Plasma melatonin night‐time peak levels and 24‐hour area under the curve profile seem higher in AD patients with epileptiform activity than in those without

Abstract

AbstractBackgroundPlasma melatonin levels drop in elderly, which might become more pronounced in Alzheimer’s disease (AD) as compared to controls.(1) Melatonin can serve as a potential biomarker for AD, given the inverse correlation between cerebrospinal fluid (CSF) melatonin levels and severity of neuropathology (Braak stages).(2) Due to suggested antiepileptic effects(6), melatonin can potentially slow down disease progression as epileptiform activity may contribute to AD disease progression.(3‐5). We here present a preliminary interim analysis of an ongoing study.Aims1. To evaluate melatonin’s potential as biomarker for AD by comparing blood melatonin levels between patients with mild cognitive impairment (MCI) and dementia due to AD and preclinical AD subjects.2. To study the link between melatonin levels and epileptiform activity in AD.MethodsAll subjects underwent a neuropsychological examination, and lumbar puncture for analysis of core AD CSF biomarkers or amyloid brain PET. Subjects belonging to the AD continuum (dementia [n = 7]; MCI [n = 4]; preclinical AD [n = 1]) were diagnosed according to the NIA‐AA research criteria. A subset of subjects (n = 6) underwent 50‐minute magnetoencephalography to detect epileptiform activity. Blood samples were taken multiple times during a 24‐hour period, in in‐hospital controlled circumstances, and were analysed by use of liquid chromatography‐mass spectrometry.ResultsAD patients with epileptiform activity (n = 2) tended to have a higher melatonin 24‐hour area under the curve (AUC) and peak concentration (AUC 517.9pg/ml.h [+/‐140.1pg/ml.h] versus 204.5pg/ml.h [+/‐115.5pg/ml.h]; peak 65.4pg/ml [+/‐14.6pg/ml] versus 25.8pg/ml [+/‐17.5pg/ml]) than AD patients without (n = 4) (p = 0.064 for both; MWU test). There was no statistical difference regarding the melatonin 24‐hour plasma AUC or peak levels between patients with dementia, MCI, preclinical AD subjects (p = 0.760 for both; Kruskall‐Wallis test). We have to interpret these data with caution since sample sizes are still small and more patients are being recruited.ConclusionOn the basis of very preliminary data, 24‐hour plasma melatonin profile and peak plasma melatonin concentration tended to be higher in AD patients with epileptiform activity than in those without. Whether this could be a potential compensatory mechanism against epileptiform activity in AD or whether melatonin could rather have pro‐epileptic effects, remains to be elucidated in future research.