More than half of individuals over 65 report at least some disturbance of their sleep, especially the inability to sustain consolidate sleep throughout the night. Evidence gathered during the initial period of this project suggests strongly that age-related sleep maintenance insomnia may be mediated by a misalignment between habitual sleep times and the phase of the circadian timing system. Additionally, our preliminary results of an NIA-funded double-blind, randomized, placebo- controlled clinical trial indicated that a group of young subjects on a forced desynchrony protocol who were administered a physiologic dose of melatonin (0.3 mg) had significantly greater sleep efficiency than a comparable group administered placebo. We propose to compare results in healthy people with those from the adults in order to quantify age- related changes in the impact of circadian phase on sleep, to quantify age-related changes in the ability to tolerate small degrees of misalignment between sleep and circadian phase, and to quantify the hypnotic efficacy of a physiologic (0.3 mg) and a pharmacologic (5.0 mg) dose of melatonin in older subjects. The proposed investigation is designed to test the following hypotheses: 1) that sleep efficiency, waking alertness and neurobehavioral performance will vary markedly with circadian phase when older subjects are scheduled on a 20-hour forced desynchrony protocol, and that the sleep efficiency of healthy older people will be significantly worse at all circadian phases as compared with that of healthy young adults; 2) that the rising phase of the wake propensity rhythm will be internally phase-advanced with respect to the endogenous circadian temperature and melatonin rhythms in older subjects; 3) that pre-sleep administration of melatonin (0.3 mg ir 5.0 mg) during the forced desynchrony protocol will result in improved sleep efficiency as compared to pre-sleep administration of placebo. We propose to test these hypotheses in health and older males and female whose sleep-wake cycle is scheduled to a 20-hour day (i.e., 13.33 h wake followed by 6.67 h sleep opportunity) on a forced desynchrony protocol. Oral melatonin (0.3 mg or 5.0 mg) or placebo will be administered 30 minutes before lights out. Polysomnographic sleep recording and quantitative analyses of EEG will be used to describe age-related changes in circadian sleep regulation and understand the effects of melatonin on sleep in older persons. The results of this project should further our understanding of age- related sleep disturbance and its potential dependence on circadian misalignment. Furthermore, this project will test the efficacy of two doses of melatonin as a potential therapeutic treatment of insomnia in older people.
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