In addition to awake EEG changes, there are changes during sleep in the elderly (Box 51.1) [54, 55]. As early as 1945, Liberson [56] described paroxysmal bursts of sleeplike EEG lasting 1–10 s in the eyes-resting state in elderly subjects, and the incidence of these bursts increased with the age of the subject. Liberson [56] termed these episodes microsleeps. Transient bursts of anteriorly dominant rhythmic delta waves are often noted in elderly subjects in the early stage of sleep. Gibbs and Gibbs [57] used the term anterior bradyrhythmia for this finding. Katz and Horowitz [58] obtained sleep-onset frontal intermittent rhythmic delta activity in normal elderly subjects, which should be differentiated from that associated with a variety of neurologic disorders. These are highly stimulus-sensitive and disappear in deeper stages of sleep. In demented elders, however, one can see diffuse slow waves in the delta and theta frequencies.

Normal elders show normal sleep patterns with certain modifications (Box 51.1). The delta waves during slow-wave sleep (SWS) are reduced in amplitude and incidence [27, 59, 60]. The amplitude of delta waves decreases, and therefore, in the standard scoring technique, SWS decreases. Feinberg et al. [61] discussed this point and suggested that quantification of the amount of time spent in a specified frequency be used for scoring SWS in elderly individuals, rather than using an amplitude criterion. Mann and Roschke [62] in a later study using EEG frequency and cross-correlation analysis in a group of 59 healthy young and middle-aged men confirmed a significant decline of the delta/theta bands during NREM sleep but an increase in EEG power in beta frequency during rapid eye movement (REM) sleep with increasing age. Recent authors [63–65] also commented on the age-related decline in slow waves. Mander et al. [64] thought that prefrontal atrophy, disrupted NREM slow waves, and hippocampal-dependent memory in aging are all interrelated. Colrain and co-investigators reported a linear decline in amplitude of sleep-evoked delta waves across the adult lifespan. This reduction in amplitude of delta waves could be related to the following factors: (1) reduction in neuronal synchronization in the neocortex [27, 58], (2) alterations in the skull [27, 60], (3) changes in the subarachnoid spaces [27, 60], (4) reduction in specific subpopulation(s) of neurons [66], (5) a steady decline of synaptic density resulting in a decline of intracerebral connectivity [67], and (6) changes in receptor functions and neurochemical alterations affecting synaptic communication and connectivity [68].

Sleep spindles may show a variety of changes in old age [69–71], including decreased frequency, amount, and amplitude. The frequency may decrease from 16 to 14 Hz, and then from 14 to 12 Hz. The spindles are often poorly formed and poorly developed. Sleep spindle changes thus resemble those noted with alpha frequency in old age.

The cyclic pattern from REM to NREM remains unchanged, but the first cycle may be reduced [27, 72, 73]. REM density (i.e., number of eye movement bursts per minute of REM sleep) and total REM sleep time are reduced, but the percentage of REM in relation to total sleep time (TST) remains unaltered [27, 74, 75]. Sleep fragmentation is due to frequent interruptions at night. In addition, there are frequent sleep stage shifts and, thus, frequent awakenings [27, 56]. Regarding nocturnal TST (lights out to lights on), there is discrepancy between subjective report and objective data based on the technician’s schedule [27].

Nighttime sleep of elders usually is reported to be decreased (e.g., 5.5–6.5 h, in contrast to the usual 7.5–8.0 h TST average of young adults) [76]. This may not be an accurate observation, because elders often take daytime naps; 24-h TST of elders probably is no different from the 24-h TST of young adults.

Increased fragmentation of sleep and increased numbers of transient arousals accompanied by increased daytime sleepiness have been described in the studies by Carskadon et al. [77], Carskadon and Dement [78], and Boselli et al. [79]. Kales et al. [80] and Feinberg et al. [59] demonstrated the following changes in sleep with advancing age: state changes; frequent stage shifts; reduction in SWS and the EEG amplitude of delta waves; and increased NREM stage 1 owing to frequent arousals, decreased total nocturnal sleep, and reduction in total REM sleep time but normal REM percentage in relation to the TST.

Williams et al. [81] recruited 120 healthy seniors through advertisements, without mentioning sleep. They tried to carefully screen out sleep disorders by excluding those who had sleep complaints. These authors found that the seniors’ sleep quality was poorer than that of young individuals. In particular, there was a decrease in stages 3 and 4 sleep and an increase in nighttime wakefulness [81, 82]. Prinz and Vitiello [83] considered these findings as a benchmark level of sleep change associated with aging per se. In another study involving the Veterans Administration Survey, Cashman et al. [84] found that nighttime hypoxemia, which correlated with sleep apnea, was worse in several medical disorders (i.e., diabetes, cardiovascular disease, history of alcoholism, and vascular headaches). Thus, the data suggest that the disease states may interact with sleep disorders.

Between the ages of 60 and 90 years, there are differences in the sleep architecture of men and women [71, 85]. Between 60 and 70 years, men have more frequent arousals and more decrements in slow-wave sleep. Between 60 and 80 years, women spend 9 % of TST in the slow-wave stage, whereas men spend only 2 %. The percentages of REM and total REM sleep are not different for men and women between 60 and 90 years. In a meta-analysis of normative sleep data across the human life span, Ohayon et al. [86] also reported a reduction in SWS beginning in middle age, with complete absence after the age of 90 years. In a recent population-based cross-sectional Sao Paulo epidemiological study [87, 88] including 1042 individuals (468 men and 574 women) with an age range of 20–80 years, Moraes et al. [87] noted after polysomnographic (PSG) study that their findings were similar to those of Ohayon et al. [86] except that the reduction in SWS percentage correlated with age in men but not in women, whereas the reduction in REM sleep percentage correlated with age in women but not in men.

In a longitudinal PSG and diary-based study, Hoch et al. [89] found deterioration of measures of sleep quality, continuity, and depth but not other sleep measures over a 3-year follow-up period in a group of 27 healthy “old old” subjects (75–87 years) as contrasted with a group of 23 “young old” subjects (61–74 years). The decline in sleep measures was manifested by impaired sleep efficiency, prolonged sleep latency, increased wakefulness after sleep onset, and decreased SWS percentage. These changes were accompanied by increased napping in the “old old” group.

Circadian rhythm changes [85, 90] in the elderly result from fundamental changes in social activity, including family interaction. Interaction is governed by alterations of daily routine and activities, health needs, and psychosocial factors (e.g., loneliness, divorce) [27]. There may also be intrinsic changes in the circadian rhythm related to the pathologic changes noted in apparently normal individuals. Animal studies lend support to this conclusion [91–95]. In long-term care facilities, circadian rhythm disturbances may be related to alterations in Zeitgebers (external time cues), such as bedtime, medication time, mealtime, and special institutional regulations on lights out and lights on [17]. Wessler et al. [96] made an intensive study of 69- to 94-year-old institutionalized patients under strict environmentally controlled conditions and found a remarkable regularity in circadian synchronization. In a study involving 69- to 86-year-old subjects, however, Scheving et al. [97] did not find support for the other group’s conclusion. In all of these studies involving institutionalized patients, the effect of chronic illnesses must be considered in explanations of circadian rhythm disturbances. Thus, these changes may not be related to “normal” old age.

A study of evolution of sleep shows that the strong monophasic circadian rhythm of youth gives way to a polyphasic ultradian rhythm in old age. Frequent awakenings at night, with reduction in wakefulness, are accompanied by increased daytime naps. These physiologic changes may be related to the structural alterations noted in the suprachiasmatic nucleus (SCN) and brain stem hypnogenic neurons in experimental studies in several species of animals [98–100]. The human central circadian clock in the suprachiasmatic nucleus is subject age-associated changes [101] (e.g., molecular rhythms, ion channels, neurotransmitters, intracellular messenger); however, little is known about the underlying mechanisms. These changes may cause a reduction in the amplitude of the circadian timing signal, a deduction in amplitude of daily rhythms in physiology and a weakening of the peripheral oscillators. These changes partly explain some of the sleep disturbances in the elderly.

There is also phase advance in the elderly—that is, there is a tendency to go to sleep early and awaken early. These changes may be related to age-related changes in the core body temperature rhythm [102, 103]. In elderly individuals, the amplitude of the temperature rhythm is attenuated and phase-advanced [103].

There are striking functional and structural changes noted in the elderly in the ANS [27, 28, 104–107]. Changes are found in autonomic nerves and ganglia; ANS-controlled cardiovascular, respiratory, and gastrointestinal functions; sympathetic nerve activity; thermoregulation; and nocturnal penile tumescence in men. The age-related structural alterations in the human superior cervical ganglia may explain the deterioration of neuronal functional capacity and affect neuronal plasticity and regenerative characteristics [106].

Despite some inconsistent early findings [5], there is a direct relationship between normal aging, CBF, and cerebral metabolism. The xenon-133 inhalation method related a clear-cut decline in the regional blood flow exclusively to advancing age, without the confounding factors of associated diseases [139, 140]. This decline with advancing age was noted more in the gray than in the white matter CBF values. Maximal declines were seen in the prefrontal and parietal regions and minimal declines in the frontal and frontotemporal regions [5]. This decline in old age seems to be related to a progressive decrease in the cerebral metabolic rate [141] and possibly also to the morphologic changes in the neurons in the brains of elderly individuals. It should be noted that the decrease in CBF during SWS and the increase during REM sleep are similar in normal subjects of all ages. In elderly sleep apnea patients, however, this decrease during SWS becomes excessive, placing elderly individuals at increasing risk for sudden death and development of stroke during sleep when combined with hypoxemia related to apnea.

Aging represents biologic maturation, which may be accompanied by a variety of pathologic changes in the CNS. The neuropathologic changes of old age can be summarized as follows [5, 142]: Shrinkage of the brain; alterations in the outline; and loss of neurons in various locations; lipofuscin accumulation; collection of corpora amylacea; intraparenchymal vascular changes; loss of dendritic arbor and dendritic spines; and presence of senile plaques, amyloid deposits, neurofibrillary tangles, granulovacuolar degeneration, and Hirano bodies. The presence of senile plaques, amyloid deposits, neurofibrillary tangles, granulovacuolar degeneration, and Hirano bodies is correlated with dementia, but the other neuropathologic changes are considered nonspecific changes of aging.

From the standpoint of sleep disorders medicine, the cell loss in the locus coeruleus, pontine and midbrain reticular formation, selective hypothalamic regions, and SCN, as well as accumulation of neurofibrillary tangles and abnormal pigment in the hypothalamus, are important morphologic correlates for widespread sleep disturbances in the elderly. Animal experiments on the SCN show the relationship between destruction of these nuclei and alteration of circadian rhythmicity of adrenal cortical secretion, body temperature, activity–rest cycle, and sleep cycle loss [27].

In an epidemiologic study, Ford and Kamerow [143] interviewed 7954 subjects and observed that 40 % of patients with insomnia and 46.5 % of those with hypersomnia had a psychiatric disorder, compared with 16 % of those with no sleep complaints. Complaints of persistent insomnia are important late in life. There is a high incidence of depression with insomnia in the elderly. Among the 1801 elderly respondents aged 65 and older, the prevalence of insomnia was 12 % and the incidence of insomnia was 7.3 % [143]. For hypersomnia, the figures for prevalence and incidence were 1.6 and 1.8 %, respectively. There was a strong association between persistent insomnia (longer than 1 month) and the risk of major depression. Clayton et al. [144] noted that, in late-life spousal bereavement, there is also a persistent and debilitating complaint of insomnia.

Brabbins et al. [145] noted an overall prevalence of 35 % for insomnia complaints (more in women) after an interview of 1070 noninstitutionalized elderly individuals. In contrast, after interviewing 59 institutionalized and 874 community-dwelling residents, Henderson et al. [146] found a prevalence of approximately 12 % in the institutionalized and approximately 16 % among the community-dwelling elderly at 70 years or older. Insomnia complaints are more prevalent among women; whites; and those with depression, pain, and poor health. In another study from Germany, Stepnowsky et al. [147] investigated the prevalence of insomnia in 330 patients older than 65 years attending the offices of five general practitioners. Using the Diagnostic and Statistical Manual of Mental Disorders (3rd revision) diagnostic criteria, they found severe insomnia in 23 %, moderate insomnia in 17 %, and mild insomnia in another 17 % of the patients. There was a significant association between insomnia, depression, and dementia.

Foley et al. [148] conducted an important epidemiologic study limited to interviews in more than 9000 elderly subjects aged 65 years and older from three communities in the United States in the National Institute on Aging’s multicentered study entitled “Established Populations for Epidemiologic Studies of the Elderly”. These authors observed at least one of the following complaints in over half the subjects: trouble falling asleep, multiple awakenings, early morning awakening, daytime naps, and tiredness. These complaints are more common in women than in men and are often associated with respiratory symptoms, depression, nonprescription and prescription medications, poor self-esteem, and physical disabilities. The authors observed 33 % of men and 19 % of women with snoring and 13 % of men and 4 % of women with observed apneas. In this cross-sectional study, the authors did not find a clear relationship of loud snoring, observed apneas, or daytime sleepiness to hypertension or cardiovascular disease in the elders. In a later epidemiologic study of 6800 persons over 3 years, Foley et al. [149] reported that 28 % of older adults had complaints of chronic insomnia but, in the absence of risk factors (e.g., depression, medical disorders, circadian rhythm disorders, medications), only 7 % had insomnia. In a 2003 National Sleep Foundation Sleep in America poll, sleep complaints common in older adults are found to be secondary to comorbidities rather than aging per se [149].

Excessive daytime somnolence (EDS) is often associated with fragmentation of nocturnal sleep, which may have been due to sleep-disordered breathing and periodic leg movements in sleep (PLMS) [150]. Other factors are changes in the circadian rhythms of temperature, alertness and sleepiness, and social time cues. Frequent daytime sleepiness in older adults is associated with an impairment of physical functioning and decreased exercise frequency [151]. Based on the National Sleep Foundation 2003 Sleep in America poll, Foley et al. [148] reported frequent napping associated with EDS, depression, pain, and nocturia in older adults.

Many other factors can disrupt sleep: Nocturia, leg cramps, pain, coughing or difficulty in breathing, temperature sensitivity, and dreams [149, 150]. There is an increased prevalence of nocturia in the elderly causing sleep disturbance [151–153]. Sleep disturbances, particularly complaints of insomnia, may contribute to increasing risk of falls and fractures in the elderly [150, 154–157]. There is controversy whether the increasing risk of falls in the elderly is related to the sleep disturbance per se or greater use of hypnotics by the elderly [154]. In a multicenter community-dwelling questionnaire-based study involving over 8000 white women aged 69 and older (mean = 77 years), self-reported long sleep (at least 10 h per 24 h) and daily napping were associated with greater risk of falls and fractures [155]. In a recent [157] prospective observational sleep study in 3101 community-dwelling men aged 67 and above (mean = 76 years), Stone et al. reported that subjective (Epworth Sleepiness Scale and Pittsburgh sleep quality index) and objective (actigraphy and in-home polysomnography) sleep disturbances were associated with risk of falls in older men, independent of confounders. These authors found that reduced hours of sleep (five hours or less compared with those with seven to eight hours) and nocturnal hypoxemia (≥10 of sleep time with arterial oxygen saturation <90 %) but not apnea–hypopnea index were associated with greater risk of falls.

Vitiello and Prinz [158] found that CNS degenerative disorders (e.g., dementia of the Alzheimer’s type) may cause polyphasic sleep–wake patterns, which constitute a significant problem among old nursing home residents. In demented elderly subjects, nocturnal agitation, night wandering, shouting, and incontinence contribute to a variety of sleep disturbances. There are many other factors in the pathogenesis of nocturnal agitation, including loss of social Zeitgebers and circadian timekeeping, sleep apnea, REM-related parasomnias, low ambient light, and cold sensitivity [159].

An important behavioral disturbance during sleep late in life is snoring [150]. According to Koskenvuo et al. [160, 161], habitual snoring was found in 9 % of men and 3.6 % of women ages 40–69 years in their study done in Finland. Hypertension, ischemic heart disease, and stroke are risk factors for snoring. In an epidemiologic survey, Lugaresi et al. [162] found that approximately 60 % of men and 40 % of women between the ages of 41 and 64 years were habitual snorers. Enright et al. [163] recruited 5201 adults ages 65 and older who were participants in a cardiovascular health study that enrolled a random sample of Medicare subjects in four US communities. In this study, there was no positive correlation between aging and self-reported snoring. Loud snoring, however, was independently associated with body mass index, diabetes mellitus, and arthritis in older women, and with alcohol use in elderly men.

What is the relationship between sleep duration and mortality in elders? In 1989, Ancoli-Israel [164] re-examined the 1979 data of Kripke et al. [165] and concluded that 86 % of deaths associated with short (<7 h) or long (>8 h) sleep occurred among those older than 60 years. Thus, it could be concluded by extrapolation from these data that older individuals who sleep less than 5 h or more than 9 h may be at greater risk for death.

The high frequency of sleep complaints in aged individuals may be related to the physiologic sleep changes of normal aging as well as to concomitant medical, psychiatric, neurologic, and other disorders that are prevalent in this group [54, 85, 149, 153, 154, 159, 166]. Subjective sleep complaints are common in older subjects, as many reports attest [167–170]. The subjective complaints were corroborated by objective laboratory data. In contrast to the increasing incidence of subjective complaints from women, however, elderly men had more sleep disturbances than elderly women by objective reports [171].

Clinical assessment consists of a sleep, medical, drug, and psychiatric history. A general approach for making a clinical assessment is described in Chap. 26; only the points relevant to elders are emphasized in this section.

It is well known that the prevalence and intensity of sleep disturbances increase with age [149, 150, 179, 181–183]. Factors that affect the prevalence of sleep disturbances in the elderly are (1) physiologic (e.g., age-related changes in sleep patterns); (2) medical; (3) psychiatric; (4) pharmacologic (e.g., use, misuse, and abuse of drugs); and (5) social (changing rest–activity schedules, and, therefore, sleep–wake patterns) [149, 150, 179–185].

The prevalence of sleep-related breathing disorders, PLMS, and snoring are all greater among elders. The prevalence of sleep apnea increases with age and is greater in men than in women, and in menopausal women than in premenopausal women [164]. There is controversy over the exact prevalence of sleep apnea in the older population. The prevalence rates for sleep apnea—defined as repetitive episodes of upper airway obstruction—in elders in various studies have been estimated to range from 5.6 to 70 % [164, 186–194]. The prevalence is greater in the elderly than in younger adults, and in men than in women [195, 196]. There is a lack of consistency in study methods, so it is very difficult to generalize from these studies. In the Sleep Heart Health study involving a large cohort of about 6400 subjects (aged 40–98 years, with a mean of 63.5), Young et al. [194] reported an increased prevalence of SAS by 10-year age groups: 32 % of those ages 60–69 years had an apnea–hypopnea index (AHI) of 5–14 and 19 % had an AHI of ≥15; 33 % of those ages 70–79 years had an AHI of 5–14 and 21 % had an AHI of ≥15; and 36 % of those ages 80–98 years had an AHI 5–14; and 20 % had an AHI of ≥15. Thus, there was a small increase in the AHI index by 10-year age groups. In an earlier study, Hoch et al. [188] also found increased AHI and prevalence of SAS from 60 to 90 years. It should be noted, however, that based on a definition of 15 or more apneas or hypoapneas per hour of sleep accompanied by EDS, the recent Wisconsin sleep cohort study data listed prevalence of moderate-to-severe SAS at 10 % in men and 3 % in women among 30–49 years, but 17 % in men and 9 % in women among 50–70 years [197]. Because of the high prevalence of SAS in elders, questions have been raised as to the significance of sleep-disordered breathing in the elderly. Prinz et al. [198] stated that, because apneic episodes in the elderly may not have the same clinical symptoms as noted in younger people, it is more difficult to determine whether further investigations are needed. Fleury [199], suggested that SAS in the elderly not be considered different from SAS in middle-aged men, however, assuming that an appropriate diagnostic apnea index (AI) or respiratory disturbance index (RDI) was taken into consideration. Ancoli-Israel and Coy [193] agreed that, if SAS is severe enough to cause symptoms in the elderly, treatment should be similar to that in a younger patient.

The controversy as to whether SAS in the elderly represents a specific entity or the same disease in younger subjects continues [150, 200–202]. Further research is needed to resolve this issue. Launois et al. [201] contended that untreated SAS in the elderly appears to have less impact on mortality than in middle-aged adults; however, symptomatic elderly SAS patients tolerate continuous positive airway pressure (CPAP) as well as the younger patients. Based on a retrospective study in Poland, Bielicki et al. [202] concluded that SAS is more frequent in elderly than in younger patients but is more severe in younger patients requiring higher CPAP titration pressure. In an important longitudinal follow-up study of elderly patients with SAS for 18 years, Ancoli-Israel et al. [203] observed that the AHI did not continue to increase if the patient’s body mass index remained stable. Some of the risk factors predisposing the elderly to SAS are as follows [204, 205]: age, gender, obesity, smoking, family history, race, upper airway anatomic configuration, use of sedative hypnotics, and alcohol consumption.

Reasons for the variation in the prevalence of sleep apnea could be the sampling of different populations without using a random sampling method, small sample size, or the use of different criteria to define sleep apnea. An important problem has been the scoring criteria for apnea and hypopnea and the definition of AI, AHI, or RDI. In the current American Academy of Sleep Medicine guidelines for scoring [206], these questions have been addressed and standardized (see Chap. 25). Another problem has been the clinical significance of an AI or RDI of 5. Some authors have suggested that an AI of 20 or more is related to increased risk of death [207]. In a survey among 427 randomly selected community-dwelling people, 65–95 years of age, in San Diego, California, Ancoli-Israel et al. [186] reported that 81 % of the subjects had an AHI of ≥5 with a prevalence rate of 62 % for an AHI of ≥10, 44 % for an AHI of ≥20, and 24 % for an AHI of ≥40. Night-to-night variability in sleep apnea has been the other confounding problem in the elderly [186, 208–211].

The question of the relationship between sleep apnea or sleep-disordered breathing and increased morbidity or mortality remains controversial, several studies, however, have found a positive relationship [207, 212, 213]. In a nearly 10-year follow-up of a randomly selected, population-based probability sample of 426 men and women (65–95 years old), Ancoli-Israel et al. [214] found that those with severe sleep-disordered breathing (RDI of 30 or more) had a significantly shorter survival but that the RDI was not an independent predictor of death. Similar results were reported from a sleep disorders clinic patient population study by Lavie et al. [215], Ancoli-Israel et al. [214] stated that other confounding variables such as age, hypertension, and cardiovascular or pulmonary disease might be responsible for the increased morbidity and mortality. Chronologic or biological age (determined by biological markers of physiologic aging) may be the single most important factor for increased morbidity and mortality in sleep-disordered breathing (i.e., sleep apnea may be an age-dependent condition). To address this controversy, well-designed controlled clinical studies are needed.

The diagnostic evaluation should begin with a thorough history of sleep disturbances, which may be EDS, difficulty initiating or maintaining sleep, and intrusions of unusual behavior during sleep. Physical examination may direct attention to systemic disease. Based on the history and findings of the physical examination, a decision should be made regarding referrals to specialized sleep centers for PSG and MSLT studies. Tests should be performed when clinical interview and examination cannot resolve the problems.

Most of the sleep disturbances of elders can be diagnosed by a careful history and physical examination. For some conditions, however, laboratory assessment is important. In SAS, it is important to have an all-night PSG study to quantify and determine the severity of sleep-related respiratory disturbances. Sleep apnea is a treatable condition, so it is important to make this diagnosis correctly. In addition, MSLT and PSG studies are important for a narcolepsy diagnosis, although in elderly people this diagnosis may have been made many years earlier. All-night video recordings are necessary to diagnose some conditions, such as RBD, that require the examiner to differentiate from among a number of sleep disorders with similar symptoms. Appropriate tests should be performed if other medical or neurologic disorders are suspected.

The objective of treatment is to reduce the risk of mortality and morbidity and improve quality of life (Box 51.3) [279]. The first step is accurate assessment and diagnosis.