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

 描述（由申请人提供）：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的神经退行性疾病，影响近1500万家庭护理人员（CG）。姑息模式的护理主张“上游”的人与痴呆症，以提高生活质量（QOL），减少症状负担。昼夜节律紊乱（CRD）发生在大多数患有痴呆的人中，并且包括下午晚些时候/晚上激动和不规则的睡眠-觉醒节律，例如白天嗜睡、频繁的夜间觉醒和睡眠效率差。CRD症状对CG造成了巨大的负担，并且是痛苦、生活质量差和机构化的主要原因。通过使用光和活动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，并表明在战略时间提供的认知，身体和基于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措施作为缓解方法的重要性，以减少CRD症状的频率和强度，增强人格和尊严，并提高生活质量。到目前为止，还没有试验将活动的性质和时间与关键的姑息治疗和生物行为结果联系起来。我们提出了一个明确的III期疗效试验的“健康模式”的干预，以家庭为基础的活动干预，旨在改善CRD和生活质量，建立在我们的试点工作。我们将采用随机两组平行设计，将200名痴呆患者及其CG（二人组）分配到“健康模式”干预组或同等家庭关注和社会接触的对照干预组。干预的具体组成部分包括：1）评估健康/功能状态和偏好/兴趣; 2）教育CG环境线索，以促进活动和睡眠;和3）训练CG根据昼夜节律的需要使用定时的上午，下午和晚上活动。干预的成功将取决于其对姑息结局的影响，包括QOL指标以及CRD症状的活动记录和代理报告指标。感兴趣的CG结果将是负担、主观睡眠质量和QOL。我们还将通过唾液皮质醇和弱光褪黑激素测量的昼夜神经内分泌活动来检查干预对CRD症状的作用机制。拟议研究的结果将提供有关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，以及定时活动的机制，有可能改变痴呆症患者的活动方式和时间。

 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.