Phyllis C. Zee

Evidence-Based Recommendations for the Assessment and Management of Sleep Disorders in Older Persons

Sleep‐related disorders are most prevalent in the older adult population. A high prevalence of medical and psychosocial comorbidities and the frequent use of multiple medications, rather than aging per se, are major reasons for this. A major concern, often underappreciated and underaddressed by clinicians, is the strong bidirectional relationship between sleep disorders and serious medical problems in older adults. Hypertension, depression, cardiovascular disease, and cerebrovascular disease are examples of diseases that are more likely to develop in individuals with sleep disorders. Conversely, individuals with any of these diseases are at a higher risk of developing sleep disorders. The goals of this article are to help guide clinicians in their general understanding of sleep problems in older persons, examine specific sleep disorders that occur in older persons, and suggest evidence‐ and expert‐based recommendations for the assessment and treatment of sleep disorders in older persons. No such recommendations are available to help clinicians in their daily patient care practices. The four sections in the beginning of the article are titled, Background and Significance, General Review of Sleep, Recommendations Development, and General Approach to Detecting Sleep Disorders in an Ambulatory Setting. These are followed by overviews of specific sleep disorders: Insomnia, Sleep Apnea, Restless Legs Syndrome, Circadian Rhythm Sleep Disorders, Parasomnias, Hypersomnias, and Sleep Disorders in Long‐Term Care Settings. Evidence‐ and expert‐based recommendations, developed by a group of sleep and clinical experts, are presented after each sleep disorder.

Aerobic exercise improves self-reported sleep and quality of life in older adults with insomnia

OBJECTIVE To assess the efficacy of moderate aerobic physical activity with sleep hygiene education to improve sleep, mood and quality of life in older adults with chronic insomnia. METHODS Seventeen sedentary adults aged >or=55 years with insomnia (mean age 61.6 [SD±4.3] years; 16 female) participated in a randomized controlled trial comparing 16 weeks of aerobic physical activity plus sleep hygiene to non-physical activity plus sleep hygiene. Eligibility included primary insomnia for at least 3 months, habitual sleep duration <6.5h and a Pittsburgh Sleep Quality Index (PSQI) score >5. Outcomes included sleep quality, mood and quality of life questionnaires (PSQI, Epworth Sleepiness Scale [ESS], Short-form 36 [SF-36], Center for Epidemiological Studies Depression Scale [CES-D]). RESULTS The physical activity group improved in sleep quality on the global PSQI (p<.0001), sleep latency (p=.049), sleep duration (p=.04), daytime dysfunction (p=.027), and sleep efficiency (p=.036) PSQI sub-scores compared to the control group. The physical activity group also had reductions in depressive symptoms (p=.044), daytime sleepiness (p=.02) and improvements in vitality (p=.017) compared to baseline scores. CONCLUSION Aerobic physical activity with sleep hygiene education is an effective treatment approach to improve sleep quality, mood and quality of life in older adults with chronic insomnia.

Role of sleep timing in caloric intake and BMI

Sleep duration has been linked to obesity and there is also an emerging literature in animals demonstrating a relationship between the timing of feeding and weight regulation. However, there is a paucity of research evaluating timing of sleep and feeding on weight regulation in humans. The goal of this study was to evaluate the role of sleep timing in dietary patterns and BMI. Participants included 52 (25 females) volunteers who completed 7 days of wrist actigraphy and food logs. Fifty‐six percent were “normal sleepers” (midpoint of <5:30 am) and 44% were “late sleepers” (midpoint of sleep ≥5:30 am). Late sleepers had shorter sleep duration, later sleep onset and sleep offset and meal times. Late sleepers consumed more calories at dinner and after 8:00 pm, had higher fast food, full‐calorie soda and lower fruit and vegetable consumption. Higher BMI was associated with shorter sleep duration, later sleep timing, caloric consumption after 8:00 pm, and fast food meals. In multivariate models, sleep timing was independently associated with calories consumed after 8:00 pm and fruit and vegetable consumption but did not predict BMI after controlling for sleep duration. Calories consumed after 8:00 pm predicted BMI after controlling for sleep timing and duration. These findings indicate that caloric intake after 8:00 pm may increase the risk of obesity, independent of sleep timing and duration. Future studies should investigate the biological and social mechanisms linking timing of sleep and feeding in order to develop novel time‐based interventions for weight management.

The Impact of School Daily Schedule on Adolescent Sleep

Objectives. This study was initiated to examine the impact of starting school on adolescent sleep, to compare weekday and weekend sleep times, and to attempt to normalize the timing of the circadian sleep/wake cycle by administering bright light in the morning. This was a collaborative project involving high school students and their parents, as well as high school and university faculty members, for the purpose of contributing information to the scientific community while educating students about research processes and their own sleep/wake cycles and patterns. Methods. Sixty incoming high school seniors kept sleep/wake diaries beginning in August and continuing through 2 weeks after the start of school in September. Sleep diaries were also kept for 1 month in November and 1 month in February. Early-morning light treatments were given to 19 students in the last 2 weeks of November and the last 2 weeks of February. Neuropsychologic performance was measured with computer-administered tests. Paper-and-pencil tests were used for assessment of mood and vigor. A testing period consisted of 2 consecutive days at the beginning and end of November and at the beginning and end of February. Tests were given 3 times per day, ie, in the morning before school (6:30–8:00 am), during midday lunch periods (11:30 am to 1:00 pm), and in the afternoon (3:00–4:30 pm), on each of the test days. Results. Adolescents lost as much as 120 minutes of sleep per night during the week after the start of school, and weekend sleep time was also significantly longer (∼30 minutes) than that seen before the start of school (August). No significant differences were found between weekday sleep in the summer and weekend sleep during the school year. Early-morning light treatments did not modify total minutes of sleep per night, mood, or computer-administered vigilance test results. All students performed better in the afternoon than in the morning. Students in early morning classes reported being wearier, being less alert, and having to expend greater effort. Conclusions. The results of this study demonstrated that current high school start times contribute to sleep deprivation among adolescents. Consistent with a delay in circadian sleep phase, students performed better later in the day than in the early morning. However, exposure to bright light in the morning did not change the sleep/wake cycle or improve daytime performance during weekdays. Both short-term and long-term strategies that address the epidemic of sleep deprivation among adolescents will be necessary to improve health and maximize school performance.

Sleep: a health imperative.

Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is a growing and underappreciated determinant of health status. Sleep deprivation contributes to a number of molecular, immune, and neural changes that play a role in disease development, independent of primary sleep disorders. These changes in biological processes in response to chronic sleep deficiency may serve as etiological factors for the development and exacerbation of cardiovascular and metabolic diseases and, ultimately, a shortened lifespan. Sleep deprivation also results in significant impairments in cognitive and motor performance which increase the risk of motor vehicle crashes and work-related injuries and fatal accidents. The American Academy of Sleep Medicine and the Sleep Research Society have developed this statement to communicate to national health stakeholders the current knowledge which ties sufficient sleep and circadian alignment in adults to health.

Sleep Disturbances in Pregnancy

OBJECTIVE: To estimate the prevalence and patterns of sleep disturbances during pregnancy among healthy nulliparous women. METHODS: This was a prospective, cohort study of healthy nulliparous women, recruited between 6 and 20 weeks of gestation, who completed a baseline sleep survey at enrollment with follow-up in the third trimester. The survey was composed of the following validated sleep questionnaires: Berlin Questionnaire for Sleep Disordered Breathing, Epworth Sleepiness Scale, National Institutes of Health/International Restless Legs Syndrome Question Set, Women’s Health Initiative Insomnia Rating Scale, and the Pittsburgh Sleep Quality Index. Differences in sleep characteristics between the baseline and third trimester were compared using the paired t test or McNemar test for continuous or categorical data, respectively. RESULTS: One hundred eighty-nine women completed both baseline and follow-up sleep surveys. The mean gestational age was 13.8 (±3.8) and 30.0 (±2.2) weeks at the first and second surveys, respectively. Compared with the baseline assessment, mean sleep duration was significantly shorter (7.4 [±1.2] hours compared with 7.0 [±1.3] hours, P<.001), and the proportion of patients who reported frequent snoring (at least three nights per week) was significantly greater (11% compared with 16.4%, P=.03) in the third trimester. The percentage of patients who met diagnostic criteria for restless leg syndrome increased from 17.5% at recruitment to 31.2% in the third trimester (P=.001). Overall poor sleep quality, as defined by a Pittsburgh Sleep Quality Index score greater than 5, became significantly more common as pregnancy progressed (39.0% compared with 53.5%, P=.001). CONCLUSION: Sleep disturbances are prevalent among healthy nulliparous women and increase significantly during pregnancy. LEVEL OF EVIDENCE: II

Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease

Shift work is associated with increased cardiovascular morbidity and mortality. Whereas it has been suggested that continuous shifting of the circadian clock/sleep-wake cycle may have negative effects on health, there is very little experimental evidence to support such a hypothesis. Cardiomyopathic Syrian hamsters were either maintained on a fixed light-dark (LD) cycle (n = 31) or were subjected to a 12-h phase shift in the LD cycle on a weekly basis (n = 32). The duration of the life span was recorded for each animal. Chronic reversal of the external LD cycle at weekly intervals resulted in a significant decrease in the survival time in cardiomyopathic hamsters with the median life span being reduced by 11%. Disrupting normal circadian rhythmicity in an animal susceptible to early mortality due to cardiac disease results in a further decrease in longevity. The deleterious effects of the chronic phase shifts in the LD cycle in cardiomyopathic hamsters may be related to reports of increased cardiovascular morbidity and mortality in humans engaged in shift work.Shift work is associated with increased cardiovascular morbidity and mortality. Whereas it has been suggested that continuous shifting of the circadian clock/sleep-wake cycle may have negative effects on health, there is very little experimental evidence to support such a hypothesis. Cardiomyopathic Syrian hamsters were either maintained on a fixed light-dark (LD) cycle ( n = 31) or were subjected to a 12-h phase shift in the LD cycle on a weekly basis ( n = 32). The duration of the life span was recorded for each animal. Chronic reversal of the external LD cycle at weekly intervals resulted in a significant decrease in the survival time in cardiomyopathic hamsters with the median life span being reduced by 11%. Disrupting normal circadian rhythmicity in an animal susceptible to early mortality due to cardiac disease results in a further decrease in longevity. The deleterious effects of the chronic phase shifts in the LD cycle in cardiomyopathic hamsters may be related to reports of increased cardiovascular morbidity and mortality in humans engaged in shift work.

A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: The HomePAP study

STUDY OBJECTIVES To test the utility of an integrated clinical pathway for obstructive sleep apnea (OSA) diagnosis and continuous positive airway pressure (CPAP) treatment using portable monitoring devices. DESIGN Randomized, open-label, parallel group, unblinded, multicenter clinical trial comparing home-based, unattended portable monitoring for diagnosis and autotitrating CPAP (autoPAP) compared with in-laboratory polysomnography (PSG) and CPAP titration. SETTING Seven American Academy of Sleep Medicine (AASM) accredited sleep centers. PARTICIPANTS Consecutive new referrals, age 18 yr or older with high probability of moderate to severe OSA (apnea-hypopnea index [AHI] ≥ 15) identified by clinical algorithm and Epworth Sleepiness Scale (ESS) score ≥ 12. INTERVENTIONS Home-based level 3 testing followed by 1 wk of autoPAP with a fixed pressure CPAP prescription based on the 90% pressure from autotitration of PAP therapy (autoPAP) device (HOME) compared with attended, in-laboratory studies (LAB). MEASUREMENTS CPAP acceptance, time to treatment, adherence at 1 and 3 mo; changes in ESS, and functional outcomes. RESULTS Of 373 participants, approximately one-half in each study arm remained eligible (AHI ≥ 15) to continue in the study. At 3 mo, PAP usage (nightly time at pressure) was 1 hr greater: 4.7 ± 2.1 hr (HOME) compared with 3.7 ± 2.4 hr (LAB). Adherence (percentage of night used ≥ 4 hr) was 12.6% higher: 62.8 ± 29.2% compared with 49.4 ± 36.1% in the HOME versus LAB. Acceptance of PAP therapy, titration pressures, effective titrations, time to treatment, and ESS score change did not differ between arms. CONCLUSIONS A home-based strategy for diagnosis and treatment compared with in-laboratory PSG was not inferior in terms of acceptance, adherence, time to treatment, and functional improvements. TRIAL REGISTRATION http://www.ClinicalTrials.gov; Identifier: NCT: 00642486.

Cross-Sectional Associations Between Measures of Sleep and Markers of Glucose Metabolism Among Subjects With and Without Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Sleep Study

OBJECTIVE To examine whether sleep duration and quality are associated with fasting glucose, fasting insulin, or estimated insulin resistance in a community-based sample of early middle-aged adults. RESEARCH DESIGN AND METHODS This was an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Habitual sleep duration and fragmentation were estimated from 6 days of wrist actigraphy collected in 2003–2005. Insomnia was defined as self-reported difficulty falling asleep or waking up in the night three or more times per week plus average sleep efficiency of <80% based on actigraphy. Fasting blood samples to measure glucose and insulin were collected after the sleep measures during the CARDIA clinical examination in 2005–2006. Insulin resistance was estimated using the homeostatic model assessment (HOMA) method. Analyses were cross-sectional and stratified by the presence of diabetes. RESULTS There was no association between sleep measures and fasting glucose, insulin, or HOMA in the 115 subjects without diabetes. Among the 40 subjects with diabetes, after adjustment for covariates, 10% higher sleep fragmentation was associated with a 9% higher fasting glucose level, a 30% higher fasting insulin level, and a 43% higher HOMA level. Insomnia was associated with a 23% higher fasting glucose level, a 48% higher fasting insulin level, and an 82% higher HOMA level. CONCLUSIONS The observed association between poor sleep quality and higher glucose, insulin, and estimated insulin resistance among subjects with diabetes warrants further examination of the effect of sleep disturbances on glucose control in type 2 diabetes.

Regulation of Sleep and Circadian Rhythms

Introduction to Sleep and Circadian Rhythms, Phyllis C. Zee and Fred W. Turek Ontogeny of Sleep and Circadian Rhythms, Fred C. Davis, Marcos G. Frank, and H. Craig Heller Neural Control of Sleep, J. Allan Hobson Circadian and Homeostatic Control of Wakefulness and Sleep, Derk-Jan Dijk and Dale M. Edgar Influence of Light on Circadian Rhythmicity in Humans, Charles A. Czeisler and Kenneth P. Wright, Jr. Role of Melatonin in the Regulation of Sleep, Fred W. Turek and Charles A. Czeisler Melatonin and Circadian Rhythmicity in Vertebrates: Physiological Roles and Pharmacological Effects, David R. Weaver The Impact of Changes in Nightlength (Scotoperiod) on Human Sleep, Thomas A. Wehr Cellular and Molecular Mechanisms of Sleep, Tarja Porkka-Heiskanen and Dag Stenberg Cellular and Molecular Mechanisms of Circadian Rhythms in Mammals, Piotr Zlomanczuk and William J. Schwartz Molecular and Genetic Aspects of Sleep, Thomas S. Kilduff and Emmanuel Mignot Molecular Genetic Approaches to the Identity and Function of Circadian Clock Genes, Jonathan P. Wisor and Joseph S. Takahashi Circadian and Sleep Control of Hormonal Secretions, Eve Van Cauter and Karine Spiegel Relationships Between Sleep and Immune Function, James M. Krueger, Jidong Fang, and Rachael A. Floyd Intrinsic Disruption of Normal Sleep and Circadian Patterns, Scott S. Campbell Sleep and Circadian Rhythm Disorders in Aging and Dementia, Donald L. Bliwise Effects of Sleep and Circadian Rhythms on Performance, Julie Carrier and Timothy H. Monk Neurological Disorders Associated with Disturbed Sleep and Circadian Rhythms, Phyllis C. Zee and Zoran M. Grujic Psychiatric Disorders Associated with Disturbed Sleep and Circadian Rhythms, Daniel J. Buysse, Eric A. Nofzinger, Matcheri S. Keshavan, Charles F. Reynolds III, and David J. Kupfer