Both blindness and aging are frequently associated with sleep disturbances for which medicines with undesired and potentially dangerous side effects are often prescribed. In blind individuals, these sleep disturbances may be due to misalignment of the endogenous circadian pacemaker and its outputs with respect to the sleep-wake schedule, for they lack the periodic light input necessary for entrainment of the circadian clock to the 24 hour day. Without such light input, circadian rhythms of blind individuals may """"""""free-run"""""""" at a period of the endogenous circadian pacemaker which is near-to but different from 24.00 hours. In these free- running blind people, there may be a chronic sleep and circadian rhythm disturbance whose severity varies with the relative relationship between the sleep/wake cycle and the internal clock. With aging, there is an increase in blindness and therefore the prevalence of this disability. In this research proposal, I plan to study blind older people to verify the presence of free-running circadian rhythms and then treat them with melatonin, an endogenous hormone, both to alleviate the chronic sleep problems that occur when they maintain a 24-hour schedule and to improve cognitive performance during the following waking hours. Specifically, I plan to test the hypotheses that (1) the majority of older blind patients without conscious light perception are unable to synchronize their circadian pacemakers to the 24-hour day; (2) light input to the hypothalamus and pineal is functionally absent in these blind people; (3) non-visual cognitive and psychometric performance decrements, as well as sleep, endocrine and metabolic abnormalities are found in these blind people; and (4) pre-sleep administration of physiological doses of melatonin will improve sleep, cognitive and psychomotor performance measures. Each older blind subject will be studied several times, first to establish the presence of free-running circadian rhythms and associated disorders, then during treatment with melatonin to verify improvement of sleep variables, such as sleep latency and sleep efficiency, and cognitive and performance measures. The results will be applicable to the blind community, to the older population with and without vision or light exposure problems, as well as to younger individuals on non-24 hour schedules, such as people on rotating shift work or night work schedules. Improving the sleep and performance measures of this large segment of the population using physiologic amounts of a natural hormone rather than pharmacological doses of medicines with potentially dangerous side effects has the potential to rehabilitate and improve the lives of the many individuals and their families.
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