Circadian and sleep disturbances in the elderly
Introduction
The present paper reviews changes in the circadian organization of sleep at old age. Circadian rhythms are rhythms of about 24-h that occur in most physiological processes and overt behavior. Even isolated from cues related to 24-h cyclic patterns in the environment (like light and darkness), most of these rhythms persist with a period of approximately, but not exactly 24-h. Under normal exposure to 24-h cyclic patterns in the environment, the rhythms normally synchronize or ‘entrian’ exactly to this 24-h cycle. Circadian rhythms have been attributed adaptive values, which usually go unnoticed, but can surface painfully clear when derangements occur. The hypothalamic suprachiasmatic nucleus has been recognized as the central clock of the brain, capable of generating near-24-h cycles in cell firing patterns, of synchronizing these cycles to environmental clues, and of cyclic control of brain structures involved in e.g. regulation of arousal, body temperature and hormones. With aging many aspects of the circadian regulation show changes. A reduced amplitude is no doubt the most prominent age-related change in circadian functioning, found in the regulation of arousal, body temperature, hormones and other variables. Changes have also been demonstrated in several other aspects of the circadian timing system, e.g. its period, amplitude, synchronization with the environment, resynchronization speed, range of entrainment, regularity, sensitivity to environmental clues of ‘Zeitgeber’, internal coupling of several rhythms (phase-relationships) and the consequences of misalignment of the phase relationships (reviewed in Dijk et al., 2000, Weinert, 2000). An age-related reduction in the circadian amplitude can already be demonstrated at the base, in the human aging clock itself (reviewed in Hofman, 2000). The aging suprachiasmatic nucleus (SCN) is characterized by decreased neuronal activity (Swaab et al., 1985, Swaab et al., 1992). Both the amount and the synthesis of vasopressin, one of the main peptides in the SCN, which shows a circadian rhythm in humans, is compromised in elderly subjects. An even lower vasopressin expression has been demonstrated in the SCN of Alzheimer patients and may underlie the extremely disturbed sleep–wake rhythms that these patients often show. Alterations in the regulation of circadian rhythms are furthermore thought to contribute to the symptoms of a number of other conditions for which the risk is increased in old age, e.g. sleep disturbances and depression. The present paper focuses on the possible mechanisms by which a deranged circadian timing system may be involved in sleep disturbances. A large amount of studies has addressed this relation in the last decade, because of the high frequency and strong impact of sleep disturbances in the elderly. First, a brief resumé of the epidemiology and impact of age-related sleep disturbances is presented. Second, the likeliness of involvement of the circadian timing system in age-related sleep disturbances is described. Third, a brief overview of chronobiological treatment methods and their effectivity is given.
Section snippets
Epidemiology and consequences of age-related changes in circadian sleep–wake rhythm regulation
Epidemiological studies indicate that 40–70% of the elderly population suffers from chronic sleep disturbances (Buysse et al., 1991, Campbell et al., 1993, Cutler et al., 1997, Fry, 1987, Maggi et al., 1998, Middelkoop et al., 1994, Uchimura et al., 1998), and only about 20% do not report any sleep disturbance at all (Espinosa-Fernandes et al., 1998, Foley et al., 1995, Maggi et al., 1998). Long-term prospective studies indicate that the sleep disturbances increase with age in a cohort of
The involvement of the circadian timing system in age-related sleep disturbances
Although factors like sleep apnea, restless legs, chronic disease and medication all contribute to the increased frequency of sleep disturbances in the elderly, changes in the circadian timing system, with the SCN as its core, may play a pivotal role when other factors can be excluded. As has been mentioned in the introduction, a decreased amplitude and stability of the circadian pacemaker at high age is reflected at all stages ranging from the SCN itself to overt behavior. These changes might
Chronobiological treatment of age-related sleep disturbances
Improvement of the sleep–wake rhythm of healthy and demented elderly people has been demonstrated by application of a variety of potent modulators of the circadian timing system, like bright light (Campbell et al., 1993, Hohagen et al., 1994, Lovell et al., 1995, Mishima et al., 1994, Murphy and Campbell, 1996, Okawa et al., 1989, Satlin et al., 1992, Van Someren et al., 1997a), melatonin (Garfinkel et al., 1995, Haimov et al., 1995, Hughes et al., 1998, Mishima and Hishikawa, 1997, Singer et
Acknowledgements
Our research on chronobiological treatment of age-related sleep disturbances is supported by ZorgOnderzoek Nederland (ZON), The Hague (Prevention Project 2830030), NWO, The Hague (Project Successful Aging 014-90-001), Philips Lighting, Braun, Auping, Sarstedt and Bühlmann.
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