Melatonin rhythmicity: effect of age and Alzheimer's disease

The circadian rhythm of the pineal gland hormone, melatonin is generated within the hypothalamic suprachiasmatic nuclei (SCN), site of the circadian clock. The circadian clock and its output melatonin rhythm is synchronized to the 24h day by environmental light which is transmitted from the retina to the SCN primarily via the retinohypothalamic tract. Changes in both the amplitude and timing of the melatonin rhythm have been reported with aging in humans. Whether these age-related changes (reduced melatonin amplitude, earlier timing of melatonin rhythm) are a result of aging of the retina, the SCN clock, the pineal gland, their neural connections or a combination of some or all of these is not known. The fragmented sleep/wake patterns observed in the elderly and to a greater extent in patients with Alzheimer's disease have been shown to be partly related to an altered retina-SCN-pineal axis. Therapies designed to reinforce the circadian axis (for example, administration of melatonin or light) have been reported to alleviate the disturbed circadian rhythms and disrupted sleep. Future research needs to pinpoint the site(s) of age-related dysfunction so that therapies can be specifically tailored to correct the abnormality in addition to reinforcing any of the intact processe

Use of melatonin in the treatment of phase shift and sleep disorders

When administered to humans the pineal hormone melatonin can phase shift a number of circadian rhythms. This property has prompted the investigation of exogenous melatonin in sleep disorders known to have an underlying chronophysiological basis (i.e. circadian rhythm sleep disorders). Both in field and simulated studies of jet lag and shift work suitably timed melatonin improved sleep and, in some cases, hastened readaptation of the circadian rhythms following the phase shift. Melatonin treatment has also been evaluated in the circadian sleep disorders: delayed sleep phase syndrome (DSPS) and non-24-hour sleep wake disorder. Compared with placebo, melatonin advanced the sleep period in subjects with DSPS. Melatonin also improved a number of sleep parameters in blind subjects suffering from non-24-hour sleep wake disorder

Visual impairment and circadian rhythm sleep disorders

Many aspects of human physiology, metabolism, and behavior are dominated by 24-h circadian rhythms including the sleep-wake cycle, alertness and performance patterns, and some hormones. These rhythms are spontaneously generated by an internal circadian clock in the brain and daily light exposure to the eyes synchronizes the clock with the external environment. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the circadian pacemaker, resulting in non-24-h sleep-wake disorder. Daily melatonin administration, which provides a replacement synchronizing daily �time cue,� is a promising therapeutic strategy to treat this disorder. © 2017 Elsevier Inc. All rights reserved