Blue-White Light Therapy for Circadian Sleep Disorders in Alzheimer's Disease

描述（由申请人提供）：夜间睡眠紊乱在阿尔茨海默病和相关痴呆（ADRD）老年人中很常见，对受影响者的日间功能和护理人员的健康产生显著的负面影响。镇静药物是治疗睡眠障碍的常规药物，其有效性有限，并增加了这一人群的风险。ADRD中的睡眠紊乱几乎总是伴随着昼夜节律系统的明显紊乱，研究已经确定，受控的明暗光周期将使该系统与24小时太阳日同步。在患有ADRD的老年疗养院居民中进行的光疗法临床试验已经确定了统计学上显着但对睡眠的适度影响;然而，大多数人使用的治疗系统效率低下且耐受性差。 利用光生物学基础研究的最新发现和迄今为止从临床试验中吸取的经验教训，这项2期临床试验将评估一种新的、改进的方法的有效性、耐受性和安全性，这种方法将光作为治疗ADRD睡眠障碍的方法。在这种方法的创新是：a）使用新的可用，窄带（峰值？= 460 nm）光源，其将在较低水平的视觉亮度下提供更大的昼夜节律刺激; B）使用新的递送系统，其将允许将治疗应用于生活空间，而不是要求受试者坐在光板前; c）将研究限制于患有ADRD的人，其具有睡眠障碍并且不具有需要专门护理的原发性睡眠障碍;以及d）在家庭环境中的应用，并评估干预措施对家庭照顾者的影响。该试验将招募和研究18人，每个人将接受6周的干预和6周的低昼夜节律刺激红灯控制条件。主要结果将是睡眠潜伏期，持续时间和效率，通过腕关节活动记录仪测量，以及家庭护理人员报告的负担和睡眠麻烦。该研究还将确定干预对参与者的可接受性，潜在不良反应的发生率，并将使用新型昼夜节律光度计测量参与者眼睛水平的昼夜节律和视觉刺激量。该研究团队由来自领先的长期护理研究中心和全国知名照明研究中心的跨学科科学家组成。 拟议的照明方案是切实可行的，不限制行动，可以以适当的费用复制。因此，如果拟议的初步研究成功，随后的大型试验得到证实，这种治疗可以改善数百万患有痴呆症和临床显著的昼夜节律相关睡眠障碍的老年人的健康，福祉和安全性，并使他们的照顾者受益。 公共卫生相关性：美国目前约有500万人患有阿尔茨海默病及相关疾病（ADRD），预计到2050年，这一数字将增长到1200万至1400万。睡眠障碍影响到大多数人，导致进一步的功能障碍和早期机构化的风险，以及对家庭照顾者的心理健康，睡眠模式和身体健康产生负面影响。现有的治疗方法相对无效，并且与不良事件的高风险相关。因此，改善ADRD患者的睡眠问题治疗将改善患者和家庭照顾者的健康结果，并有可能降低整体医疗保健支出，并推迟这一庞大且不断增长的患者群体的养老院安置。

DESCRIPTION (provided by applicant): Disturbed night-time sleep is common in older persons with Alzheimer's disease and related dementias (ADRD), leading to significant negative effects on the daytime function of the affected person and on the well-being of caregivers. Sedating drugs, the conventional treatment for disturbed sleep, have limited effectiveness and pose increased risk in this population. Disturbed sleep in ADRD is virtually always accompanied by marked disturbances of the circadian system, and research has established that controlled bright-dark light cycles will synchronize that system to the 24-hour solar day. Clinical trials of light therapy in unselected nursing home residents with ADRD have identified statistically significant but modest effects on sleep; however, most have used treatment systems that are inefficient and poorly tolerated. Taking advantage of recent findings from basic research on photobiology and the lessons learned from clinical trials to date, this phase 2 clinical trial will evaluate the efficacy, tolerability, and safety of a novel, refined method of delivering light as therapy to persons with ADRD who have disturbed sleep. Among the innovations in this method are: a) use of newly available, narrow band (peak ? = 460 nm) light sources that will provide greater circadian stimulation at lower levels of visual brightness; b) use of a novel delivery system that will allow the treatment to be applied to living spaces instead of requiring subjects to sit in front of light panels; c) restriction of the study to persons with ADRD who have disturbed sleep and do not have a primary sleep disorder requiring specialty care; and d) application to the home setting, with assessment of the impact of the intervention on family caregivers. The trial will enroll and study 18 persons, each of whom will receive 6 weeks of the intervention and 6 weeks of a low circadian-stimulating red light control condition. Primary outcomes will be sleep latency, duration and efficiency, measured by wrist actigraphy, and burden and caregiving hassles reported by family caregivers. The study will also determine the acceptability of the intervention to participants, the prevalence of potential adverse effects, and will measure, using a novel circadian light meter, the amount of circadian and visual stimulation achieved at participant eye level. The study team consists of an interdisciplinary group of scientists from a leading long-term care research center and a nationally-prominent lighting research center. The proposed lighting scheme is practical, does not restrict movement, and could be replicated at modest cost. Therefore, if the proposed preliminary study were successful and subsequent larger trials confirmatory, such a treatment could improve the health, well-being, and safety of several million elderly who have dementia and clinically significant circadian-related sleep disorders, and also benefit their caregivers. PUBLIC HEALTH RELEVANCE: Approximately five million persons in the U.S.A. currently suffer from Alzheimer's Disease and Related Disorders (ADRD), and that number is anticipated to grow to between 12 and 14 million by 2050. Sleep disturbances affect the majority, leading to further functional impairment and a risk of early institutionalization, as well as having negative impact on the mental health, sleep patterns, and physical health of family caregivers. Existing treatments are relatively ineffective and are associated with a high risk of adverse events. Therefore, improved treatment of sleep problems in persons with ADRD would improve health outcomes of both the person with the disease and of family caregiver, and has the potential to reduce overall health care expenditures and delay nursing home placement for this large and growing patient population.