Nighttime Agitation and Restless Legs Syndrome in People with Alzheimer's Disease

阿尔茨海默病患者的夜间躁动和不宁腿综合症

• 批准号: 9512003
• 负责人: CHRISTINE R KOVACH
• 金额: $ 15.65万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-29 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9512003
• 关键词: Address; Adverse effects; Adverse event; Aggressive behavior; Agitation; Alzheimer' s Disease; Anemia; Antidepressive Agents; Antipsychotic Agents; Apnea; Appearance; Bed rest; Behavior; Behavioral; Caregiver Burden; Caregivers; Caring; Cessation of life; Circadian Rhythms; Clinical Trials; Cognition; Complex; Consensus; Control Groups; Data; Data Sources; Dementia; Diagnosis; Diagnostic Procedure; Distress; Double-Blind Method; Effectiveness; Elderly; Environment; Esthesia; Etiology; Evaluation; Fatigue; Frequencies; Future; Hour; Institutionalized Persons; Intervention; Interview; Iron; Knowledge; Leg; Light; Measures; Mediating; Medical History; Methods; Moods; Movement; Neurodegenerative Disorders; Nursing Homes; Obstructive Sleep Apnea; Outcome; Patients; Pattern; Periodicity; Persons; Pharmaceutical Preparations; Pharmacology; Pilot Projects; Placebo Control; Placebos; Polysomnography; Population; Prevalence; Provider; Quality of life; Randomized; Randomized Clinical Trials; Reporting; Research; Restless Legs Syndrome; Safety; Sensory; Sleep; Sleep Disorders; Sleep disturbances; Stroke; Symptoms; Testing; Training; Treatment Failure; United States Food and Drug Administration; Work; arm; clinical practice; cognitive skill; community setting; cost; dementia care; effective therapy; fall risk; falls; follow-up; gabapentin; improved; patient population; personalized approach; pilot trial; precision medicine; statistics; suprachiasmatic nucleus; tool; treatment group

Project Summary/Abstract. Nighttime agitation, defined as the appearance or exacerbation of behavioral disturbances, such as wandering and aggression, in the afternoon and/or evening, is a prevalent symptom in persons with Alzheimer’s disease that reduces their quality of life and restricts their environments. Effective treatments are lacking. One major cause for past failure of treatments has been the approach of treating all nighttime agitation alike. Unlike interventions in the past, our precision medicine approach tailors the intervention to a specific sleep disorder, restless legs syndrome (RLS). RLS occurs in 10-14% of older adults and it is likely that persons with Alzheimer’s disease have RLS, since it is quite common, but it is infrequently identified because diagnosis is dependent on patients answering complex questions about their symptoms. RLS causes an urge to move associated with uncomfortable and unpleasant leg sensations. The urge to move and leg discomfort only occur or worsen at night, and relief is by movement. We hypothesized that RLS might be an etiology for nighttime agitation because: 1) circadian patterns of nighttime agitation and RLS symptoms are almost identical; 2) unrelieved RLS discomfort may precipitate behaviors such as screaming and requests for help, and the urge to move may cause wandering, pacing, and restlessness; and 3) factors common in institutionalized persons with Alzheimer’s disease, such as anemia, prolonged bed rest, and antidepressants, trigger or worsen RLS. Our preliminary work supports our hypothesis, and provides beginning evidence that RLS may be an unidentified etiology for nighttime agitation. In 59 persons with dementia and nighttime agitation, and RLS diagnosed using objective measures, we found that almost ¼ had RLS and that RLS was associated with nighttime agitation (r = 0.31, p .01). We now propose a pilot clinical trial to determine if RLS treatment reduces nighttime agitation, improves sleep, reduces antipsychotic medications, and the mechanism for these effects. We have chosen gabapentin enacarbil (GEn) as the treatment because it is FDA approved for RLS and has a favorable safety profile. We propose an 8-week, double-blind placebo-controlled randomized pilot trial of GEn versus placebo in 136 nursing home residents with moderate to severe Alzheimer’s disease, nighttime agitation, and RLS, followed by an 8-week post-trial evaluation of antipsychotic medication use. The specific aims are to: 1) Determine the effect of GEn, compared to placebo on nighttime agitation (primary endpoint); 2) Describe the safety profile of GEn compared to placebo in this population; 3) Estimate the effect size of GEn compared to placebo on nighttime sleep, RLS behaviors, and antipsychotic medications; 4) Explore whether frequency of RLS behaviors mediates the effect of GEn on nighttime agitation behaviors. The results of this study and future definitive trials may shift and improve standards of care for treatment of nighttime agitation; reduce elopement, aggression, and other nighttime agitation behaviors; and improve sleep.

项目摘要/摘要。夜间躁动，定义为行为的出现或加剧 下午和/或晚上的干扰，例如徘徊和攻击性，是以下人群的普遍症状 患有阿尔茨海默病的人会降低他们的生活质量并限制他们的环境。有效的 缺乏治疗。过去治疗失败的一个主要原因是治疗所有疾病的方法 夜间躁动相似。与过去的干预措施不同，我们的精准医疗方法针对 对特定睡眠障碍——不宁腿综合征（RLS）的干预。 10-14% 的老年人出现 RLS 患有阿尔茨海默病的人很可能患有不宁腿综合征，因为这种情况很常见，但很少见 之所以能够确定，是因为诊断取决于患者回答有关其症状的复杂问题。 不宁腿综合症会引起与不舒服和不愉快的腿部感觉相关的移动冲动。想要搬家的冲动 腿部不适仅在夜间出现或加重，可通过运动缓解。我们假设 RLS 可能 成为夜间躁动的病因，因为：1) 夜间躁动和 RLS 症状的昼夜节律模式 几乎相同； 2) 未缓解的不宁腿不适可能会引发尖叫和提出要求等行为 寻求帮助，而想要移动的冲动可能会导致徘徊、踱步和不安； 3）常见因素 患有阿尔茨海默病的住院患者，如贫血、长期卧床和抗抑郁药物， 引发或恶化 RLS。我们的初步工作支持我们的假设，并提供了初步证据 RLS 可能是夜间躁动的一个未确定的病因。 59 名患有痴呆症和夜间活动的人 躁动，并且使用客观措施诊断不宁腿综合症，我们发现几乎 1/4 患有不宁腿综合症，并且不宁腿综合症是 与夜间躁动有关（r = 0.31，p = .01）。我们现在提议进行一项试点临床试验，以确定 RLS 是否 治疗可以减少夜间躁动，改善睡眠，减少抗精神病药物的使用，其机制 为了这些效果。我们选择加巴喷丁依那卡必 (GEn) 作为治疗方法，因为它已获得 FDA 批准用于治疗 RLS 具有良好的安全性。我们建议进行为期 8 周的双盲安慰剂对照随机试验 在 136 名患有中度至重度阿尔茨海默病的疗养院居民中进行了 GEn 与安慰剂的试点试验， 夜间躁动和 RLS，然后进行为期 8 周的抗精神病药物使用试验后评估。这 具体目标是： 1) 确定 GEn 与安慰剂相比对夜间躁动的影响（主要 终点）； 2) 描述该人群中 GEn 与安慰剂相比的安全性； 3）估计效果 与安慰剂相比，在夜间睡眠、RLS 行为和抗精神病药物方面的 GEn 大小； 4）探索 RLS 行为的频率是否介导 GEn 对夜间躁动行为的影响。结果 这项研究的结果和未来的最终试验可能会改变并提高夜间治疗的护理标准 搅动;减少私奔、攻击和其他夜间躁动行为；并改善睡眠。