Effect of Light and Melatonin on Circadian Physiology in the Elderly.

Age-related alterations in each component of the circadian system are well documented but the way these alterations translate into the observed changes in circadian rhythmicity and whether they contribute to the sleep problems reported by elderly are still not known. Therefore, one of the aims of this thesis was to examine the differences in spectral sensitivity between young and elderly people. In addition, studying the differences in spectral sensitivity between elderly with and elderly without sleep problems aimed to investigate whether these changes contribute to reported sleep problems. Adapting and evaluating the protocol used in this study aimed to investigate differences in spectral sensitivity between patients suffering from type 1 diabetes mellitus. Further aims of this thesis were to investigate age-related changes in the amplitude and timing of the melatonin rhythm and the relationship of these parameters to sleep in the elderly. In addition the phase relationship between melatonin and sleep in the elderly was assessed in order to study their contribution to the sleep disturbances reported. A final aim was to investigate the effectiveness of exogenous melatonin administration compared with placebo on sleep in elderly women with self-reported sleep problems. Following exposure to short wavelength light (lambdamax 456: 3.8 and 9.8 muW/cm2 for 30 mins), a significantly reduced melatonin response was noted in elderly compared to young women. By contrast no age-dependent difference in the degree of melatonin suppression was seen following exposure to medium wavelength light (lambdamax 548 nm: 28 and 62 muW/cm2). The response to short and medium wavelength light did not differ between elderly women with and without sleep problems. The protocol used in this study was adapted and evaluated for use with young type 1 diabetic patients in order to investigate the effectiveness of short wavelength light to suppress nocturnal melatonin in these subjects. Significantly reduced urinary 6-sulphatoxymelatonin (aMT6s) production (mug/24 h) and an advance in the timing of the urinary aMT6s rhythm and plasma dim light melatonin onset (DLMO) were noted in elderly compared to young women. However, no difference was seen in these parameters between elderly women with and those without self-reported sleep problems. Overall, no relationship was found between the melatonin parameters and subjectively and objectively assessed sleep. However, some differences in the timing of the melatonin rhythm compared to the sleep rhythms were observed. The time interval between DLMO and sleep onset was significantly longer in the elderly women with sleep problems. The time interval between the peak of the aMT6s rhythm and sleep offset was reduced (but not significantly, p=0.08) in women with sleep problems. Finally, exogenous melatonin (5 mg) taken 30 mins before bedtime for 4 weeks failed to improve subjectively and actigraphically assessed sleep, compared to placebo in 11 postmenopausal women with self-reported sleep problems. For the first time an age-related reduction in sensitivity to short wavelength light has been demonstrated, probably due to age-related changes in lens density. However, the findings suggest that it is unlikely that this reduced response contributes in a major way to the sleep problems of otherwise healthy and mobile elderly women. Neither the amplitude nor the timing alterations observed in the melatonin rhythm in the elderly seem to associate with the reported sleep disturbances. However, alterations in the phase relationship between melatonin and sleep timing may underlie some of the sleep problems. Better understanding of the cause of the sleep problem may aid in finding a therapeutic agent that improves sleep quality in the elderly, since melatonin administration failed to improve sleep in most of the studied subjects