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Circulating melatonin is metabolized primarily in the liver, and secondarily in the kidney. Melatonin has been used successfully in the treatment of insomnia and circadian rhythm sleep disorders. Several studies show that melatonin levels are lower in Alzheimer's disease (AD) patients compared to age-matched control subjects. If the expectation of melatonin activity in AD is to be neuroprotective, the treatment must be initiated at the earliest possible stage of the disease. There is substantial evidence that fragmented sleep, advanced sleep phase syndrome, insomnia, and impaired daytime alertness seen in advanced age are the result of brain dysfunction that is closely linked to disruptions in the regulation of circadian rhythms. The aging process is multifactorial, and no single factor seems to be of basic importance. An example of the effect melatonin has on aging is that in AD and mild cognitive impairment (MCI) patients.
Symptoms of abnormally early sleep are common in the elderly. Aging is associated with earlier habitual bedtimes and earlier morning wake-up times. Intrinsic disorders, are those in which the endogenous circadian regulation of sleep is itself abnormal. These intrinsic disorders include irregular sleep-wake rhythm, free-running disorder, and delayed sleep phase syndrome (DSPS), as well as advanced sleep phase syndrome (ASPS). Amplitudes of other circadian rhythms, including core body temperature, are also reduced with age, and post-mortem brain studies have revealed reductions in suprachiasmatic nucleus (SCN) volume, cell number, and neuropeptide rhythms, suggesting an age-related clock defect. Treatments recommended for ASPS include chronotherapy, timed melatonin administration, and timed light exposure. These treatments are all directed towards the primary goal in treating ASPS: to correct the abnormally early timing of sleep by delaying the circadian clock.
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