Sleep Disorders and Sleep Deprivation An Unmet Public Health Problem (2006) / Chapter Skim
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3 Extent and Health Consequences of Chronic Sleep Loss and Sleep Disorders
3 Extent and Health Consequences of Chronic Sleep Loss and Sleep Disorders
Pages 55-136
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From page 55... ...
This chapter focuses on manifestations and prevalence, etiology and risk factors, and comorbidities of the most common sleep conditions, including sleep loss, sleep-disordered breathing, insomnia, narcolepsy, restless legs syndrome, parasomnias, sleep-related psychiatric disorders, sleep-related neurological disorders, sleep-related medical disorders, and circadian rhythm sleep disorders.
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From page 56... ...
The cumulative effects of sleep loss and sleep disorders have been associated with a wide range of deleterious health consequences including an increased risk of hypertension, diabetes, obesity, depression, heart attack, and stroke. This chapter focuses on the most common sleep conditions, including sleep loss, sleep-disordered breathing, insomnia, narcolepsy, restless legs syndrome (RLS)
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. Etiology and Risk Factors The causes of sleep loss are multifactoral.
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, of whom there is a growing number of night shift workers suffering chronic sleep loss and disruption of circadian rhythms (Harma et al., 1998; Drake et al., 2004)
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The studies discussed in this section suggest that sleep loss (less than 7 hours per night) may have wide-ranging effects on the cardiovascular, endocrine, immune, and nervous systems, including the following: · Obesity in adults and children · Diabetes and impaired glucose tolerance · Cardiovascular disease and hypertension · Anxiety symptoms · Depressed mood · Alcohol use Many of the studies find graded associations, insofar as the greater the degree of sleep deprivation, the greater the apparent adverse effect (although the difference may not reach statistical significance)
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The U-shaped association also applies to other health outcomes, such as heart attacks. The impact of sleep loss diminishes with age.
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. Sleep Loss Is Associated with Diabetes and Impaired Glucose Tolerance Two large epidemiological studies and one experimental study found an association between sleep loss and diabetes, or impaired glucose tolerance.
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. The association between sleep loss and diabetes or impaired glucose tolerance may mediate the relationship between sleep loss and cardiovascular morbidity and mortality, as discussed below.
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Experimental data, showing that acute sleep loss (3.6 hours sleep) for one night results in increased blood pressure in healthy young males, may provide a biological mechanism for the observed associations between sleep loss and cardiovascular disease (Tochikubo et al., 1996; Meier-Ewert et al., 2004)
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. The most effective treatment for sleep loss is to sleep longer or take a short nap lasting no more than 2 hours (Veasey et al., 2002)
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. Modafinil is the only FDA-approved drug for shift work sleep disorder, although it is not approved for sleep loss.
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. Obstructive Sleep Apnea Causes Hypertension OSA causes chronic elevation in daytime blood pressure (Young et al., 2002a; Young and Javaheri, 2005)
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The latest efforts by the American Academy of Sleep Medicine (2005) have attempted to apply evidence-based guidelines to the recommendations.
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. Further, evidence from pediatric studies indicate elevations in systemic blood pressure during both wakefulness and sleep in children with sleep apnea (Amin et al., 2004)
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. Obstructive Sleep Apnea Is Associated with Cardiovascular Disease and Stroke Epidemiological studies reveal an association between OSA and cardiovascular disease, including arrhythmias (Guilleminault et al., 1983)
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, providing temporal associations in support of OSA playing a causal role in the development of heart diseases. As will be discussed in the next section, OSA is associated with glucose intolerance and diabetes, both of which are independent risk factors for cardiovascular disease.
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. Obstructive Sleep Apnea Is Associated with Impaired Glucose Tolerance and Diabetes OSA is associated with impaired glucose tolerance and insulin resistance, according data from several studies (Ip et al., 2002; Punjabi et al., 2002)
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. Obstructive Sleep Apnea May Contribute to Obesity Up to 40 percent of people who are morbidly obese have OSA (Vgontzas et al., 1994)
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. The pathophysiological roles of these risk factors are not well understood, although evidence suggests that fat deposition in the upper airways, which is more likely in males, contributes to the physical narrow TABLE 3-1 Risk Factors for Obstructive Sleep Apnea Risk Factor Reference Obesity and BMI greater than 25 kg/m2 Grunstein et al., 1993 Male gender Strohl and Redline, 1996; Kapsimalis and Kryger, 2002; Shepertycky et al., 2005 Familial association Guilleminault et al., 1995; Pillar and Lavie, 1995; Redline et al., 1995; Buxbaum et al., 2002 Alcohol consumption Taasan et al., 1981 Cranial facial structure Ferguson et al., 1995 High and narrow hard palate, elongated soft palate, small chin, and abnormal overjet Enlargement of the tonsils Behlfelt, 1990 Lesions of the autonomic nervous Mondini and Guilleminault, 1985; Rosen et al., system 2003 Race: African Americans, Mexican Schmidt-Nowara et al., 1990; Redline et al., Americans, Pacific Islanders, and 1997; Li et al., 2000 East Asians
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, but several well-designed, population-based studies failed to find an association (Ancoli-Israel et al., 1996; Lindberg et al., 1998; Kripke et al., 2002) , except in one subgroup of patients below age 60 with both snoring and excessive daytime sleepiness.
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. Evidence of CPAP's efficacy for alleviating daytime sleepiness comes from randomized controlled trials and meta-analysis (Patel et al., 2003)
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Etiology and Risk Factors The precise causes of insomnia are poorly understood but, in general terms, involve a combination of biological, psychological, and social factors. Insomnia is conceptualized as a state of hyperarousal (Perlis et al., 2005)
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Other risk factors for insomnia include family history of insomnia (Dauvilliers et al., 2005) , stressful life styles, medical and psychiatric disorders, and shift work (Edinger and Means, 2005)
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Sleep restriction therapy A method to curtail time in bed to the actual sleep time, thereby creating mild sleep deprivation, which results in more consolidated and more efficient sleep. Relaxation training Clinical procedures aimed at reducing somatic tension (e.g., progressive muscle relaxation, autogenic training)
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One is shorter rapid eye movement (REM) latency (a shorter period of time elapsing from onset of sleep to onset of REM sleep)
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. Normally, the transition from waking to NREM sleep is associated with decreases in these frontal lobe regions.
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. Insomnia and Psychiatric Disorders As mentioned above insomnia is associated with depression, acting as both a risk factor and a manifestation (Ford and Kamerow, 1989; Livingston et al., 1993; Breslau et al., 1996; Weissman et al., 1997; Chang et al., 1997; Ohayon and Roth, 2003; Cole and Dendukuri, 2003)
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is also not known. NARCOLEPSY AND HYPERSOMNIA Manifestations and Prevalence Narcolepsy and idiopathic hypersomnia are characterized by a clinically significant complaint of excessive daytime sleepiness that is neither explained by a circadian sleep disorder, sleep-disordered breathing, or sleep deprivation, nor is it caused by a medical condition disturbing sleep (AASM, 2005)
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Mean sleep latency of less than 8 minutes and two or more sleep onset rhythmic eye movement periods is diagnostic for narcolepsy. The MSLT must always be preceded by nocturnal sleep polysomnography to rule out other causes of short MSL or sleep onset rhythmic eye movement periods such as OSA, insufficient sleep, or delayed sleep phase syndrome.
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The second subtype of idiopathic hypersomnia, idiopathic hypersomnia without long sleep time, is characterized by a complaint of excessive daytime sleepiness and a short mean sleep latency on the MSLT. In most sleep disorders clinics with experience in this area, approximately one-third of hypersomnia cases are diagnosed with this condition (Aldrich, 1996)
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. Etiology and Risk Factors Similar to other sleep disorders, little is known about the pathophysiology and risk factors for narcolepsy and hypersomnia.
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unrefreshing nocturnal sleep Idiopathic MSLT: short mean Probably common, Unknown, probable hypersomnia sleep latency, less unknown heterogeneous with normal than two SOREMPs; prevalence etiology sleep length normal nightly sleep amounts (less than 10 hours) Periodic hyper- Recurrent (more than Rare, probably less Unknown, probable somnia (includes 1 time per year)
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In narcolepsy with cataplexy, pharmacological treatment for daytime sleepiness involves modafinil or amphetamine-like stimulants, which likely act through increasing dopamine transmission. Cataplexy and abnormal REM sleep symptoms, sleep paralysis and hallucinations, are typically treated with tricyclic antidepressants or serotonin and norepinephrine reuptake inhibitors.
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. Typically the arousals occur during the first 60 to 90 minutes of sleep and do not cause full awakenings, but rather partial arousal from deep NREM sleep.
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Sleep-related Hallucinatory images that occur at sleep onset or on awakening hallucinations NOTE: NREM, non-rapid eye movement; REM, rapid eye movement; SWS, slow-wave sleep. SOURCES: Halasz et al.
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. Disorders Associated with REM Sleep Rapid Eye Movement Sleep Behavior Disorder REM sleep behavior disorder is characterized by a complex set of behaviors that occur during REM sleep, including mild to harmful body movements associated with dreams and nightmares (AASM, 2005)
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. Etiology and Risk Factors There is limited information regarding the etiology of sleep disorders associated with Alzheimer's disease and other conditions that cause dementia.
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Sleep disturbances associated with Parkinson's disease include difficulty falling asleep, nocturnal akinesia, altered sleep architecture, abnormal motor activity, periodic limb movements, REM sleep behavior disorder (see above) , and disturbed breathing.
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Sleep, sleep deprivation, and seizure activity are tightly intertwined. After stroke and Alzheimer's disease, epilepsy is the third most common neurological disorder in the United States, with incidence between 1.5 to 3.1 percent (Shouse and Mahowald, 2005)
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Etiology and Risk Factors Risk factors for sleep-related epilepsy include stress, sleep deprivation, other sleep disorders, and irregular sleep-wake rhythms. The etiologies for nocturnal seizures are not clearly understood.
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Following a stroke an individual's sleep architecture is often altered, causing a decrease in the total sleep time, REM sleep, and SWS (Broughton and Baron, 1978)
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, possibly resulting in a baby being unable to wake up in response to troubled breathing. Concordantly, risk factors attributed to SIDS typically relate to an infant's ability to breathe easily while sleeping.
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, suggesting that there may be common genetic risk factors for both conditions. Finally, general measures of poor health form the final category of risk factors.
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. Individuals with RLS often experience periodic limb movements; however, periodic limb movement disorder (see below)
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. Although associated with some adverse effects, administration of L-dopa significantly reduces symptoms of RLS and periodic limb movements that occur throughout the night (Brodeur et al., 1988)
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Periodic limb movements are very common in RLS, occurring in 80 to 90 percent of individuals. It is also observed in individuals with narcolepsy, REM sleep behavior disorder (Folstein et al., 1975)
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. However, it is not known if hypocretin and other genes that regulate the circadian rhythms are affected by acute or chronic pain.
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Bacterial Infections and Sleep Bacterial infections typically cause an increase in the total time spent in SWS and a decreased duration of REM sleep (Toth, 1999; Toth and Opp, 2002)
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Individuals spend increased time in SWS during the second half of night (Darko et al., 1995) and suffer from frequent arousals and decreased time in REM sleep (Norman et al., 1990)
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However, many medical therapies have iatrogenic effects on sleep-wake regulatory systems causing disturbed sleep, daytime sleepiness, and other related side effects. Treatments for Cardiovascular Disease Cardiovascular diseases, sometimes associated with sleep-related breathing disorders (Peters, 2005)
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. Treatments for Renal Disease RLS, periodic limb movement disorder, sleep apnea, and excessive daytime sleepiness affect up to 70 percent of patients with end-stage renal disease receiving treatment with hemodialysis (Parker et al., 2000; Parker, 2003)
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, including daytime sleepiness and sleep disturbances (Raison and Miller, 2001; Capuron et al., 2002)
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CIRCADIAN RHYTHM SLEEP DISORDERS Circadian rhythm sleep disorders arise from chronic alterations, disruptions, or misalignment of the circadian clock in relation to environmental cues and the terrestrial light-dark cycle. The 2005 update of the International Classification of Sleep Disorders designated nine different circadian disorders, including delayed sleep phase type, advanced sleep phase type, nonentrained sleep-wake type, irregular sleep-wake type, shift work type, and jet lag type (Box 3-3)
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. The following sections will describe two of the nine more common types of circadian rhythm sleep disorders, delayed sleep phase type and advanced sleep phase type.
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. Etiology and Risk Factors Night shift workers may be at higher risk for delayed sleep phase syndrome due to irregular circadian entrainment (Santhi et al., 2005)
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. Etiology and Risk Factors The causes of this syndrome are not known; however, as with delayed sleep phase type, biological and environmental factors likely contribute to the onset of advanced sleep phase type.
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1992. The delayed sleep phase syndrome: Clinical and investigative findings in 14 subjects.
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2003. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference.
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2003. Clinical effects of sleep fragmentation versus sleep deprivation.
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1994. Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: Effect of continuous positive airway pressure treatment on insulin responsiveness.
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1998. Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson's disease.
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2005. Chronic sleep deprivation.
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2002. REM sleep behavior disorder and REM sleep without atonia in Parkinson's dis ease.
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1998. Combined effects of shift work and life-style on the prevalence of insomnia, sleep deprivation and daytime sleepi ness.
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gene with delayed sleep phase syndrome. Neurogenetics 4(3)
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1999. Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans.
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2000. Sleep loss and daytime sleepiness in the general adult population of Japan.
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1998. Blood pressure in children with obstructive sleep apnea.
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2005. Restless legs syndrome and periodic limb movements during sleep.
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1999. Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea.
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In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine.
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2003. Efficacy of enhanced evening light for advanced sleep phase syndrome.
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1988. Prevalence of delayed sleep phase syndrome among adolescents.
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1997. REM sleep behavior disorders in multiple system atrophy.
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1995. Delayed sleep phase syndrome: A review of its clinical as pects.
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1990. Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome.
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1999. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure.
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2001. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.
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2002. Sleep loss and fatigue in residency training: A reappraisal.
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1996. Effects of light and chrono therapy on human circadian rhythms in delayed sleep phase syndrome: Cytokines, corti sol, growth hormone, and the sleep-wake cycle.
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2005. Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome.
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