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Melatonin Efficacy to Treat Circadian Alterations of Sleep in Alzheimer’s Disease

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Sleep and Sleep Disorders

Summary

Alzheimer’s disease (AD) patients show a greater disruption of the circadian sleep-wake cycle as compared to similarly aged non-demented controls. When this occurs demented patients spend their nights in a state of frequent restlessness and their days in a state of frequent sleepiness. These sleep-wake disturbances became increasingly more marked with the progression of the disease and may contribute to cognitive decay. Sleep architecture in AD is characterized by decreases of slow wave sleep and rapid eye movement sleep and increases of time and frequency of awakening compared to aged-matched control subjects. The sleep-wake disturbances in elderly people and AD patients appear to result from changes at different levels: reduction of environmental synchronizers, neurosensorial deficit or lack of mental and physical activity. However, increasing evidence exists about the loss of functionality of the hypothalamic suprachiasmatic nuclei (SCN), the principal oscillator in the circadian system. A chronobiological approach including melatonin, bright-light therapy, restricted time in bed and programmed diurnal activity is a promising therapeutic alternative in the management of sleep-wake disorders in AD patients. In elderly insomniacs melatonin treatment decreased sleep latency and increased sleep efficiency. The effect of melatonin on sleep is probably the consequence of increasing sleep propensity (by inducing a fall in body temperature) and of a synchronizing effect on the circadian clock (chronobiotic effect); typically the latter takes several weeks to occur. Generally, melatonin decreased sundowning in AD patients and reduced variability of sleep onset time, with improvement in mood and memory. The effect of melatonin was seen regardless of the concomitant medication employed to treat cognitive or behavioral signs of disease. The mechanisms accounting for the possible therapeutic effect of melatonin in AD patients remain unknown. Melatonin treatment could be beneficial in AD by augmenting the restorative phase of sleep. In addition, in vitro and in vivo data indicated that melatonin protects neurons against β amyloid toxicity, prevents β amyloid-induced lipid peroxidation and alters the metabolism of the β amyloid precursor protein. Melatonin prevented the chronobiological consequences of injecting β amyloid peptide 25–35 in the SCN of hamsters and cognitive decay in transgenic mice overexpressing β-amyloid.

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Authors and Affiliations

  1. Departamento de Fisiología Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Daniel P. Cardinali, Analía M. Furio, Luis I. Brusco & Cynthia Liberczuk

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  1. Daniel P. Cardinali
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  2. Analía M. Furio
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Cardinali, D.P., Furio, A.M., Brusco, L.I., Liberczuk, C. (2006). Melatonin Efficacy to Treat Circadian Alterations of Sleep in Alzheimer’s Disease. In: Sleep and Sleep Disorders. Springer, Boston, MA. https://doi.org/10.1007/0-387-27682-3_11

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