Sleep Disturbances and Comorbidities
Phyllis C. Zee
Alon Y. Avidan
Sleep disorders are common in the general population, but certain populations such as older adults, women, and patients with comorbid medical, psychiatric and neurologic disorders are at increased risk. In this chapter, we highlight the need to identify sleep disorders in these populations and provide examples of some of the more common medical and neurologic disorders that are often associated with sleep disturbances. The association between insomnia and psychiatric disorders is discussed in Chapter 13.
OLDER ADULTS
The geriatric patient population is growing very rapidly in the United States and around the world. In the year 2000, 34 million people in the United States were older than 65 years. By the year 2025, this number is expected to almost double to 62 million (1). In light of this fact, geriatricians and other health care providers need to manage an increased number of sleep disturbances, which increase with aging. Sleep-disordered breathing is one of these conditions. Despite reports that older adults sleep for about 7 hours per night, they frequently experience increased sleep fragmentation, decreased sleep efficiency, reduced quality of sleep, and decreased slow-wave sleep (2,3). These changes may be related to underlying age-related neuronal loss as well as a disruption of the suprachiasmatic circadian generator. Older adults experience poor sleep quality, which can exacerbate poor health and cognitive disturbances, and increase mortality (2).
WOMEN
Complaints of sleep disturbance are more prevalent among women than men across the entire lifespan (4,5). Alterations in the hormonal environment during the various phases of a woman’s life, from menstruation (6) and pregnancy (7) to menopause (8) likely contribute to insomnia in women.
Among women, there is a sharp rise in the prevalence of insomnia of approximately 40% during the peri- and postmenopausal periods (8,9). Although sufficient data exist that sleep quality is decreased with menopause, less is known regarding the underlying pathophysiology of insomnia in this population. In addition to hormonal changes, hot flashes, depression, anxiety, and sleep disorders such as primary insomnia, restless legs syndrome (RLS) and sleep apnea have been proposed as causes of sleep disturbance during menopause (4,10). The prevalence of obstructive
sleep apnea (OSA) increases significantly after the time of menopause (11), and hormone replacement therapy has been shown to decrease the risk of OSA. Reduction in 17-OH progesterone, progesterone, and estrogen were associated with increased sleep-disordered breathing in women with daytime sleepiness (12).
sleep apnea (OSA) increases significantly after the time of menopause (11), and hormone replacement therapy has been shown to decrease the risk of OSA. Reduction in 17-OH progesterone, progesterone, and estrogen were associated with increased sleep-disordered breathing in women with daytime sleepiness (12).
The importance of sleep-disordered breathing as an etiology of poor sleep quality in postmenopausal women is now well-documented (13, 14 and 15). A recent analysis of the Wisconsin Sleep Cohort data showed that menopause was an independent risk factor for sleep apnea-hypopnea (15). Consideration of the many potential causes and treatments of sleep disruption provides an excellent opportunity to improve health and quality of life in this population at high risk for insomnia.
SLEEP AND MEDICAL DISORDERS
Sleep disorders are often comorbid with medical conditions and negatively affect health, mood, and quality of life. Increasing evidence points to a bidirectional relationship between sleep and health, so that sleep disturbances contribute to the development or increase in severity of various medical disorders, and these same disorders result in poor sleep quality (16,17). Patients with chronic pain (e.g., arthritis, fibromyalgia), gastrointestinal (GI) disorders (e.g., gastroesophageal reflux disease [GERD]), cardiovascular disorders (e.g., coronary heart disease, congestive heart failure [CHF], hypertension), pulmonary disorders (e.g., chronic obstructive pulmonary disease [COPD], asthma), and metabolic disorders (e.g., obesity, diabetes) are at increased risk for disturbed sleep (18,19). Furthermore, many of the medications used to treat these conditions can also cause insomnia or daytime sleepiness.
Cardiovascular Disease
Sleep disturbance, especially chronic partial sleep loss, has been linked to problems with the cardiovascular system, including heart attack, irregular heartbeat, and stroke. Several epidemiologic surveys show a strong association between sleep complaints or shortened sleep durations and cardiovascular disease (20, 21 and 22). One study of Japanese workers found that individuals who slept less than 5 hours a night had a threefold increased risk of heart attacks (23).
Patients with coronary heart disease have more complaints of disturbed sleep than patients without coronary heart disease (24, 25 and 26). Sleep-disordered breathing has been shown to increase the risk of cardiovascular disease and stroke (27,28). Previous data have shown associations between OSA and cardiovascular morbidity, including systemic and pulmonary hypertension, left ventricular dysfunction, coronary artery disease, arrhythmias, CHF, and coronary heart disease (29,30). Potential mechanisms mediating hypertension include enhanced chemoreceptor sensitivity inducing excessive daytime sympathetic vasoconstrictor activity (29). There is some evidence to indicate that the increased vascular risk may be related to inflammation. For example, C-reactive protein (CRP) increases under both total and chronic partial sleep deprivation conditions (31) and has been found to be elevated in patients with OSA (32). Sleep disturbances are also common in patients with CHF (19). Sleep complaints include difficulty falling asleep as well a frequent nocturnal arousals, often associated with nocturnal dyspnea. Patients with CHF have a high prevalence of sleep-disordered breathing of the obstructive and central types (33). It has long been recognized that Cheyne-Stokes respirations (central sleep apneas) is a common cause of nocturnal dyspnea in CHF (34). Th erefore, optimizing the treatment of CHF and sleep-disordered breathing can improve sleep in patients with CHF (26).
Metabolic Disorders
Sleep is an important modulator of appetite and metabolism. Shortened sleep duration has been shown to alter leptin and ghrelin levels, which in turn stimulate appetite and may in part explain the association between increased weight and short
sleep duration (35,36). These findings are particularly relevant in modern societies, where chronic sleep restriction is common and food is readily available 24-7.
sleep duration (35,36). These findings are particularly relevant in modern societies, where chronic sleep restriction is common and food is readily available 24-7.
Sleep disturbances are common among individuals with diabetes. When compared to nondiabetics, patients with diabetes reported higher rates of insomnia and excessive daytime sleepiness (37,38). As much as 71% of this population report poor sleep quality (39). A number of factors contribute to sleep complaints in patients with diabetes. It has also been postulated that in patients with type I diabetes, rapid changes in glucose levels during sleep cause awakenings and complaints of insomnia (40). For individuals with adult-onset diabetes, sleep disturbances may be related to obesity and obesity-related sleep disorders such as OSA (41). Sleep-disordered breathing correlates highly with obesity in the diabetic population (41). However, independent of obesity, OSA is associated with impaired glucose tolerance, insulin resistance, and hypertension (41, 42 and 43). In addition, there is a correlation between the severity of sleep apnea and the severity of impaired glucose metabolism, insulin resistance, and diabetes (43,44).
Other common sources of disturbed sleep in diabetics include chronic discomfort or pain associated with diabetic peripheral neuropathy and RLS (45). Chronic pain, restless legs, and periodic leg movements can cause or exacerbate complaints of difficulty falling asleep and staying asleep (46). A thorough assessment of sleep quality and treatment of specific sleep disorders, such as sleep apnea and restless legs, can improve the management of metabolic disorders.
Respiratory Disorders
Sleep-disordered breathing (primarily in the form of OSA) is often seen in patients with COPD. Therefore, a large number of patients are likely to have the “overlap syndrome” of having both OSA and COPD, which can result in more severe nocturnal hypoxemia than either condition alone (47). Sleep quality is often poor in patients with COPD (48). Impairment of pulmonary function was associated with decreased total sleep time and decreased sleep efficiency (49). Sleep can have significant negative effects on respiration in patients with respiratory compromise, resulting in hypoxemia and hypercapnia (50), which in turn can disturb sleep. Chronic dyspnea and sleep-related hypoxemia likely contribute to the disturbed sleep of patients with COPD. Therefore, therapies such as bronchodilators and nocturnal oxygen supplementation may also improve sleep quality (33,50). In addition to impaired pulmonary function and nocturnal hypoxemia, OSA and other sleep disorders such as insomnia and RLS are common in older patients with COPD and likely contribute to the higher prevalence of sleep complaints in this population (48).
Adults with asthma have more complaints of restless sleep and sleepiness than those without asthma (51,52). Sleep can be disrupted by asthma attacks, which occur more frequently in the second half of the night, during REM sleep (52,53). The presence of OSA and gastroesophageal reflux should also be considered in patients with nocturnal worsening of asthma (33). Therefore, all patients with asthma should be asked about their sleep quality and symptoms of OSA, which can further disrupt sleep and cause hypoxemia during sleep.
Gastrointestinal Disorders
Patients with GI disorders have a higher prevalence of sleep disorders as compared to the general population (54)
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