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

描述(申请人提供)：阿尔茨海默病和相关痴呆症(ADRD)的老年人夜间睡眠障碍很常见，对患者的白天功能和照顾者的福祉造成严重的负面影响。镇静药物是治疗睡眠障碍的常规疗法，但在这一人群中效果有限，风险增加。ADRD受扰的睡眠几乎总是伴随着昼夜节律系统的显著干扰，研究已经证实，受控的明暗光周期将使该系统与24小时太阳日同步。在未选定的患有ADRD的疗养院居民中进行的光疗临床试验发现，对睡眠的影响在统计上是显著的，但影响不大；然而，大多数人使用的治疗系统效率低下，耐受性差。 利用光生物学基础研究的最新发现和迄今从临床试验中吸取的教训，这项第二阶段临床试验将评估一种新颖、精致的方法的有效性、耐受性和安全性，该方法将向扰乱睡眠的ADRD患者提供光作为治疗。这种方法的创新之处包括：a)使用新获得的窄带(峰值=460 nm)光源，该光源将在较低的视觉亮度水平下提供更大的昼夜节律刺激；b)使用新型传递系统，允许将治疗应用于居住空间，而不是要求受试者坐在光板前；c)将研究限制在扰乱睡眠且没有原发睡眠障碍需要特殊护理的ADRD患者；以及d)应用于家庭环境，评估干预措施对家庭照顾者的影响。这项试验将招募和研究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，通过腕部活动描记来衡量，以及家庭照顾者报告的负担和照顾麻烦。这项研究还将确定参与者对干预措施的接受程度、潜在不良影响的流行率，并将使用一种新型的昼夜节律测光仪来测量参与者眼睛水平实现的昼夜节律和视觉刺激量。研究团队由来自一家领先的长期护理研究中心和一家全国知名的照明研究中心的跨学科科学家组成。 建议的照明方案是实用的，不限制移动，并且可以以适中的成本复制。因此，如果拟议的初步研究成功，并且随后的更大规模试验得到证实，这样的治疗可以改善数百万患有痴呆症和临床上明显的昼夜节律相关睡眠障碍的老年人的健康、幸福感和安全性，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。睡眠障碍影响大多数人，导致进一步的功能损害和早期住院的风险，并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，并与不良事件的高风险相关。因此，改善ADRD患者睡眠问题的治疗将改善患者和家庭照顾者的健康状况，并有可能减少总体医疗保健支出，并推迟这一庞大且不断增长的患者群体的疗养院安置。

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.