，以减少CRD症状的频率和强度，增强人格和尊严，并改善生活质量。到目前为止，还没有试验将活动的性质和时机与关键的缓解和生物行为结果联系起来。我们建议对“健康模式”干预进行最终的第三阶段疗效试验，这是一种以家庭为基础的活动干预，旨在改善CRDS和生活质量，建立在我们试点工作的基础上。我们将采用随机两组平行设计，将200名痴呆症患者和他们的CG(DYAD)分配到“健康模式”干预或同等家庭关注和社交接触的对照干预中。干预的具体组成部分包括：1)评估健康/功能状况和偏好/兴趣；2)教育CG关于环境线索以促进活动和睡眠；以及3)培训CG根据昼夜需要使用定时的上午、下午和晚上的活动。干预的成功将取决于它对姑息结果的影响，包括生活质量的测量，以及CRD症状的活动和代理报告的测量。关注的CG结果将是负担、主观睡眠质量和生活质量。我们还将通过唾液皮质醇和暗光褪黑素测量每日神经内分泌活性来检验干预对CRD症状的作用机制。拟议研究的结果将提供关于基于昼夜节律需求的活动参与的性质和时间的基本新知识，以及可能改变为痴呆症患者提供活动的方式和时间的潜在的定时活动的机制。

 DESCRIPTION (provided by applicant): Over 5 million Americans have Alzheimer's disease or a related dementia, a progressive and fatal neurodegenerative condition, affecting close to 15 million family caregivers (CG). A palliative model of care is advocated "upstream" for persons with dementia in order to enhance quality of life (QOL) and reduce symptom burden. Circadian rhythm disorders (CRD's) occur in the majority of persons with dementia and include late afternoon/evening agitation and irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, and poor sleep efficiency. CRD symptoms pose a great burden to CG, and are the principal causes of distress, poor QOL, and institutionalization. Regulating the circadian system through the use of light and activity has been shown to alter core clock processes that drive CRD symptoms and suggests that a combination of cognitive, physical and sensory-based activities, delivered at strategic times, may be an effective mechanism through which to reduce CRD symptoms. A growing body of research supports the importance of activity-based interventions as a palliative approach to reduce the frequency and intensity of CRD symptoms, enhance personhood and dignity, and improve QOL. To date, there are no trials linking the nature and timing of activities with key palliative and biobehavioral outcomes. We propose a definitive Phase III efficacy trial of the "Healthy Patterns" intervention, a home-based activity intervention designed to improve CRDs and QOL that builds on our pilot work. We will use a randomized two-group parallel design of 200 people with dementia and their CGs (dyads) assigned to the "Healthy Patterns" intervention or a control intervention of equivalent in-home attention and social contact. Specific components of the intervention include: 1) assessing health/functional status and preferences/interests; 2) educating CG on environmental cues to promote activity and sleep; and 3) training of CG in using timed morning, afternoon, and evening activities based on circadian needs. The success of the intervention will be determined by its impact on palliative outcomes including measures of QOL as well as actigraphic and proxy reported measures of CRD symptoms. CG outcomes of interest will be burden, subjective sleep quality, and QOL. We will also examine the mechanism of action of the intervention on CRD symptoms through diurnal neuroendocrine activity measured via salivary cortisol and dim light melatonin. Results from the proposed study will provide fundamental new knowledge regarding the nature and timing of activity participation based on circadian needs, and the mechanisms underlying timed activities, has the potential to change how and when activities for persons with dementia are provided.