Melatonin and Bright-Light Treatment for Rest–Activity Disruption in Institutionalized Patients with Alzheimer's Disease

Autor: Erin Hubbard, Judy Mastick, Robert L. Burr, Eus J.W. Van Someren, Jay S. Luxenberg, Glenna A. Dowling, Bruce A. Cooper
Rok vydání: 2008
Předmět:
Zdroj: Journal of the American Geriatrics Society. 56:239-246
ISSN: 1532-5415
0002-8614
DOI: 10.1111/j.1532-5415.2007.01543.x
Popis: With Alzheimer’s disease (AD), nighttime sleep is severely fragmented, and daytime activity is disrupted by multiple naps. Leading theories that suggest possible etiologies for the rest–activity disruption include neurological deterioration that underlies the AD process and decreased exposure to external zeitgebers that influence circadian rhythms (e.g., bright light).1 Pharmacological treatments for nighttime sleep disruption have proven only minimally effective and are often associated with unacceptable side effects that are particularly problematic in AD, because sedative medications worsen cognition and contribute to fall risk.1,2 Disturbances in the rest–activity rhythm negatively affect quality of life and are one of the primary reasons caregivers seek institutionalization of patients with AD.3,4 Patients with socially unacceptable rest–activity rhythms (i.e., active during the night and asleep during the day) pose challenges for professional and lay care providers. In an institutional environment, patients experiencing rest–activity disruption can disturb other residents at night. Daytime somnolence also prevents participation in activities and social interaction.5 Exposure of the eyes to light of sufficient intensity and duration at the appropriate time of day can have profound effects on the quality, duration, and timing of sleep. The retinohypothalamic tract mediates the effect of light on the brain, and the daily light–dark cycle is the primary synchronizer responsible for entrainment of circadian rhythms to the 24-hour day. In an institutional environment, where light levels tend to be low, residents may not be exposed to sufficient bright light to entrain to the 24-hour day.6 Therapeutic exposure to bright light has been shown to alter rest–activity rhythms. Results from earlier phases of this study indicated that morning bright-light exposure (9:30–10:30 a.m.) for 10 weeks did not induce an overall improvement in measures of sleep or rest–activity rhythm, although subjects with aberrant timing of their rest–activity rhythm showed significant improvement in rhythm stability and amplitude.7 Subjects who received morning (9:30–10:30 a.m.) or afternoon (3:30–4:30 p.m.) bright-light exposure for 10 weeks were subsequently compared with a control group, and significant stabilization of the rest–activity rhythm acrophase was found in subjects who received bright light.8 Other investigators have reported positive effects of bright light on nighttime sleep time and circadian rhythm variables in subjects with dementia.9–14 In summary, although the appropriate intensity, duration, and timing of exposure to light has not been established, research results indicate that bright light can be an effective treatment strategy for rest–activity disruption in subjects with AD. Retinal neurons respond to stimuli from the light–dark cycle and project, through the retinohypothalamic tract, to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, which acts as a pacemaker. The light–dark cycle entrains the pacemaker and its outputs, including melatonin secretion.13,15 The pacemaker thus regulates the pineal gland’s timed secretion of the neurohormone melatonin, which in turn feeds back on melatonin receptors in the SCN. This feedback may be attenuated with older age because of a reduction in serum melatonin concentration and a shift in the melatonin secretion rhythm.15–17 Melatonin secretion is even lower in patients with AD, and this decrease is evident in the early stages of the disease.16,18–20 A further attenuation of the functional feedback signal of melatonin to the SCN in AD may result from the decrease in SCN melatonin receptors.21 Exogenous administration of melatonin in the morning delays circadian rhythms, and administration in the evening advances circadian rhythms.15 Nighttime melatonin administration has also been shown to act as a soporific, increasing sleep propensity, sleep efficiency, and daytime alertness and decreasing sleep onset latency and number of nighttime awakenings.22,23 In patients with dementia, exogenous melatonin administration has been shown to improve sleep in some studies but not in others. In two community-based studies using doses of 2.5 and 10 mg of melatonin and 6 mg of slow-release melatonin, there were no significant effects on nighttime sleep variables.24,25 In nursing home subjects, 6-mg melatonin treatment resulted in better sleep and less sundowning,26 and 1 to 3 mg melatonin resulted in less daytime sleepiness and sundowning but no improvement in nighttime sleep.27 Melatonin is considered to be a safe and nontoxic molecule. In healthy elderly people, low doses (0.2–2 mg) reportedly did not produce improvement in sleep measures, but a higher dose (50 mg) produced a sleep benefit with no adverse effects.24 One study found that 5 mg administered over 1 week trended toward improving sleep in subjects with Parkinson’s disease.28 Few side effects have been observed with low-dose melatonin (≤10 mg). None were noted during the pilot study (n = 8)28 or the subsequent larger study (n = 40).29 Another study24 found in its large sample (n = 157) no difference between tolerability of melatonin and that of placebo. Long-term side effects or interactions of melatonin with other drugs are not known.30 Possible effects of exogenous melatonin in humans include antioxidant properties, drowsiness, reduced glucose tolerance, an increase in peripheral but not cerebral blood flow, and reduction in blood pressure.31–34 Treatment with simultaneous bright light and melatonin in subjects with dementia has also been studied. One study35 reported on motor restless behavior in institutionalized subjects who received bright-light therapy in combination with 2.5 mg of melatonin and bright-light therapy in combination with placebo. Subjects who received melatonin became more aggressive and exhibited more disturbed behavior than subjects who received the placebo, who exhibited less restlessness and better cooperation. In summary, the results of previous studies on the effects of light and melatonin treatments for sleep disruption in dementia have been equivocal, and treatment durations have been short (a few weeks) and sample sizes small. The purpose of this study was to investigate the effects of bright light and bright light plus melatonin as zeitgebers to strengthen input to the circadian system on actigraphic estimates of night sleep time, daytime activity, day:night sleep ratio, and rest–activity rhythm.
Databáze: OpenAIRE
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