Melatonin as a potential biomarker for subclinical epileptiform activity in Alzheimer's disease: An exploratory study

Background Melatonin levels are altered in elderly people and might become even more disrupted in Alzheimer's disease (AD) patients. An inverse correlation between cerebrospinal fluid melatonin levels and severity of AD neuropathology has been described. There is an increased prevalence of subclinical epileptiform activity (SEA) in AD. Baseline melatonin levels have been described to be lower in epilepsy patients as compared to controls, suggesting antiepileptic effects. Objective To compare melatonin levels between AD participants and controls, to evaluate melatonin's potential use as biomarker for disease stage in AD and to evaluate the link between melatonin levels and SEA in AD. Methods AD subjects ( n = 20) and healthy volunteers ( n = 8) underwent a 24-h-electro-encephalography (EEG), during which multiple blood and saliva samples were taken. Melatonin levels were analysed using liquid chromatography-mass spectrometry (plasma) and radioimmunoassay (saliva). A subset of participants underwent 50-min resting magnetoencephalography and/or high-density-EEG to detect SEA. Results Plasma melatonin levels were significantly lower in AD as compared to controls at 23:00PM. Melatonin levels were similar between patients with AD dementia, MCI due to AD and preclinical AD subjects. Plasma and saliva melatonin levels at 04:00AM and 01:00AM, respectively, were significantly higher in AD participants with SEA as compared to those without. Conclusions Night-time melatonin levels might serve as a potential biomarker to identify AD patients at risk for SEA, based on exploratory findings. Whether this increase could be a compensatory feedback mechanism against SEA or whether melatonin rather has pro-epileptic effects, remains to be elucidated by further research.