Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
BMJ Open. 2021 Nov 26;11(11):e054885. doi: 10.1136/bmjopen-2021-054885.
Bidirectional associations have been reported between sleep disturbance and both cognitive impairment, including Alzheimer's disease and amyloid beta-peptide (Aβ) accumulation. These relationships can be explained by the glymphatic system, which acts as a garbage drainage system in the brain. As interstitial fluid dynamics are suggested to increase during sleep, clearance of Aβ can be influenced by sleep disturbance or deprivation. We hypothesised that using lemborexant, an orexin receptor antagonist, to improve sleep quality would also improve the function of the glymphatic system. We plan to examine the effect of lemborexant on sleep quality and the glymphatic system among patients with insomnia disorder.
This pilot study is designed as an open-label, single-arm, single-centre trial. Thirty patients aged 50 years and over with insomnia will be recruited. The participants will take lemborexant (5 mg) at bedtime for 12 weeks and undergo a home-based sleep study at baseline and weeks 4 and 12, as well as MRI examinations to evaluate the glymphatic system at baseline and week 12. The primary outcome will be changes in objective sleep parameters as evaluated using a sleep monitoring system. The secondary outcomes will be changes in subjective sleep parameters. The relationships between changes in sleep parameters and the glymphatic system will be evaluated using diffusion tensor image analysis along the perivascular space, which is called the ALPS-index. Sleep parameters and the ALPS-index will be analysed using a paired t-test or Pearson's correlation coefficient.
The study protocol was approved by Nagoya University Certified Review Board. The findings from this research will be published in peer-reviewed journals and be presented at local, national and international conferences.
jRCTs041210024.
睡眠障碍与认知障碍（包括阿尔茨海默病和淀粉样β肽（Aβ）积累）之间存在双向关联。这些关系可以用作为大脑中垃圾清除系统的神经淋巴系统来解释。由于间质液动力学在睡眠期间被认为会增加，因此 Aβ 的清除可能会受到睡眠障碍或剥夺的影响。我们假设，使用雷美替胺（orexin 受体拮抗剂）改善睡眠质量也会改善神经淋巴系统的功能。我们计划研究雷美替胺对失眠症患者睡眠质量和神经淋巴系统的影响。
这项初步研究设计为开放标签、单臂、单中心试验。招募 30 名年龄在 50 岁及以上的失眠症患者。参与者将在睡前服用雷美替胺（5mg），持续 12 周，并在基线和第 4 周和第 12 周进行家庭睡眠研究，以及在基线和第 12 周进行 MRI 检查以评估神经淋巴系统。主要结局将是使用睡眠监测系统评估的客观睡眠参数的变化。次要结局将是主观睡眠参数的变化。将使用弥散张量成像分析沿血管周围空间（称为 ALPS 指数）评估睡眠参数变化与神经淋巴系统之间的关系。使用配对 t 检验或 Pearson 相关系数分析睡眠参数和 ALPS 指数。
该研究方案已获得名古屋大学认证审查委员会的批准。本研究的结果将发表在同行评议的期刊上，并将在本地、国家和国际会议上展示。
jRCTs041210024。
