Epidemiology of Sleep Disorders

Epidemiology of Sleep Disorders Markku Partinen and Christer Hublin Abstract Every day one third or more of the population suffers from some sleep disturbance and/or from abnormal daytime sleepiness. At least 10% of the population suffers from a sleep disorder that is clinically significant and of public health importance. Insomnia is the most common sleep disorder, followed by sleep-disordered breathing and restless legs syndrome. Sleep disorders are interrelated with medical and psychiatric disorders, such as arterial hypertension, cardiovascular and cerebrovascular diseases, morbid obesity, diabetes, metabolic syndrome, and depression. Many gender, socioeconomic, and also ethnic differences exist; and more epidemiologic and genetic epidemiologic studies are needed to understand reasons for these differences. In the 1980s, the large epidemiologic studies on sleep disorders were based on the 1979

Although sleep disorders are very common, rigorous epidemiologic studies in this field are fairly recent, in part because the discipline of sleep medicine is recent. In this chapter we present epidemiologic data important in the practice of sleep medicine. There are several excellent books of epidemiologic methods that are recommended.3-6

SLEEP DURATION Sleep duration is highly individual in all age groups, and it is clearly dependent on age. In the United States the relationship between age and the average sleep time is U-shaped, with a minimum 7.9 hours at age 45 to 54 years and a maximum (9.0 hours) at age 75 years or older.7 In addition to sleep disorders (e.g., insomniacs among short sleepers and hypersomniacs among long sleepers), there are also healthy subjects in the extreme groups: a few percent of the populations are so-called natural short sleepers or natural long sleepers (ICSD-2).2,8 Sleep duration can be considered as a lifestyle factor that is modulated by several background factors and by genotype. In a Finnish general-population study the most important and statistically independent determinants of short and long sleep duration were gender, physical tiredness, sleep problems, marital status, main occupation, and physical activity, but these accounted for only 16% of the variance in sleep duration.9 In the United States the largest reciprocal relationship to sleep was found for work time, followed by travel time, and only shorter than average (<7.5 hours) sleepers spent more time socializing, relaxing, and engaging in leisure activities, whereas both short (<5.5 hours) and long (≥ 8.5 hours) sleepers watched more television than average sleepers.7 The same study showed also significant differences in sleep length between weekdays and weekend (longest on Sunday [9.6 hours] and shortest on Friday [8.0 hours]). The effect of genetic aspects has been assessed in large twin cohorts. In the Finnish cohort, representative of the general population, a significant 694

Chapter

61

sleep disorders classification. In 1990,1 a new International Classification of Sleep Disorders (ICSD) was published. Its revised version from 20052 is now commonly used in sleep medicine. For statistical purposes the International Classification of Diseases, 10th revision (ICD-10) published by the World Health Organization, is commonly used especially in Europe and Asian countries. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), published by the American Psychiatric Association, also includes criteria for diagnosing sleep disorders. The DSM-IV criteria have been commonly used especially in studies of insomnia. From the public health and clinical viewpoints, the most important problems related to sleep–wake disorders are insomnia, sleep deprivation, sleep-related breathing disorders, restless legs syndrome, excessive daytime sleepiness, and parasomnias.

hereditary effect was found on sleep length (overall heritability estimate h2 = 0.44) and sleep quality (h2 = 0.44).10 Similarly, in an Australian cohort, genetic influences accounted for at least 33% of the variance in sleep quality and sleep disturbance.11 There seem to be differences between populations and countries in the mean duration of sleep and trends in them. Among students from 24 countries, sleep was shortest in Japan (6.2 hours in men and 6.1 hours in women), and longest in Bulgaria (7.8 and 8.0 hours, respectively).12 In the United States the self-reported modal of sleep duration has been estimated to be about 8 hours in the 1960s,13 but more recent Gallup surveys have yielded estimates of about 7 hours or even less (National Sleep Foundation, 2005). However, based on reanalysis of all population-based surveys with information on sleep duration (>440,000 persons) in Finland from 1972 to 2005 the mean sleep duration was shortened only 18.3 minutes to about 7.3 hours.9 The same study showed that sleep was shortest and sleep complaints were most frequent among middle-aged employees. It is possible that changes in society (e.g., “24/7”) and working life (e.g., increase in irregular working hours and stress) have an effect on sleep and contribute to insufficient sleep, leading to fatigue and sleepiness during awake times.14 In Sweden, 12% of adults had persistent and considerable chronic sleep loss. In subjects without sleeping difficulties, the most common cause of insufficient sleep was too little time for sleep.15 In Finland, the prevalence of insufficient sleep, defined as a difference of at least 1 hour between the reported need for sleep and obtained sleep length, was 20.4% (16.2% in men; 23.9% in women). Almost half of those with insufficient sleep continued to have it 9 years later. One third of the liability to chronic insufficient sleep was attributed to genetic influences.16 Sleep duration is associated with different health outcomes. The first report was by Hammond in 1964, in



which there was a U-shaped curve between sleep length and risk of mortality, being lowest in those sleeping 7 hours.13 In the early 1980s a U-shaped curve was also found between sleep length and coronary heart disease.17 Later, more than 20 studies have been published on this topic, and the association between sleep length and mortality/ morbidity has been confirmed in many of them.18 The increases in risk have mostly been around 12%. There are also two studies with more than one assessment of sleep behavior,19,20 which may be of importance because in the other studies sleep length and sleep quality changed in one third during 6 years.20 The cause(s) and mechanism(s) of the association are poorly understood. Association with short sleep and sleep deprivation may be linked to dysfunction of the restorative function of sleep. Long sleep may be a consequence of a dysfunction/morbidity (e.g., increased levels of cytokines).21,22 Further long-term cohort studies enable better inferences about causal relationships. It is also important to study natural short and natural long sleepers who have had the same sleeping habits since an early age. Sleep length has also other interesting and important, yet complex associations. In a recent meta-analysis of short sleep and obesity (45 studies with more than 630,000 participants) there was a significantly increased risk both in children (pooled odds ratio [OR] = 1.89) and in adults (OR = 1.55) but the difficulty of causal inference was noted.23 On the other hand, in a clinical review, Marshall and coworkers considered the evidence in adults to be insufficient.24 The association between sleep length and type 2 diabetes has been found in several studies, indicating a 35% to 100% increase in risk for short sleepers25-27 and a 50% to 200% increase for long sleepers.26,27 There is some evidence about an association between sleep length and hypertension: in short sleepers, risks increased from 66%28 to 110%29; and in long sleepers, 19% to 30%28 increases have been reported. However, in some studies no significant association has been observed in elderly persons30 or after adjustment for known risk factors.31 In women, short and long sleep is associated with a 40% increase of risk of coronary heart disease.31,32

INSOMNIA AND USE OF HYPNOTIC AGENTS Insomnia is the most common sleep–wake-related complaint, and sleeping pills are among the most commonly prescribed drugs in clinical practice, especially at the primary health care level.32a Based on a large number of published epidemiologic studies we can generalize that the prevalence of symptoms of insomnia is about 30% among adults (Tables 61-1 and 61-2), and the prevalence of specific insomnia disorders varies between 5% and 10%.33,34 Symptoms of insomnia often persist, and earlier occurrence of insomnia increases the probability of insomnia in later life.35,36 There is some evidence that the occurrence of insomnia has increased during the past 30 years.9 Insomnia can be a symptom of an underlying problem with dozens of causes, or it can be a primary disease. Different questionnaires usually contain items about trouble falling asleep, trouble staying asleep, nocturnal awakenings, early morning awakening, and the use of hypnotic agents. The

CHAPTER 61  •  Epidemiology of Sleep Disorders  695

number of urinary voids per night seems to be a good question. People remember easily how many times they wake because of the need to void. Waking up twice to void may not be bothersome. On the contrary, waking up twice or more without the need to void may reflect depression, brain hyperactivity, or some other underlying problem, and frequent (more than two times per night) nocturnal voiding may be a symptom of sleep apnea.37-39 The heterogeneity of the definitions and methods used is striking, but some clear trends can be seen. First, insomnia increases with age. About one third of subjects older than 65 years old have more or less continuous insomnia, although at very old age the levels may be lower. In Australia, insomnia was persistent in 16.2% of the communitydwelling population and 12.2% of the institutional residents. Altogether, 14.5% of the elderly subjects living in the community were using hypnotics regularly while the corresponding percentage was 39.7% among the institutional residents.40 In a large U.S. population–based study,41 the prevalence of insomnia was 7.5% and that of difficulty sleeping was an additional 22.4%. In children and adolescents, the prevalence of frequent insomnia is quite variable; in several studies, it is higher than 10%. In middle-aged populations, the frequency of longstanding insomnia seems to be around 10%. Trouble falling asleep seems to be the most common manifestation in younger age groups, whereas trouble staying asleep is the most frequent form of insomnia in middle-aged and elderly people.9,41-46 Second, there is a clear gender difference, with insomnia occurring about 1.5 times more often in women than in men; this is especially true in menopausal and postmenopausal women compared with middle-aged men. Third, seasonal differences, probably due to light exposure, can occur and the results are consistent in Nordic countries. In northern Norway, 41.7% of the women and 29.9% of the men had occasional insomnia.47 As a whole, complaints of insomnia were more common during the dark period of year than during other times of the year. In the Tromsø study, occurrence of insomnia during the midnight sun period (summer insomnia) decreased with age whereas the other seasonal types of insomnia increased with age.47 Fourth, comorbidity is very common. The association of psychiatric disorders, especially depression, with insomnia is well known. Primary insomnia and insomnia related to mental disorders are the two most common insomnia diagnoses listed in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).42 Insomnia is a frequent complaint among patients with different respiratory symptoms. In the study of Dodge and coworkers,, the prevalence of insomnia was 31.8% to 52.4% among adults with cough, dyspnea, or wheezing; among adults without respiratory symptoms, the prevalence was 25.8% to 26.2%.48 In a World Health Organization collaborative study, 25,916 primary health care attendees were evaluated (Üstün B, Worldwide Project on Sleep and Health; see www-websciences.org). Sleep problems were present in 27% of the patients. Of the patients with insomnia, 51% had a well-defined mental disorder according to the 10th edition of the Internal Classification of Diseases (ICD-10) that mainly included

696  PART II / Section 8  •  Impact, Presentation, and Diagnosis Table 61-1  Occurrence of Insomnia REFERENCE (COUNTRY) Saarenpää-Heikkilä et al.64 1995 (Finland) Tynjälä et al.65 1993 (Finland)

NO. SUBJECTS 574

40,202

AGE RANGE (YR)

DEFINITION

METHODS

OCCURRENCE (%)

School-age children (7-17)

Sleeplessness

Questionnaire

Often or always: 4 (m), 5 (f) Sometimes: 61 (m), 57 (f)

School-age children (11-16)

Inability to fall asleep twice a week

Questionnaire (in nine countries)

11-12 yr: 16.4-33.2 13-14 yr: 11.5-25.3 15-16 yr: 10.8-26.6

Partinen and Rimpelä66 1982 (Finland)

2016

Population sample (15-64)

Insomnia daily or several times

Telephone interview weekly

7 (m), 9 (f) 15-24 yr: 5 25-44 yr: 6 45-64 yr: 14

Ford and Kamerow67 1989 (USA)

7954

Population sample (18-65+)

Ever a period of ≥2 weeks with trouble falling asleep, staying asleep, or waking up too early

Direct structured interview using diagnostic interview schedule (DIS)

7.9 (m), 12.1 (f)

Population sample (18+)

During the past year, ever having a period of ≥2 weeks or more with trouble falling asleep, staying asleep, or waking

Direct structured interview using DIS67 as in Ford & Kamerow67

All types: 11.9 Uncomplicated: 4.9 Complicated: 3.6

Weissman et al.68 1997 (USA)

10,533

Dodge et al.48 1995 (USA)

1667

Population sample (18-65+)

Current trouble falling asleep, staying asleep, or waking up too early

Questionnaire and interview

18-44 yr: 22.8 (m), 30.0 (f) 45-64 yr: 31.5 (m), 43.8 (f) >64 yr: 36.4 (m), 47.6 (f)

Morgan and Clarke69 1997 (England)

1042

Primary care (65-80+)

Patients with sleeping problems often or all the time

Questionnaire

65-69 yr: 33.2 (m), 44.1 (f) 70-74 yr: 39.4 (m), 44.4 (f) 75-79 yr: 11.2 (m), 30.8 (f)

982

Population sample (18+)

Insomnia (DSM-IV)

Telephone survey using Sleep-EVAL

DSM-IV: 11.7 Any type: 37.6

3030

Population sample (20+)

Insomnia of any type

Interview at home

22.3 (m), 20.5 (f) 20-39 yr: 18.1 40-59 yr: 18.9 60+ yr: 29.5 No stress: 15.9 Stress: 25.8

Population sample (20-100)

Insomnia Difficulty sleeping

Questionnaire (PSG in 1741)

Insomnia: 7.5 Difficulty sleeping: 22.4

Ohayon and Partinen43 2002 (Finland) Kim et al.70 2000 (Korea)

Bixler et al.41 2002 (USA)

16,583

Li et al.71 2002 (Hong Kong)

9851

Population sample Chinese (18-65)

Insomnia, DSM Preceding month ≥3 per week

Telephone survey

Insomnia: 11.9% Women: 1.6 × P (men) Increase with age

Morin et al.46 2006 (Canada)

2001

Population sample (18-91)

Insomnia, DSM-IV & ICD-10, ≥3 nights/wk

Telephone survey

Symptoms of insomnia: 29.9 Insomnia syndrome: 9.5

DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th ed; f, female; m, male.



CHAPTER 61  •  Epidemiology of Sleep Disorders  697

Table 61-2  Occurrence of Symptoms of Insomnia Based on Different Types of Insomnia Complaints TROUBLE FALLING ASLEEP (%)

TROUBLE STAYING ASLEEP (%)

Questionnaire

1-2 nights/wk: 12.9 ≥3 nights/wk: 11.3

1-2 nights/wk: 6.0 ≥3 nights/wk: 6.5

Adolescents (13-15)

Interview

≥4 nights/wk: 9.1 (m), 10.0 (f)

≥4 nights/wk: 1.5 (m), 3.0 (f)

>4 nights/wk: 2.5 (m), 4.4 (f)

4972

Population sample (>14)

Telephone interview

Currently: 10.5 (m), 15.3 (f)

Currently: 16.4 (m), 24.8 (f)

Currently: 13.7(m), 17.8 (f)

Bixler et al.74 1979 (USA)

1006

Population sample (>18)

Sleep-EVAL questionnaire

Currently: 14.4 (about two thirds women)

Currently: 22.9 (about two thirds women)

Currently: 13.8 (about two thirds women)

Karacan et al.75 1983 (USA)

2347

Population sample (18-65+)

Interview

Often or always (no age effect): 6.0 (m), 11.2 (f)

Often or always Often or always (significant (significant increase with increase with age): 12.9 (m), age): 6.2 (m), 17.4 (f) 8.0 (f)

Ganguli et al.35 1996 (USA)

1050

Population sample (66-97)

Questionnaire

Sometimes or usually: 26.7 (m), 44.1 (f)

Sometimes or usually: 19.2 (m), 35.8 (f)

Sometimes or usually: 13.6 (m), 23.3 (f)

Blazer et al.76 1995 (USA)

3976

Population sample (≥65; EPESE)

Interview using a questionnaire

Blacks: 14.8 Whites: 16.3

Blacks: 19.9 Whites: 33.8

Blacks: 12.9 Whites: 16.0

Foley et al.77 1995 (USA)

9282

Population sample (≥65; EPESE)

Interview using a questionnaire

Most of the time: 19.2

Most of the time: 29.7

Most of the time: 18.8

Henderson et al.40 1995 (Australia)

869

Population sample (≥70)

Home interview, computer

Nearly every night over the previous 2 weeks: 5.1 algorithm

NA

Nearly every night over the previous 2 weeks: 2.6

Kim et al.70 2000 (Japan)

3030

Population sample (≥20)

Home interviews

7.0 (m) 9.4 (f) No stress: 4.1 Stress: 11.6

20-39 yr: 11.1 40-59 yr: 13.6 60+ yr: 22.6 No stress: 11.2 Stress: 18.3

20-39 yr: 5.1 40-59 yr: 6.7 60+ yr: 13.3 No stress: 6.0 Stress: 9.4

Ohayon and Partinen43 2002 (Finland)

982

Population sample (≥18)

Telephone survey using Sleep-EVAL questionnaire

≥3 nights/wk: 10.4 (m), 13.2 (f)

≥3 nights/wk: 30.2 (m), 33.0 (f)

≥3 nights/wk: 9.7 (m), 12.2 (f)

Li et al.71 2002 (Hong Kong)

9851

Population sample: Chinese (18-65)

Telephone survey Preceding month ≥ 3 nights/wk

≥3 nights/wk: 4.5 (4.1-5.0)

≥3 nights/wk: 6.9 (6.4-7.5)

≥3 nights/wk: 4.0 (3.6-4.4)

Morin et al.46 2006 (Canada)

2001

Population sample (18-91)

Telephone survey

≥3 nights/wk: 8.7 (7.4-9.9)

≥3 nights/wk: 6.4 (5.3-7.4)

≥3 nights/wk: 2.1 (1.5-2.8)

Gureje et al.78 2007 (Nigeria)

6752

Population sample (>18)

Face-to-face interviews

>2 wk/yr: 7.7

>2 wk/yr: 8.5

>2 wk/yr: 5.4

REFERENCE (COUNTRY)

NO. SUBJECTS

POPULATION (AGE RANGE, YR)

Blader et al.72 1997 (USA)

987

School-age children (5-12)

Morrison et al.73 1992 (Canada)

943

Ohayon et al.42 1997 (UK)

METHODS

EARLY MORNING AWAKENING (%)

EPESE, Established Populations for Epidemiologic Studes of the Elderly; f, female; m, male; NA, not applicable.

depression or anxiety, alcohol abuse, or both. Use of alcohol and over-the-counter medications to control insomnia is common. Also, somatic and psychological complaints as well as psychological stress are associated with a higher prevalence of insomnia.33,49-51 Fifth, social and occupational factors are important contributors to insomnia. Being unemployed or not married is associated with a higher prevalence of insomnia.14,52,53 In

a questionnaire survey of 6268 adults in 40 different occupations, 18.9% of bus drivers complained of having some or very much difficulty falling asleep. Among male executives and male physicians, the respective percentages were 3.7% and 4.9%. Disturbed nocturnal sleep was complained of the most often by male laborers (28.1% waking up at least three times a night) and female housekeepers (26.6%). Disturbed nocturnal sleep was rare among male physicians

698  PART II / Section 8  •  Impact, Presentation, and Diagnosis

(1.6%), male executives (7.4%), female head nurses (8.9%), and female social workers (9.4%).54 Symptoms of workrelated stress and mental exhaustion are associated with insomnia.46,55-57 Use of Hypnotics In a nationally representative probability sample survey of noninstitutionalized adults, 3161 people 18 to 79 years old were surveyed.58 Insomnia afflicted 35% of all adults during the course of 1 year. During the year before the survey, 2.6% of adults had used a medically prescribed hypnotic agent; 0.3% of all adults and 11% of all users of hypnotic agents reported using the medication regularly for 1 year or longer. When anxiolytic and antidepressant agents were excluded, 4.3% of adults had used a medically prescribed hypnotic for sleep and 3.1% had used an overthe-counter sleeping pill. In a reanalysis of several studies published in Finland between 1972-2005 (251,083 subjects) the prevalence figures concerning the use of sleeping medicine at least once a week among adult population did not show any clear trend of increase; the figures varied between 4% and 6% from 1982 to 2002.9 In Sweden, 10,216 members of the Swedish Pensioners’ Association were surveyed.59 Hypnotic agents were used by 13.5% of the men and 22.3% of the women. Of the men aged younger than 70 years, 7.9% were receiving such treatment; of those 70 to 80 years old, 14.4% were using hypnotic agents; and of those 80 years old or older, 21.8% were taking hypnotic agents (P < .0001). The corresponding frequencies among women were 15.0%, 23.0%, and 34.9%, respectively (P < .0001). Hypnotic agents are used by many institutionalized elderly subjects even without insomnia. This raises an ethical question because the chronic use of hypnotic agents is associated with excessive mortality rates.60 In a excellent meta-analytic study of risks and benefits of hypnotics among elderly persons the number needed to treat for improved sleep quality was 13 and the number needed to harm for any adverse event was 6.61 An excellent way of tracking the use of hypnotic medication of the population is to count unit defined daily doses (DDD) from the sales statistics. When one knows the assumed average dose per day for each drug, sales per year, and population of the country, one can calculate DDD per 1000 inhabitants per day. In Finland, for all hypnotic agents, the rate in 1994 was 38 DDD/1000 inhabitants/ day. In 2002 the rate had increased to 53.4 DDD/1000 inhabitants/day. Since that time the use of hypnotics has remained about the same. In 2007 the rate was 53.8 DDD/1000 inhabitants/day.62 Benzodiazepines are available in all Scandinavian countries, and in 2001 the consumption of benzodiazepines (in DDD/1000 inhabitants/ day) was 14.9 in Denmark, 21.5 in Finland, 20.8 in Iceland, 13.1 in Norway, and 11.7 in Sweden.63 Respectively, the consumption of cyclopyrrolones was 17.7 in Denmark, 29.5 in Finland, 34.5 in Iceland, 20.9 in Norway, and 24.3 in Sweden.63

CIRCADIAN RHYTHMS AND THEIR DISORDERS Morningness/eveningness or “chronotype” is dependent on genetic, environmental, and age-related factors. Using

the Munich ChronoType Questionnaire in more than 55,000 persons, it has been found that the most frequent (about 15%) type has midsleep on free days at 4:14 am and about 35% earlier and 50% later.79 (Midsleep is the halfway point between sleep onset and sleep end.) Women reach their maximum in lateness at around 19.5 years and men at 21 years, and this sex difference disappears around the age of 50; and people older than 60 years of age, on average, become even earlier chronotypes than they were as children.79 In a Finnish population, morning type increased from 16% among 25- to 29-year olds to about 50% among those 65 years and older.80 Respectively, evening type was observed in 11% to 12% among 25- to 29-year olds and the minimum (6%-7%) was found among 55- to 59-year olds. The estimate for overall genetic effect was 49.7%.80 Studies on the prevalences of circadian rhythm sleep disorders are scarce. Delayed sleep phase syndrome has been found in 0.17% among Norwegians aged 18 to 67 years81 and in 0.13% among Japanese aged 15 to 54 years,82 and the number of cases seems to have increased in the past few decades,83 being about 1.66% in Japanese university students.84 In Europeans aged 15 to 18 years a circadian rhythm disorder was found in fewer than 0.5%.85 One study has suggested that the prevalence of shift-work sleep disorder is about 10%.86

EXCESSIVE SLEEPINESS AND HYPERSOMNIA The feeling of not being alert is common, occurring both as a physiologic everyday phenomenon and as a symptom of sleep disorders.1,2 In spoken language, this feeling is probably most often called sleepiness but the actual meaning varies. By definition, sleepiness implies an increased risk of falling asleep,2 but the complaint of sleepiness is sometimes used to describe physical tiredness, fatigue, and loss of mental alertness without an increase in sleep behavior— conditions often associated with a decreased ability to fall asleep, contrary to true sleepiness. Abnormal sleepiness is often called excessive daytime sleepiness (EDS), but also this condition is difficult to be defined, because falling easily asleep or inability to stay awake may be normal and a desired everyday phenomenon (e.g., in the evening when going to bed). EDS has also been labeled as a disease or a disorder, although it is a symptom of a sleep disorder or of another disease. Our own studies exemplify these problems.87 Among those reporting daytime sleepiness every or almost every day, 19.5% of women and 42.3% of men were frequent snorers (snoring on at least 3 nights per week), 25% had scores suggesting moderate to severe depression, 25% had insomnia at least every other day, 10% were regular hypnotic or tranquilizer users, and 10% reported insufficient sleep. Thus, a “tired” or “sleepy” (in the patient’s words) person may have insomnia and not EDS or hypersomnia. In practice, it must be remembered that descriptions of the symptoms are related to the person’s feelings, emotions, level of education, and cultural background. Sleep researchers usually talk about sleepiness when referring to poor vigilance, lack of alertness, and tendency to fall asleep, but traffic researchers often use the terms, fatigue



CHAPTER 61  •  Epidemiology of Sleep Disorders  699

Table 61-3  Occurrence of Excessive Sleepiness REFERENCE (COUNTRY)

NO. SUBJECTS; AGE RANGE (YR)

DEFINITION OF SLEEPINESS (WORDING OF QUESTIONS)

METHODS

OCCURRENCE (%)

Excessive Sleep Time Karacan et al.99 1976 (USA)

1645; 18-70

Too much sleep

Questionnaire

0.3

Bixler et al.74 1979 (USA)

1006; 18-80

Sleeping too much

Questionnaire

Current: 4.2 (past 7.1) 18-30 yr: 9.9 31-50 yr: 2.3 51-80 yr: 1.8

Ford and Kamerow67 1989 (USA)

7954; 18-65

Ever a period of 2 wk or longer sleeping too much

Direct structured interview using diagnostic interview schedule

2.8 (m), 3.5 (f) 18-25 yr: 5.8 26-44 yr: 3.7 45-64 yr: 1.5 65+ yr: 1.6

Breslau et al.100 1996 (USA)

1007; 21-30

Definition and methods as in Ford and Kamerow67 (1989)

14.7 (m), 17.3 (f)

Ohayon et al.101 1997 (Great Britain)

4972; 15-100

Getting too much sleep

Telephone interview

3.2

Roberts et al.92 1999 (USA)

2730; 46-102

Sleeping too much nearly every day in the last 2 weeks

Questionnaire

6.0 and 1 year later 7.2, 7.4 (m) and 7.2 (f) 50-59-yr: 6.0 and 1 year later 7.1 60-69 yr: 5.5 and 5.2 70-79 yr: 8.4 and 10.3 80+ yr: 9.4 and 6.3

Saarenpää-Heikkilä et al.64 1995 (Finland)

574; 7-17

Sleeping in lessons often or always

Questionnaire (both subject and parents)

3 (m), 0 (f)

Partinen and Rimpelä66 1982 (Finland)

2016; 15-64

Involuntary sleep attacks daily or almost daily

Telephone interview

3.4 (m), 2.5 (f)

Kaneita et al.95 2005 (Japan)

28,714; 20-70+

Fall asleep when must not sleep

Questionnaire (e.g., when driving)

2.8 (m), 2.2 (f) 20-29 yr: 4.6 (m), 4.0 (f) 30-39 yr: 3.8 (m), 2.8 (f) 40-49 yr: 3.5 (m), 3.0 (f) 50-59 yr: 2.1 (m), 1.9 (f) 60-69 yr: 1.8 (m), 0.9 (f) 70+ yr: 0.9 (m), 0.7 (f)

Hays et al.96 1996 (USA)

3962; 65-85

Most of the time sleepiness, forcing to take a nap

Interview

25.2

Ganguli et al.35 1996 (USA)

1050; 66-97

Ever becoming uncontrollably sleepy so cannot help falling asleep

Interview

18.9 (no gender difference)

Saarenpää-Heikkilä et al.64 1995 (Finland)

574; 7-17

Sleepiness always or often

Questionnaire (both subject and parents)

20 (m), 22 (f)

Gaina et al.98 2007 (Japan)

9261; 12-13

Sleepiness

Questionnaire

Almost always: 20.7 (m), 29,6 (f) Often: 44.6 (m), 50.4 (f)

Chung and Cheung102 2008 (Hong Kong Chinese)

1629; 12-19

ESS >10

Questionnaire

41.9 (m < f)

Ohida et al.97 2004 (Japan)

106,297; 13-18

Excessively sleepy during the daytime always

Questionnaire

13-yr: 14-yr: 15-yr: 16-yr: 17-yr: 18-yr:

Sleep Attacks

Daytime Sleepiness

6.0 (m), 9.2 (f) 8.3 (m), 10.5 (f) 10.6 (m), 12.3 (f) 13.8 (m), 16.6 (f) 13.9 (m), 15.3 (f) 14.9 (m), 15.5 (f) Continued

700  PART II / Section 8  •  Impact, Presentation, and Diagnosis Table 61-3  Occurrence of Excessive Sleepiness—cont’d DEFINITION OF SLEEPINESS (WORDING OF QUESTIONS)

METHODS

OCCURRENCE (%)

3871; 15-18

ESS >10

Questionnaire

14.9 (m), 18.2 (f)

Ohayon et al.101 1997 (Great Britain)

4952; 15-100

Feeling greatly sleepy daily for at least 1 month

Telephone interview using Sleep-EVAL expert system

4.4 (m), 6.6 (f)

Souza et al.104 2002 (Brazil)

408; 18-60+

ESS >10

Interview

18.9 18-29 yr: 19.3 30-39 yr: 17.9 40-49 yr: 15.1 50-59 yr: 26.3 60+ yr: 19.6

Hara et al.105 2004 (Brazil)

1066; 18-60+

Sleepiness during the previous month ≥3 times per week

Interview

16.8 18-29 yr: 30.7 30-44 yr: 29.6 45-59 yr: 25.7 60+ yr: 14.0

Hublin et al.87 1996 (Finland)

11,354; 33-60

Sleepiness daily or almost daily

Questionnaire

6.7 (m), 11.0 (f)

Joo et al.106 2008 (Korea)

4405; 40-69

ESS >10

Questionnaire

10.7 (m), 13.7 (f) 40-49 yr: 10.2 (m), 11.2 (f) 50-59 yr: 13.1 (m), 20.5 (f) 60+ yr: 8.8 (m), 13.3 (f)

Tsuno et al.107 2007 (France)

2259; 65-96

ESS >10

Questionnaire and clinical evaluation

12.0 (m), 6.0 (f)

REFERENCE (COUNTRY) Joo et al. (Korea)

103

2005

NO. SUBJECTS; AGE RANGE (YR)

ESS, Epworth Sleepiness Scale; f, female; m, male.

or drowsiness.88 Sleeping alleviates sleepiness at least temporarily whereas resting without sleep does not. Fatigue, on the contrary, may be alleviated by having a pause, resting, physical exercise, and management of stress. Chronic fatigue is usually multifactorial in etiology, and it is generally not relieved by usual restorative techniques.88 Fatigue (57%), tiredness (61%), and lack of energy (62%) may be more frequent complaints than sleepiness (47%) in patients with sleep apnea.89 Also in primary care, complaints of chronic fatigue may be more common (20%-25%) than complaints of excessive sleepiness (5%-15%).90,91 Table 61-3 provides a summary of studies on daytime sleepiness.35,64,66,67,74,87,92,95-107 Depending on the wording, there is approximately a 100-fold difference in occurrence, ranging from 0.3% to more than 30%, and in most of the studies the range is from 5% to 15%. The prevalences of excessive sleep time or hypersomnia-like states are mostly around 5% in adults (no studies on children), with no clear gender difference. The prevalence may be age dependent, although the results are conflicting (decreases67,74 or increases92,93). In the classic study by Ford and Kamerow,67 64% of hypersomniacs had a psychiatric disorder in two interviews with a 1-year interval, most commonly an anxiety disorder or major depression. Similar findings are

reported from many European countries.94 Studies with two assessments of excessive sleep have shown stability of the symptom in less than one third.92 Sleep attacks (involuntary sleep episodes during awake periods) also mostly seem to occur in a few percent of the population in all age-groups, with no clear difference between the sexes and with conflicting results as to age-dependence (decreases95 or increases35,96 with age). Frequent or excessive (subjective) daytime sleepiness occurs in 10% to 15%. It occurs more often in school-aged children (with large differences between studies in the same country97,98) or young adults than in middle-aged or older adults. In most studies, sleepiness is more prevalent among women than among men. The variability of the results in different studies can be explained by differences in the definition of sleepiness and by other methodological aspects. Comparison of the results is difficult, but real differences in different populations probably exist. One problem is how “excessive” is understood in different studies. In questionnaires, the word “excessive” is subjective, and it should be compared with something that the responder considers normal for him or her. There are no studies on the population prevalences of recurrent hypersomnia or idiopathic hypersomnia.



CHAPTER 61  •  Epidemiology of Sleep Disorders  701

Table 61-4  Prevalence Studies on Narcolepsy-Cataplexy REFERENCE (COUNTRY)

FREQUENCY (PER 100,000)

95% CI*

BASE POPULATION (AGE RANGE, YR)

METHODS

Dement et al.123 1972 (USA)

50†

NA

NA (?) Bay area

Population sample Newspaper ad, telephone interview

Dement et al.124 1973 (USA)

67‡

NA

NA (?)

Population sample TV ad, telephone interview

9-230

12,469 (12-16)

Population sample Questionnaire, personal interview Personal interview

Honda109 1979, Honda et al.110 1983 (Japan)

160

Hublin et al.114 1994 (Finland)

26

0-56

11,354 (33-60) (Finnish twin cohort)

Population sample Questionnaire Ullanlinna Narcolepsy Scale Telephone interview Polygraphy HLA typing

Ohayon et al.118 1996 (UK)

40

0-96

4972 (15-100)

Population sample Telephone interview; Sleep-EVAL questionnaire

Silber et al.119 2002 (USA)

36

NC

97,667 (0-109) Olmsted County, Minnesota

Review of medical records covering 1960-1989

Wing et al.115 2002 (Hong Kong)

34

10-117

9851 (18-65)

Population sample (Chinese) as in Hublin et al.114 (1994)

Ohayon et al.94 2002 (five European countries)

47

NA

18,980 (15-100)

Population sample Telephone interview; Sleep-EVAL questionnaire

Shin et al.116 2008 (South Korea)

15

0-31

20,407 (14-19)

High school students as in Hublin et al.114 (1994)

Longstreth et al.120 2008 (USA)

22

19-25

1,366,417 (18 or more)

Physician-made diagnosis in one county covering 2001-2005

Heier et al.117 2009 (Norway)

22

6-80

8992 (20-60)

Population sample as in Hublin et al.114 (1994)

NA, not applicable; HLA, human leukocyte antigen. *95% confidence interval (CI) for the frequency of narcolepsy per 100,000 of population. † Estimated from San Francisco Bay area population (4 million), newspaper circulation (1.2 million), number of respondents (196) and interview-confirmed narcolepsy cases (114), and number of persons seeing/not seeing and responding/not responding to a control advertisement. ‡ Estimated from number of television homes in Los Angeles area (2,290,200), rating of number of viewers of the advertisement (56,576), number of respondents (165), and interview-confirmed narcolepsy cases (35); 30% sampling error and errors in making the diagnosis.

NARCOLEPSY AND NARCOLEPSY-LIKE SYMPTOMS There are about 30 studies published on the prevalence on narcolepsy (most of them on narcolepsy-cataplexy) with considerable differences in the figures. Highest prevalences (up to 30%) are based on questionnaire data without follow-up testing, and the next highest (0.2%-0.8%) on studies with self-reported diagnosis.108 In most studies with more intensive screening or clinical evaluation of suspected narcoleptics the prevalence of narcolepsy-cataplexy falls between 0.025% and 0.05%, or 25 to 50 per 100,000 population, and the 95% confidence intervals (CIs) for the frequencies overlap in the majority of them (Table 61-4). There are some exceptions. The highest figures are from Japan109,110 based on interviews of symptomatic schoolaged children selected by questionnaire, giving “a suspect

of narcolepsy” in 160 per 100,000 and a surprisingly high prevalence (7.6%) of “interview-confirmed cataplectic attacks,” which suggests criteria different from other studies. The lowest frequency (0.23 per 100,000) is found among Israeli Jews,111 but this was based on an extrapolation of sleep clinic samples to the entire population. However, narcolepsy is likely hugely underdiagnosed.111a The prevalence of narcolepsy-cataplexy seems to be consistent despite considerable differences methods, ethnic groups, and population frequencies of DQB1*0602, and so on between the studies.112 For example, there are three studies using a simple screening method called the Ullanlinna Narcolepsy Scale (UNS) developed and validated for population studies.113 It consists of 11 items assessing cataplexy-like symptoms and the tendency to fall asleep. Using the UNS, telephone interviews, and polygraphic confirmation of the diagnosis, the prevalence of narcolepsy

702  PART II / Section 8  •  Impact, Presentation, and Diagnosis

with clinically significant cataplexy has been found to be of same order among adult Finns (26 per 100,000),114 adult Chinese in Hong Kong (34 per 100,000),115 Korean adolescents (15 per 100,000),116 and adult Norwegians (22 per 100,000).117 Similar prevalences have been obtained in Europeans using telephone interviews (Sleep-EVAL questionnaire) without any other examinations (40 or 47 per 100,000)94,118 and in the United States using a review of medical records (36 per 100,000)119 and physician-made diagnoses (22 per 100,000).120 There are only a couple of studies on narcolepsy without cataplexy, giving a prevalence of 20 per 100,000 in adults in the United States119 and 34 per 100,000 in Korean adolescents,116 which may be gross underestimations.112 However, it can be difficult to assess the true prevalence because diagnostic Multiple Sleep Latency Test criteria may be 100 times more prevalent in a population than narcolepsy.121 One study gives an incidence rate of 1.37 (0.74 for narcolepsy with cataplexy) per 100,000 persons per year. Some studies suggest that narcolepsy may be slightly more common in men.108 Analytic epidemiologic studies have found associations between narcolepsy and body mass index (BMI), immune responses, and stressful life events, but these may rather reflect consequences than cause of disease.108 Although typical cataplexy is pathognomonic of narcolepsy, mild forms are difficult to separate from similar physiologic phenomena. As mentioned, reports of EDS in the population are common. In Finland, 29.3% of the people reported (at least once during his or her lifetime) feelings of limb weakness associated with emotions.114 If this is considered as evidence of cataplexy and combined with the occurrence of daytime sleep episodes at least 3 days per week, 6.5% of the population would have fulfilled the minimal diagnostic criteria for narcolepsy of the International Classification of Sleep Disorders.114,122 Therefore, using only questionnaires in population studies may increase the risk of too high prevalence rates.

SNORING, SLEEP-DISORDERED BREATHING, AND SLEEP APNEA SYNDROME Habitual snoring is defined as snoring almost every night or every night or as snoring at least 5 nights per week. It is almost always present in patients with obstructive sleep apnea syndrome (OSAS). In the first large-scale epidemiologic study on snoring, about 24% of San Marino men and 14% of San Marino women were reported to habitually snore (Table 61-5125-137). In Finland, 9% of adult men and 3.6% of adult women snore always or almost always when asleep.125 A Syndrome or a Disease? Obstructive sleep apnea syndrome is a public health disease. It is the most common organic sleep disorder causing excessive daytime somnolence. Sleep-related breathing disorders (SRBD) and sleep-disordered breathing (SDB) refer to the same clinical disorder. In this chapter, we still use the term OSAS, although hypopneas are now included in the syndrome.

According to various cross-sectional studies, the lowest rates for the prevalence of OSAS among adult men are 1% to 4%. There is an age relationship, so the prevalence of OSAS among men 40 to 59 years old may be greater than 4% or 8%.133 OSAS is less common is younger and older age groups. After menopause, up to the age of 65, OSAS is almost as common among women as among men. Obstructive sleep apneas are part of the complex of heavy snorer’s disease as defined by Lugaresi and colleagues.138 Heavy snoring (i.e., partial upper airway obstruction), even without apneas, is associated with higher pulmonary arterial pressure, daytime sleepiness, arterial hypertension, and insulin resistance.139-143 Heavy snoring is also associated with case-fatality and short-term mortality after a first acute myocardial infarction.144 Visceral central body obesity, measured by waist circumference, is strongly related to SBD.145 Among morbidly obese patients the proper diagnosis may be morbid obesity with obstructive sleep apnea.146 Another example is acromegaly with symptomatic sleep apnea. This is analogous to a patient with a brain tumor who has symptomatic epilepsy. The primary diagnosis is brain tumor (e.g., glioma), and epilepsy is a secondary symptom caused by the brain tumor. The severity of sleep apnea must be properly quantified, not only by indices (e.g., apnea index [AI], apnea-hypopnea index [AHI], or respiratory disturbance index [RDI]) but also by the number of oxygen desaturations, presence of cardiovascular effects, and degree of daytime sleepiness. Snoring and sleep apnea are more common in the supine sleeping position than in the lateral positions. It is therefore necessary to give indices separately for supine and lateral sleeping positions. In clinical studies, sequential apnea indices should always be compared relative to sleeping position. The diagnostic criteria should also be adjusted for age. Bixler and associates147 studied 20- to 100-year-old men. The criteria for OSAS were an AHI of at least 10 in the sleep laboratory and fulfillment of clinical criteria, including the presence of daytime symptoms. OSAS was found in 3.3% of the sample, with its maximum among 45- to 64-year-old men. Although the prevalence of sleep apnea increases with age the clinical impact of apnea seems to decrease among elderly people.148-150 Prevalence of Sleep Apnea The first large epidemiologic polysomnographic study was conducted in Madison, Wisconsin.133 The authors estimated that 2% of women and 4% of men in the middleaged work force met the minimal diagnostic criteria for the sleep apnea syndrome, defined as an AHI of 5 and daytime hypersomnolence.133 Up to 9% of women and 24% of men had an AHI of 5 without daytime somnolence. On examination of the subgroup of patients between the ages of 50 and 60, 4% of women and 9.1% of men were found to have an AHI exceeding 15.133 In a large U.S. population– based study,140,147 clinically defined sleep apnea (AHI ≥ 10 and daytime symptoms) occurred in 3.9% of men and 1.2% of women. The peak prevalence, 4.7% (95% CI, 3.1% to 7.1%), was found among men aged 45 to 64 years. Among the 20- to 44-year olds and those older than 65



CHAPTER 61  •  Epidemiology of Sleep Disorders  703

Table 61-5  Occurrence of Habitual Snoring

REFERENCE (POPULATION)

METHODS

1980 Lugaresi et al. (San Marino general population)

Interview

Partinen127 1982 (Army recruits)

DEFINITION/ WORDING OF HABITUAL SNORING

SEX

NO. SUBJECTS

AGE RANGE (YR)

PREVALENCE (%)

“Every night” (alternatives: no, sometimes, every

m

2858

3-94

24.1

f

2855

3-94

13.8

Questionnaire, clinical studies

Snoring always or almost always Snoring often or always

m

2537

18-29

Koskenvuo et al.125 1985 (Finnish population sample)

Postal questionnaire

“Snoring always or almost always”

m

3847

40-69

9

f

3864

40-69

3.6

Norton and Dunn 1985 (Canadian population sample)

Questionnaire filled during a medical visit

Snoring every night (reported by spouses)

m

1411 1211

3rd to 8th decade

13.2

f

Billiard et al.129 1987 (French army draftees)

Questionnaire completed under supervision

Snoring habitually

m

58,162

17-22

13.6

Gislason et al.130 1987 (Swedish men)

Postal questionnaire

“Loud and disturbing snoring” very often

m

4064

30-69

15.5

Cirignotta et al.131 1989 (Italian adults)

Postal questionnaire

Snoring always (alternatives: never, rarely,

m

1170

30-69

10.1

890

40-69

11.5

304

50-59

15.5

18 or older

10.2

126

128

2.9 9.5

5.6

Schmidt-Nowara et al.132 1990 (HispanicAmerican adults)

Interview using a questionnaire

“Regular and loud snoring” always (every night)

m

482

f

724

Young et al.133 1993 (state employees in Wisconsin)

Postal questionnaire (first stage of

Almost every night or every night snoring

m

1670

30-60

35

f

1843

30-60

28

Ali et al.134 1993 (English children)

Questionnaire filled by

“Snoring on most nights”

m, f

4-5

12.1

Jennum and Sjol135 1994 (Danish population sample)

Interview and clinical examinations

Snoring nightly (every night)

m

Total

30-60

19.1

f

1504

30-60

7.9

Kayukawa et al. (Japan, new outpatients)

Questionnaire, outpatient clinic visit

Habitual snoring

m

6445

Adults

16.0

Kaditis et al.136 2004 (Greek children and adolescents)

Questionnaire filled out by parents

Habitual snoring (snoring every night)

m, f

3680

1-18

1-6 yr: 5.3 7-12 yr: 4.0 13-18 yr: 3.8

Kuehni et al.137 2008 (English preschool children)

Population survey

Habitual snoring

m, f

6811

1-4

1 yr: 6.6 4 yr: 13.0

162

2000

782

5.4

f

years, the prevalence rate was 1.7%. Among women, the average prevalence was 1.2.140,147 In women, the prevalence of SDB increases after menopause; hormone replacement therapy is associated with lower occurrence of SDB.140,161 In the study by Bixler and coworkers.140 the prevalence of clinically defined sleep apnea among premenopausal women was 0.6%. Among postmenopausal women on hormone replacement therapy the prevalence was about the same (0.5%).140

6.5

The prevalence depends on the base population. OSAS is most frequent in persons 40 to 65 years old. One can safely estimate that the prevalence rate of OSAS in that age group is around 4% (3% to 8%) in men and 2% in women and that the absolute minimum prevalence of clinically significant OSAS is 1%. Among obese subjects, hypertensive persons, patients with adult-onset diabetes, and many patient groups with abnormal facial anatomy, the prevalence rates are significantly higher.

704  PART II / Section 8  •  Impact, Presentation, and Diagnosis Table 61-6  Occurrence of Obstructive Sleep Apnea Syndrome REFERENCE (COUNTRY)

METHODS

NO. SUBJECTS

AGE RANGE (YR)

CRITERIA

PREVALENCE (%)

Lavie151 1983 (Israel)

Questionnaire for industrial workers of whom 78 subjects had PSG

1262 (m)

18-67

AI ≥ 10, symptomatic

3.5 (1.0-5.9)

Telakivi et al.152 1987 (Finland)

Questionnaire. PSG recordings and clinical examination for potential subjects

1939 (m)

30-69

Snoring, EDS, and RDI > 10

0.4-1.4

Gislason et al.153 1988 (Sweden)

Questionnaire. PSG recordings and clinical examination for potential subjects

3201 (m)

30-69

Snoring, EDS, and AHI > 10

0.7-1.9

Cirignotta et al.131 1989 (Italy)

Questionnaire, telephone survey. PSG recordings and clinical examination for potential subjects Ambulatory oximetry recordings at home

1170 (m)

30-39

AI > 10, symptomatic

0.2-1.0

40-59

AI > 10, symptomatic

3.4-5.0

60-69

AI > 10, symptomatic

0.5-1.1

35-65

ODI4 > 20, symptomatic

0.3

ODI4 > 10

1.0

Stradling and Crosby154 1991 (Great Britain)

893 (m)

Young et al.133 1993 (Wisconsin, USA)

A sample of state employees. PSG recordings and clinical

352 (m)

30-60

250 (f)

30-60

Olson et al.155 1995 (Australia)

Questionnaire and home sleep recordings

1233 (m)

35-69

Bixler et al.147 1998 (USA)

Telephone survey. Random sample of men aged 20-100 yr A sleep laboratory study (PSG) for a subsample of men

4364 (m) Subsample: 741

20-100

Marin et al.156 1997 (Spain)

Personal interview, clinical examination, home oximetry A population sample

597 (m)

>18

Bixler et al.140 2001 (USA)

Telephone survey Random sample of women

12,219 (f)

A sleep laboratory study (PSG) for a subsample of women

Subsample: 1000

Male office workers

784 (m)

Ip et al.157 2001 (Hong Kong, China) Ip et al.158 2004 (Hong Kong, China)

969 (f)

625 (f) 20-100

30-60

Questionnaire and PSG in 153 Community samples of women

854 (f)

30-60

Questionnaire and PSG in 106

ODI4 > 5

4.6

Hypersomnia and RDI ≥ 5

4.0 (m) 2.0 (f)

AHI ≥ 15

4-18

AHI ≥ 10

7-35

AHI ≥ 5

14-69

AHI > 10 and clinical criteria fulfilled with daytime symptoms

All: 3.3 45-64 yr: 47

Loud snoring + EDS + abnormal home oximetry

2.2 (m)

AHI > 10 and clinical criteria fulfilled with presence of daytime symptoms

All (f): 1.2

0.8 (f)

Premenopause: 0.6 Postmenopause without HRT: 2.7 With HRT: 0.5

AHI ≥ 5 + EDS

4.1

AHI ≥ 15 + EDS

3.1

AHI ≥ 5 + EDS

2.1

AHI ≥ 15 + EDS

0.8

Kim et al.159 2004 (South Korea)

Examination of 5020 Korean subjects A subsample of 457 had PSG

5020

40-69

AHI ≥ 5 + EDS

4.5 (m); 3.2 (f)

Reddy et al.160 2009 (New Delhi, India)

Random community sample Questionnaire and PSG in 360

2505

≥ 18

AHI ≥ 5 + EDS

4 (m); 1.5 (f)

AHI, apnea–hypopnea index; AI, apnea index; EDS, excessive daytime sleepiness; f, female; HRT, hormone replacement therapy; m, male; NA, not applicable; ODI4, oxygen desaturation index (≥4% desaturation); OSAS, obstructive sleep apnea syndrome; PSG, polysomnography; RDI, respiratory disturbance index.



Role of Obesity as a Risk Factor for Snoring and Sleep Apnea Obesity is the most important risk factor for snoring and sleep apnea. The association is found without exceptions, which does not, naturally, mean that lean people could not have OSAS. Neck size162 and especially waist circumference145,163 are related to severity of sleep apnea and may be better indicators than BMI. Other Risk Factors for Snoring and Sleep Apnea Alcohol increases upper airway resistance and tends to induce obstructive sleep apnea in healthy people and especially among chronic snorers. In Great Britain, one drink per day increased the odds of mild or worse SDB by 25% (OR = 1.25; 95% CI, 1.07-1.46) among men. Among women, minimal to moderate alcohol consumption was not significantly associated with increased risk of SDB.164 Other risk factors include large adenoids or tonsils, rhinitis, and other abnormalities in the upper airways, such as those found in different syndromes of dysmorphia and in the mentally disabled. Also, smoking,165 acromegaly,166,167 and amyloidosis168 are known risk factors for SDB. Organic solvent use was associated with increased prevalence of SDB in Sweden169 but not in Germany.170 Snoring and Sleep Apnea in Children Habitual snoring and sleep apnea during childhood (see Tables 61-5 and 61-6125-137,140,147,151-160) may be associated with significant harmful effects on health. Childhood obesity and adenotonsillar hypertrophy are among the most common associated factors.171 In an Italian study, 118 (7.3%) of 1615 children 6 to 13 years of age were often snorers.172 Children with rhinitis were more than twice as likely to be habitual snorers than others. A positive correlation between parental smoking and snoring in children exists. In Singapore, 6% of children snore habitually.173 In Iceland,174 the minimal prevalence of obstructive sleep apnea among children 6 months to 6 years old was 3.2%. In another study, significant sleep and breathing disorders occurred in 0.7% of 4- to 5-year olds.134 The prevalence of SBD among adolescents aged 12 to 16 years was similar to that reported for younger children. In Greece, a survey of 3680 people aged 1 to 18 years revealed a prevalence of habitual (every night) snoring of 5.3%, 4%, and 3.8% among 1- to 6-, 7- to 12-, and 13- to 18-year-old subjects, respectively.136 Sleepiness at school was more common in habitual snorers than in nonhabitual snorers (4.6 vs. 2%, P = .03). Based on 70 random polysomnographic recordings among the 307 snorers without adenoidectomy and/or tonsillectomy the estimated prevalence of OSAS was 4.3%. In a population survey of 6811 children aged 1 to 4 years in the United Kingdom (from parent’s reports) the prevalence of habitual snoring was 7.9%, and 0.9% of children were reported to have habitual snoring and sleep disturbance. Habitual snoring increased with age from 6.6% in 1-year olds to 13.0% in 4-year olds. Habitual snoring was associated with parent’s smoking, road traffic, single parenthood, white but not South Asian children, and socioeconomic deprivation.137 Atopy and respiratory infections were strongly associated

CHAPTER 61  •  Epidemiology of Sleep Disorders  705

with snoring, but BMI was not,137 which shows that the association between childhood obesity and SBD is not simple.175 Sleep Apnea among Elderly People The prevalence of habitual snoring seems to decrease after the age of 65 or 70 years (see Table 61-5). According to Ancoli-Israel and colleagues,176 62% of elderly people have an RDI of at least 10. Bixler has emphasized the need to adjust the criteria for OSAS in elderly persons.147 A cohort of 198 noninstitutionalized elderly individuals (mean age at entry, 66 years) were followed up to 12 years.148 The mortality ratio for sleep apnea, defined as an RDI greater than 10, was 2.7 (95% CI, 0.95 to 7.47). In a cohort of 426 elderly people those with an RDI of 30 had significantly shorter survival. RDI was not an independent predictor of death among the elderly during 5 years follow-up after adjustment for age, cardiovascular disease, and pulmonary disease.149 The clinical significance of sleep apnea among elderly people remains open. Arterial Hypertension and Snoring An association between always or almost-always snoring and arterial hypertension exists. Among 41- to 60-year-old people in San Marino,126 hypertension was present in 15.2% of habitual snorers and in 7.5% of nonsnorers. In a cross-sectional study in Finland the odds of arterial hypertension were increased by 94% (OR 1.94) among habitual male snorers versus nonsnorers after adjustment for BMI and age.177 Case-control studies have shown that the prevalence of sleep apnea among patients with essential hypertension is around 30%. In another study,178 38% of the hypertensive subjects and 4% of normotensive subjects had an AHI of higher than 5.178 In middle-aged adults with drug-resistant hypertension the prevalence of OSA may be over 80%.179 There are now several studies, including prospective studies, showing that SDB in the form of habitual snoring or sleep apnea is a determinant of risk of arterial hypertension but occasional snoring is not associated with an increased risk.180-184 Snoring, Sleep Apnea, and Heart Disease An association of habitual snoring with electrocardiographic changes and arrhythmias has been reported.185 The association of snoring and ischemic heart disease was tested in a population consisting of 3847 men and 3664 women 40 to 69 years old. Reported angina pectoris was associated with habitual snoring among men (risk ratio, 1.9) but not among women (risk ratio, 1.2). The association was also found after adjustment for arterial hypertension and BMI.177 These results were confirmed in a prospective follow-up study of 4388 men 40 to 69 years old. The age-adjusted risk ratio of ischemic heart disease between often or always snorers and nonsnorers was 1.91 (1.18-3.09). An additional adjustment for BMI, history of arterial hypertension, smoking, and alcohol use decreased the risk ratio to 1.71 (0.96-3.05).186 In a casecontrol study with 50 patients with myocardial infarction and 100 control subjects, snoring every night was associated with myocardial infarction. The odds ratio was 2.35 (1.18-4.67) when patients were compared with both hospital control and population control subjects. Adjustment

706  PART II / Section 8  •  Impact, Presentation, and Diagnosis

by smoking, arterial hypertension, diabetes mellitus, and alcohol consumption did not change results.187 In Australia, men with an AI of more than 5.3 had a 23.3-fold (95% CI, 3.9 to 139.9) risk of myocardial infarction than men with an AI of less than 0.4. The mean AI was 6.9 in patients with myocardial infarction versus 1.4 in the control subjects.188 The association was independent of age, BMI, arterial hypertension, smoking, and cholesterol level. Fifty patients 61 ± 6 years old with coronary artery disease were investigated prospectively. In 25 patients (50%), the AI was more than 10/hour sleep. EDS was exhibited by 8 of the 25 patients.189 Several cross-sectional and prospective studies have now confirmed that there is an association between habitual snoring, sleep apnea, and ischemic heart disease142,144,190-193 or congestive heart failure.194,195 The minimum prevalence of OSAS among patients with coronary disease can be estimated as about 16%. Snoring, Sleep Apnea, and Brain Infarction An association between cerebral infarction and habitual snoring has been found in many studies.196 In a casecontrol study of 50 male patients with brain infarction and 100 male control subjects,197 the risk ratio of brain infarction between habitual or often snorers and occasional or never snorers was 2.8. Between habitual snorers and occasional or never snorers, the risk ratio of stroke was 10.3. After adjustments for several confounding variables among 177 male patients and control subjects matched for age and sex, the independent odds ratio relating to snoring and stroke remained at 2.13.198 Other studies have provided supporting results. In Italy,199 the adjusted (age, gender, obesity, diabetes, dyslipidemia, smoking, use of alcohol, and hypertension) odds ratio for “often or always snoring” in relation to ischemic brain infarction was 1.9 (1.2-2.9). Neau and associates200 studied 133 patients 45 to 75 years old and 133 control subjects matched for age and sex. The prevalence of habitual snoring was 23.3% among patients with stroke and 8.3% among their controls. The odds ratio for habitual snoring was 3.4 (1.5-7.6). The odds ratio for “often or always snoring” was 1.7 (1.03-2.93). After adjustment for age, sex, arterial hypertension, cardiac arrhythmia, and obesity, the odds ratio of habitual snoring for stroke remained statistically significant (2.9; 1.3-6.8). The risk of ischemic stroke seems to be especially high among habitually snoring men with arterial hypertension.200 A significant association between occurrence of sleep apnea and ischemic stroke exists.201-204 The causal relationships remain still somewhat open.196,205 Snoring and Sudden Death An autopsy was performed in 460 consecutive cases of sudden death among 35- to 76-year-old men. The closest cohabiting person to each deceased man was interviewed. The mean age was 55.4 years, and the mean BMI was 26.3 kg/m2. Among the obese snorers (N = 82), apneas had been observed “occasionally,” “often,” or “habitually” in 49 cases. Death was classified as cardiovascular in 186 cases (40.4%). The cardiovascular cause of death was more common among the habitual and often snorers than among

occasional or never snorers. Habitual snorers died more often while sleeping. Habitual snoring was found to be a risk (OR 4.07; 1.45-11.45) for cardiovascular early morning death between 4 and 8 am.206 In a follow-up study of 34 obese men, a history of obstructive sleep apnea was a strong risk factor for sudden cardiovascular death. On autopsy, the degree of atherosclerosis was moderate in all cases.207 Snoring and Dementia The occurrence of snoring was studied in 46 patients with Alzheimer’s disease, in 37 patients with multiinfarct dementia, and in a random sample of 124 elderly community residents.208 The demented patients snored twice as frequently as the control subjects. No difference in the occurrence of snoring was found between the two types of dementia. Among 235 nursing home residents 70% had an AHI of 5. The presence of sleep apnea correlated with results of dementia rating scales.209,210 Clinical reports exist about associations between sleep apnea and dementia,210,211 but larger epidemiologic studies are lacking. Evolution of Obstructive Sleep Apnea Syndrome Evolution of OSAS and the effects of treatment are handled in greater detail elsewhere in this textbook. OSAS may be a lethal disease if not treated. There are several studies showing an increased risk of cardiovascular complications and death in patients with at least moderate (AI > 20) or severe (AI > 40) OSAS.212-216 Mortality of mild sleep apnea, with AHI less than 15, does not seem to differ significantly from the mortality of the average population.216 The increased risk is found especially among middle-aged people with SDB, but not in the elderly, in whom several other risk factors for cardiovascular disease and death coexist with OSAS.216 In a Swedish study of 3100 men aged 30 to 69 followed for 10 years, 213 men died, 88 of cardiovascular diseases. In that study, those with isolated snoring or excessive daytime sleepiness (EDS) displayed no significantly increased mortality but the combination of snoring and EDS was associated with a significant increase in mortality. The relative rates decreased with increasing age as in other studies.217 Men younger than the age of 60 with both snoring and EDS had an age-adjusted total death rate that was 2.7 times higher than men with no snoring or EDS (95% CI 1.6 to 4.5). The corresponding age-adjusted hazard ratio for cardiovascular mortality was 2.9 (1.3-6.7) for subjects with both snoring and EDS. Further adjustment for BMI and reported hypertension, cardiac disease, and diabetes reduced the relative mortality risk associated with the combination of snoring and EDS to 2.2 (1.3-3.8) and the relative risk of cardiovascular mortality to 2.0 (0.8-4.7).217 Continuous positive airway pressure (CPAP) is an effective and life-saving treatment of severe OSAS.218-221 Studies show that CPAP is effective in short-term trials in the treatment of mild sleep apnea.222-224 A few prospective follow-up studies142,221,225,226 have been published, but more well-done prospective epidemiologic studies are still needed, especially based on intention to treat analysis. Different surgical methods (e.g., uvulopalatopharyngoplasty,



CHAPTER 61  •  Epidemiology of Sleep Disorders  707

Table 61-7  Prevalence of Restless Legs Syndrome REFERENCE (COUNTRY)

POPULATION; NO. SUBJECTS

METHODS, CRITERIA

PREVALENCE (%)

Ekbom230 1945 (Sweden)

Patients in a physician’s practice; N = 500

Presence of restless legs (original description)

5

Lavigne et al.233 1994 (Canada)

Population sample, age 18 yr+; N = 2019

Leg restlessness at bedtime, face-to-face interviews

10-15

Phillips et al.234 2000 (USA)

Kentucky random population of men and women, aged ≥ 18 yr, N = 1803

Telephone interview, presence of restless legs 5 or more times/month At least once per month

18-29 yr: 3 30-79 yr: 10 80+ yr: 19 All ages: 19.4

Rothdach et al.235 2000 and Berger et al.236 2002 (Germany)

German elderly population sample, age 65-83 years, N = 369

RLS-criteria and neurologic examination; IRLSSG criteria

Overall: 9.8 m: 6.1 f: 13.9 65-69 yr: 9.8 70-74 yr: 12.75 75+ yr: 7.4

Tan et al.237 2001 (Singapore)

General population sample, 155 subjects aged ≥ 55 yr and 1000 consecutive patients aged ≥ 21 yr in a health center

IRLSSG criteria

0.6 in the population; 0.1 among the patients

Ulfberg et al.238 2001 (Sweden)

A random sample of men in Sweden; N = 4000

IRLSSG criteria

5.8

Ulfberg et al.239 2001 (Sweden)

Random sample of women aged 18-64 yr in Sweden; N = 200

IRLSSG criteria

11.4

Ohayon and Roth240 2002 (5 European countries)

UK, Germany, Italy, Portugal, and Spain; N = 18,980; aged 15-100 yr

Telephone surveys, SleepEVAL questionnaire

RLS: 5.5 PLMD: 3.9 with ICSD criteria

Sevim et al.241 2003 (Turkey)

Turkish adults, N = 3234

IRLSSG criteria, face-to-face personal interviews

3.19

Bhowmik et al.242 2003 (India)

Case-control study. N = 121 hemodialysis patients and 99 control patients

Questionnaire with RLScriteria; ENMG

Patients on hemodialysis: 6.6 Control patients: 0.0

Nichols et al.243 2003 (USA)

A primary care patient population seen by family physicians, N = 2099

IRLSSG criteria, examined by family physicians

All 4 symptoms present: 24.0 Symptoms present at least weekly: 15.3

Suzuki et al.244 2003 (Japan)

Japanese pregnant women, N = 16,528

Questionnaire survey in 500 maternity services

19.9

Rijsman et al.245 2004 (The Netherlands)

Population of a health center in the Netherlands aged ≥ 50 yr; N = 1437

Questionnaire

7.1

Gigli et al.231 2004 (Italy)

N = 601 patients with endstage renal disease

IRLSSG criteria, questionnaire

21.5

Ulfberg, Nyström246 2004 (Sweden)

Blood donors, N = 946, aged 18-64 yr

IRLSSG criteria, questionnaire

f: 24.7 m: 14.7

Högl et al.247 2005 (Austria)

Population sample, aged 50-89 yr, N = 701

Interviews, clinical examination, laboratory

10.6

Allen et al.229 2005 (USA)

Population sample, aged > 18 yr, N = 15,391 (REST study)

IRLSSG criteria, questionnaire

RLS weekly: 5 RLS symptoms at least on 2 days per week: 2.7

Kim et al.248 2005 (South Korea)

Population sample, adults

IRLSSG criteria, questionnaire

f: 15.4 m: 8.5

Winkelman et al.249 2006 (USA)

Wisconsin Sleep Cohort, N = 2821

IRLSSG criteria, slightly modified, questionnaire

RLS at least weekly

Nomura et al.250 2008 (Japan)

N = 2812

Rural population telephone interview IRLSSG criteria, questionnaire

1.8

f: 14.2 m: 6.6

f: 11.2 m: 9.9 f: 2.3 m: 1.2

ICSD, International Classification of Sleep Disorders; IRLSSG, International Restless Legs Syndrome Study Group; PLMD, periodic limb movement disorder.

708  PART II / Section 8  •  Impact, Presentation, and Diagnosis Table 61-8  Population Prevalences of Parasomnias* Childhood

PARASOMNIA

OCCURRENCE (%) ALWAYS OR OFTEN/NOW AND THEN/EVER

Adulthood OCCURRENCE (%) ALWAYS OR OFTEN/NOW AND THEN/EVER

REFERENCES

REFERENCES

Sleep terrors

0.9-1.8/8.4/ 28-39.8

264, 271-273

–/–/<1.0-2.2

274, 275

Sleepwalking

0.9-2.8/ 5.7-14.2/14.5-21

264, 266, 271-273

0.1-0.6/0.9-3/2

74, 266, 274-276

Confusional arousals

–/–/17.3

2

–/–/4.2

275

Isolated sleep paralysis

–/–/–

–

–/–/6.2-40

85, 277-280

Nightmares

1-10.9/17.8-32.0/ 37.2-78

270, 271, 273, 281, 282

0.9-5.8/8-29/5.3-68.8

74, 260, 270, 276, 283

Sleep-related hallucinations

–/–/–

–

Hypnagogic: 2.52.9/17.2-21.7/19.7— almost all hypnopompic: 0.9/5.7/6.6

118, 276, 284

Sleeptalking

3.9-13.9/23-59.8/ 84.4

264, 273, 281, 285, 286

1.5-2.1/4.4/5.3-50.0

74, 276, 285

Sleep enuresis

3.6-5.8/6.7-13/ 3.1-26.5

264, 267, 273, 281, 287-289

0.3/0.1/0.07-5.0

267, 290, 291

Sleep bruxism

4.7-6.4/17.3/ 39.1-45.6

264, 268, 273, 292

1.0-8.2/4.2/7.5-27.2

276, 293-295

*The lowest and the highest frequency of the original works (references) are given. “Childhood” refers to studies in populations aged up to about 15 years.

radiofrequency tissue ablation) are used to treat snoring and sleep apnea, but there are only a few studies with acceptable epidemiologic methodology. Weight loss and lifestyle change are effective.227,228

RESTLESS LEGS SYNDROME The prevalence of clinically significant restless legs syndrome (RLS), or Ekbom’s syndrome, among adults is probably 2% to 3%,229 which is close to Ekbom’s original estimations of about 5.4%.230 In earlier studies, RLS seemed to be less common in Asian countries than in Western world. When the same survey methods have been used, the occurrence of RLS seems to be quite similar all over the world. RLS is common. In general, the prevalence varies between 5% and 15%. The prevalence is higher among elderly people. In some patient groups, such as patients with end-stage renal disease in Western countries, the prevalence may be higher than 20%.231 Also more than 20% of pregnant women suffer from restless legs232 (Table 61-7229-231,233-250). REM SLEEP BEHAVIOR DISORDER In the current International Sleep Classification,2 REM sleep behavior syndrome (RBD) is considered a parasomnia, but it could also be classified as a sleep-related movement

disorder. RBD is an important topic in sleep medicine and also in movement disorders research because it seems to be a premonitory sign of Parkinson’s disease and alphasynucleinopathies.251-254 In clinical follow-up studies, 30% or more of subjects with RBD develop Parkinson’s disease within 7 years. RBD is also associated with cognitive decline in Parkinson’s disease, and it is commonly present in patients with multisystem atrophy and Lewy-body dementia.255-259 At the moment we lack population-based studies about the prevalence of RBD.

PARASOMNIAS Table 61-8 summarizes the prevalences of 10 parasomnias, mainly based on population studies.* The figures given must be regarded only as crude ratings. Most of the studies are retrospective questionnaire studies, and recall bias may affect results.259a For example, regarding nightmares there can be up to 10 times higher frequencies when using short follow-up (1 month vs. 1 year) and a log instead of a questionnaire.260,261 There is also an obvious risk that the parasomnias occur without being noticed. Unless a cohabiting person reports the occurrence the subject may be unaware of the symptoms of *See references 2, 74, 85, 118, 260, 264, 266-268, and 271-295.



CHAPTER 61  •  Epidemiology of Sleep Disorders  709

sleeptalking or bruxism because of being asleep himself/ herself or of sleepwalking or sleep terror because of the impaired arousal and amnesia regarding the nocturnal episode. Moreover, because the frequency of parasomnias in children is strongly associated with age, it is difficult (or may even be misleading), for example, to give occurrence figures to sleep enuresis in “childhood.” Additionally, there are considerable methodological differences in the studies (e.g., definitions of specific parasomnias, questions asked also of parents). Co-occurrence of parasomnias is well-known, and the strongest associations are between sleeptalking, sleepwalking, nightmares, and sleep terrors.262-264 Parasomnias also run in families, and in genetic epidemiologic studies the proportions of total genetic variance in liability to certain parasomnias has been highest in childhood sleepwalking and enuresis (about two thirds)265-267 and 40% to 60% in childhood and adult sleeptalking, nightmares, and bruxism.265,268-270 The highest estimated proportions of shared genetic effects were between sleeptalking with sleepwalking (50%), with bruxism (30%), and with nightmares (26%).263 There are some association between parasomnias and psychopathology also based on population level. Serious psychiatric disorders (indicated by long-term antipsychotic medication and/or psychiatric hospitalization) are significantly associated with both childhood (OR ≤ 3.7) and adulthood (OR ≤ 5.9) nightmares occurring frequently, although this was the case only in the minority of the subjects (11.5% in childhood and 15.6% in adulthood nightmares in the most frequent categories).270 In sleeptalking, a similar association was found only in frequent talkers.269

❖  Clinical Pearl Because sleep disorders are very common in each age group, clinicians should inquire about their symptoms whenever evaluating new patients. The following possible problems should be investigated: 1. In young children • Trouble getting to sleep • Symptoms of insufficient sleep • Parasomnias • Excessive daytime sleepiness • Symptoms related to possible sleep apnea 2. In young and middle-aged adults: • Symptoms of insomnia • Excessive daytime sleepiness • Symptoms of restless legs syndrome • Sleep apnea 3. In older people: • Symptoms of insomnia • Excessive daytime sleepiness Chronic insomnia and chronic insufficient and/or poor sleep is related to many somatic and psychiatric disorders. Sleep-related issues should be part of routine clinical work and of all epidemiologic studies that investigate relationships between different exposures and outcomes.

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