Menczel Schrire Zoe, Phillips Craig L, Duffy Shantel L, Marshall Nathaniel S, Mowszowski Loren, La Monica Haley M, Stranks Lachlan, Gordon Christopher J, Chapman Julia L, Saini Bandana, Naismith Sharon L, Grunstein Ronald R, Hoyos Camilla M
Healthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia.
CIRUS, Centre for Sleep and Chronobiology, The Woolcock Institute of Medical Research, Macquarie University, Sydney, New South Wales, Australia.
J Pineal Res. 2024 Nov;76(8):e70019. doi: 10.1111/jpi.70019.
Melatonin has multiple proposed therapeutic benefits including antioxidant properties, circadian rhythm synchronisation and sleep promotion. Since these areas are also recognised risk factors for dementia, melatonin has been hypothesised to slow cognitive decline in older adults. Participants with Mild Cognitive Impairment (MCI) were recruited from the community for a 12-week randomised placebo-controlled parallel, feasibility trial of 25 mg oral melatonin nightly. Primary outcomes were feasibility, acceptability, and tolerability. Secondary efficacy outcomes were brain oxidative stress, cognition, mood, and sleep at 12 weeks. Forty participants (mean [SD] age = 68.2 [4.7] years; 19 female) were randomised. Feasibility, defined as those who met eligibility criteria, was 42/389, 11%. Acceptability, determined by the proportion of eligible people who agreed to be randomised, was 40/44, 91%. Tolerability, determined by adherence to the nightly melatonin and completion of the main secondary outcome (Magnetic Resonance Spectroscopy scan) was over the pre-defined 80% threshold for all participants. The study was not powered to detect effectiveness. Accordingly, there were no significant differences between melatonin and placebo interventions in any of the secondary outcomes. The protocol was developed, and successfully implemented, with the planned number of eligible participants recruited. All participants were able to complete all aspects of the trial, including online visits and assessments, with no differences in adverse events between groups. This is promising for future trials, which should conduct the study with a larger sample size and longer duration to yield necessary efficacy data.
褪黑素具有多种潜在治疗益处，包括抗氧化特性、昼夜节律同步和促进睡眠。由于这些方面也是公认的痴呆症风险因素，因此有人提出褪黑素可能减缓老年人的认知衰退。从社区招募了轻度认知障碍（MCI）参与者，进行一项为期12周的随机、安慰剂对照平行可行性试验，每晚口服25毫克褪黑素。主要结果是可行性、可接受性和耐受性。次要疗效结果是12周时的脑氧化应激、认知、情绪和睡眠。40名参与者（平均[标准差]年龄 = 68.2[4.7]岁；19名女性）被随机分组。可行性定义为符合入选标准的人，为42/389，即11%。可接受性由同意被随机分组的符合条件者的比例确定，为40/44，即91%。耐受性由对每晚褪黑素的依从性和主要次要结果（磁共振波谱扫描）的完成情况确定，所有参与者均超过了预先定义的80%阈值。该研究没有足够的效力来检测有效性。因此，在任何次要结果中，褪黑素和安慰剂干预之间均无显著差异。该方案已制定并成功实施，招募了计划数量的符合条件的参与者。所有参与者都能够完成试验的所有方面，包括在线访问和评估，两组之间的不良事件没有差异。这对未来的试验很有希望，未来试验应以更大的样本量和更长的持续时间进行，以产生必要的疗效数据。
