Trough melatonin levels differ between early and late phases of Alzheimer disease
Chieh-Hsin Lin , Chih-Chiang Chiu , Hsien-Yuan Lane *
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan, Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan
Received: April 28, 2020; Revised: July 22, 2020; Accepted: July 30, 2020; Published online: July 30, 2020.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Aim: 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.
Method: 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.
Results: 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.
Conclusion: 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.
Keywords: melatonin, Alzheimer’s disease, mild cognitive impairment, cognitive function, CDR, MMSE