Melatonin Effects on EEG Activity During Sleep Onset in Mild-to-Moderate Alzheimer’s Disease: A Pilot Study

Abstract

There is evidence demonstrating that 5-mg of fast-release melatonin significantly reduces nocturnal sleep onset in patients with mild-to-moderate Alzheimer’s disease (AD). However, the physiological mechanism that could promote sleep installation by melatonin in patients with AD is still poorly understood. The present pilot study was designed to analyze the effects of melatonin on cortical activity during the sleep onset period (SOP) in eight mild-to-moderate AD patients treated with 5-mg of fast-release melatonin. Electroencephalographic recordings were obtained from C3-A1, C4-A2, F7-T3, F8-T4, F3-F4, and O1-O2. The relative power (RP), interhemispheric, intrahemispheric, and fronto-posterior correlations of six electroencephalographic bands were calculated and compared between two conditions: placebo and melatonin. Results show that at F7-T3, F3-F4, and C3-A1, melatonin induced an increase of the RP of the delta band. Likewise, in F7-T3, melatonin induced a decrease of the RP in the alpha1 band. Similarly, results show a lower interhemispheric correlation between the F7-T3 and F8-T4 derivations in the alpha1 band compared to the placebo condition. We conclude that the short sleep onset related to melatonin intake in AD patients was associated with a lower RP of the alpha1, a higher RP of the delta band (mainly in the left hemisphere) and a decreased interhemispheric EEG coupling in the alpha1 band. The possible role of the GABAergic neurotransmission as well as of the cascade of neurochemical events that melatonin triggers on sleep onset are discussed.

Pharmacological and non‐pharmacological interventions to enhance sleep in mild cognitive impairment and mild Alzheimer's disease: A systematic review

“…A reduction in sleep latency was also demonstrated in a small pilot study of 8 participants by Cruz‐Aguilar et al. ( 2018 ) utilising polysomnography. This single‐blind placebo‐controlled crossover study was conducted over three nights with a habituation night followed by placebo or melatonin, subsequently reversed for the final night.…”

“…( 2020 ) in a further analysis of data from the same study described in Cruz‐Aguilar et al. ( 2018 ). Following melatonin administration, mean sleep latencies to all stages of NREM decreased significantly, NREMS‐1: Placebo = 36.63 min SE [7.37], Melatonin = 12.18 min [SE 1.07], t = 3.66, p = .008), NREMS‐2: Placebo = 44.62 min [SE 8.03], Melatonin = 21.06 [SE 1.82], t = 2.86, p = .02, NREMS‐3: Placebo = 176.12 min [SE 6.28], Melatonin = 84.31 [SE 4.54], t = 13.40, p = <0.001.…”

“…The overall quality of included studies as measured by the appropriate Joanna Briggs Quality Appraisal Tool was variable. Multiple limitations were identified in one study (Cruz‐Aguilar et al., 2018 ), however this was partly due to inherent difficulties in concealment and blinding associated with utilising a psychotherapeutic intervention. One further study had 3 limitations identified (Cooke et al., 2006 ), three studies had two limitations identified (Naismith et al., 2018 ; Petit et al., 1993 ; Wang et al., 2020 ).…”

“…Melatonin appeared to significantly reduce sleep latency both when analysed utilising PSG by Cruz‐Aguilar et al. ( 2018 ) and utilising actigraphy by Jean‐Louis et al. ( 1998 ) who also demonstrated a reduction in overnight transitions from sleep to wakefulness.…”

Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives

“…Furthermore, it ameliorates Aβ-induced neurotoxicity by promoting Aβ clearance via glymphatic-lymphatic drainage, transport across the BBB, and degradation pathways [147][148][149]. In this regard, several clinical trials have studied the effect of exogenous melatonin administration in AD patients, with most of them showing an improvement in sleep quality and cognitive function [150][151][152][153]. Therefore, increased availability of melatonin could constitute a new therapeutic target [154].…”