Melatonin Reorganizes the Sleep EEG Spectral Power in Alzheimer's Disease: a Preliminary Principal Component Analysis-Based Comparison of Placebo and Treatment Effects.

OBJECTIVES:Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, tau pathology, and cortical atrophy, leading to widespread synaptic dysfunction and cognitive decline. Sleep disturbances are highly prevalent in AD and are thought to both reflect and exacerbate underlying neurodegenerative processes. Melatonin, an indoleamine synthesized by the pineal gland, is central to the regulation of circadian rhythms and sleep - wake cycles. In healthy individuals, melatonin enhances non-rapid eye movement (NREM) sleep and attenuates beta activity during wakefulness. In AD populations, it has been associated with improved sleep quality and potential neuroprotective effects against amyloid-related pathology. Electroencephalography (EEG) offers a non-invasive method to monitor neurophysiological changes associated with AD. Principal component analysis (PCA), a dimensionality reduction technique, enables the identification of latent neural patterns within complex EEG data. METHODS:In this preliminary study, PCA was applied to EEG recordings from eight individuals with mild-to-moderate AD during both wakefulness and sleep under placebo and melatonin conditions. EEG derivations included bipolar (F7-T3, F8-T4, F3-F4, O1-O2) and referential (C3-A1, C4-A2) configurations. RESULTS:Preliminary PCA suggests that melatonin administration may induce a stage-dependent reorganization of EEG spectral activity, characterized by a relative enhancement of slow-frequency activity and an apparent increase in spectral segregation during NREM sleep. DISCUSSION:These preliminary findings suggest that melatonin could optimize stage-specific neural dynamics, supporting its therapeutic potential in AD-related sleep disruption.