Lin Chieh-Hsin, Chiu Chih-Chiang, Lane Hsien-Yuan
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taipei, Taiwan.
Clin Psychopharmacol Neurosci. 2021 Feb 28;19(1):135-144. doi: 10.9758/cpn.2021.19.1.135.
Melatonin has been considered to have an essential role in the pathophysiology of Alzheimer's disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn't show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits.
We enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment.
In the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort.
This study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies.
褪黑素因其对昼夜节律的调节功能以及与谷氨酸相互作用对学习和记忆的调节作用，被认为在阿尔茨海默病（AD）的病理生理学中起重要作用。先前的研究表明，AD患者的褪黑素水平降低。然而，补充褪黑素对AD并未显示出有前景的疗效。本研究比较了不同认知缺陷严重程度的老年人的褪黑素谷值水平。
我们在学习队列中纳入了270名老年人（分为四组：健康老年人、遗忘型轻度认知障碍[MCI]、轻度AD和中度至重度AD）。采用酶联免疫吸附测定法（ELISA）测量血浆中的褪黑素谷值水平。通过临床痴呆评定量表（CDR）和简易精神状态检查表（MMSE）评估认知功能。还纳入了一个同样由四组组成的独立测试队列进行验证。
在学习队列中，MCI组的褪黑素谷值水平降低，而轻度和中度至重度AD组的褪黑素谷值水平升高。MCI或AD患者的褪黑素谷值水平与CDR和MMSE显著相关。在测试队列中，结果与学习队列相似。
本研究表明，外周血中的褪黑素谷值水平在MCI中降低，但随着AD严重程度的增加而升高。这一发现支持了相关试验，即褪黑素仅在MCI中显示出疗效，而在AD中则不然。褪黑素谷值水平是否有可能成为AD尤其是其早期阶段的治疗反应生物标志物，还需要进一步研究。
