Sleep Medicine ConferenceAugust 2016
By Ben Best
Why do people need sleep? Sleep allows the brain to restore essential nutrients (like glycogen) and remove waste products1,2 (like the beta-amyloid protein that causes Alzheimer’s disease).3,4 Sleep replenishes proteins depleted during wakefulness.5 Sleep is important for memory consolidation. 6,7
Although the brain is approximately 2% of the body’s weight, it uses about 20% of the body’s energy.8 The major source of that energy is the molecule adenosine triphosphate (ATP).
With increasing hours of wakefulness, there are decreasing amounts of ATP and increasing amounts of adenosine from which the high-energy phosphates have been removed. Adenosine causes sleepiness.9 Caffeine blocks adenosine action, reducing sleepiness and increasing alertness, 10 while impeding learning and memory.11
How much sleep do people need? The need for sleep diminishes with age. During the first six months of life, infants sleep more than half the time.12 Medications account for many of the sleeping problems of the elderly,13 but healthy older adults (age 65-76) tolerate sleep deprivation better than young adults (age 18-29).14 More than half of sleep-related car accidents occur in drivers under age 30, compared to only 5% in drivers over age 65.14 Adolescents tend to go to bed late and sleep late when they are allowed to, but as people get older they tend to go to bed earlier and awaken earlier.15
Independent of diabetes and high blood pressure, men who slept less than 6 hours per night were found to have four times the risk of dying compared to those who slept more (although this effect was not seen in women).16 Young healthy adults randomized to spend 4, 6, or 8 hours in bed for 14 nights showed reduced cognitive performance in proportion to lack of sleep for those with bed times of 6 hours or less.17
Healthy adults who habitually sleep more than the minimum necessary to avoid sleepiness and impaired function have shown greater development of the cerebral cortex.18 However, many studies have shown that excessive sleep is associated with increased risk of dying, although this is controversial.19 Post-menopausal women sleeping more than 9 hours per night exhibited increased inflammation and blood clotting, which are risk factors for cardiovascular disease.20
One study showed that napping for 10 minutes improves alertness and cognitive performance over the subsequent 3 hours, whereas a 5-minute nap is of little benefit, and a 20-minute nap results in “sleep inertia,” which is the period of confusion, sleepiness, and disorientation that is experienced upon awakening from sleep.21 A 16-week supplementation of healthy children with 600 mg daily of the omega-3 fatty acid DHA improved their sleep (longer sleep with fewer awakenings).22
On June 6-10, 2015, I attended the annual meeting of the American Academy of Sleep Medicine and the Sleep Research Society in Seattle, Washington.
Effects of Sleep Loss
David Dinges, PhD, (Chief of the Division of Sleep and Chronobiology, Perelman School of Medicine, Philadelphia, Pennsylvania) studies the effects of sleep loss. Between 1985 and 2012, average nightly sleep time reported by American adults declined from 7.40 to 7.18 hours.23 The reported prevalence of insomnia among US adults increased from 17.5% in 2004 to 19.2% in 2012. The largest relative increases occurred among diabetics and those in the 25-34 age group.24 An estimated 15% of Americans sleep less than 6 hours per night.25 Dr. Dinges has demonstrated that healthy adults restricted to four hours sleep per night for five nights ate more food and gained weight.26 Sleep restriction has been shown to reduce blood levels of the satiety hormone leptin,27 and to increase the hunger-producing hormone ghrelin,28 thereby increasing appetite. Dr. Dinges also showed that an extended night of sleep following the five nights of restricted sleep was not adequate to restore alertness or prevent sleepiness.29
Rachel Leproult, PhD, (Researcher, Universite libre de Bruxelles, Brussels, Belgium) studies the relationship between diabetes and quantity or quality of sleep.30 In one of her studies, she found that persons who slept less than 5 or 6 hours per night had a 28% greater incidence of diabetes, those who had difficulty initiating sleep had a 57% greater incidence, and those who had difficulty maintaining sleep had an 84% greater incidence.31 Dr. Leproult conducted an experiment in which healthy adults were either simply restricted to less than 5 hours sleep per night for eight days, or restricted to less than 5 hours sleep combined with disruption of the 24-hour circadian rhythm cycle. Both groups showed increased inflammation and insulin resistance, but the effect was substantially greater when sleep restriction was combined with circadian disruption. Insulin sensitivity dropped 39% for those who were only sleep restricted, but more than 53% for those who also experienced circadian disruption.32
Circadian disruption due to flying across more than three time zones (“jet lag”) is most effectively treated by exposure to bright daylight in the morning, and administration of melatonin in the evening.33 In another experiment, Dr. Leproult asked healthy adults who normally sleep less than 7 hours per night to increase their time in bed by one hour per day. After 40 days the subjects showed substantially improved insulin sensitivity.34
Carol Everson, PhD, (Professor, Medical College of Wisconsin, Milwaukee, Wisconsin) has studied the effects of sleep deprivation in rats. She has shown that sleep deprivation weakens the immune system35 and increases pathogenic bacteria in rats.36 People sleeping less than 7 hours per night have been shown to be nearly 3 times more likely to develop a common cold than people who sleep 8 hours or more.37 Totally sleep-deprived rats will die within about two or four weeks, with over 20% weight loss.38 Dr. Everson subjected rats to 10 days of sleep restriction six times, separated by two days of rest each time. The rats lost 15% of their body weight despite eating more than the usual amount of food. Even after four months of recovery, the rats were consuming 20% more food and 35% more water.38 In another experiment, rats totally deprived of sleep for 10 days showed a 39% increase in oxidative DNA damage, particularly in the liver, where this damage was almost 2.5 times greater than in controls.39
Cognitive Effects of Sleep Deprivation
Hans van Dongen, PhD, (Research Professor, Washington State University, Spokane, Washington) has conducted experiments to determine the effects of sleep deprivation on cognitive performance.40 He has found that sleep deprivation hampers decision making under conditions of uncertainty and unexpected change,41 but that the hampered decisions were more due to reduced reaction time than to reduced judgement.42 He has also found evidence that an increase in the inflammatory cytokine TNF-alpha contributes to the impaired vigilance associated with sleep deprivation. 43 Other studies have shown not only that inflammatory cytokines increase after sleep loss,44 but that cytokines (including TNF-alpha) released during illness increase sleepiness (to induce recovery-promoting sleep).45
Objective Measures of Insomnia
Julio Fernandez-Mendoza, PhD, (Assistant Professor, Pennsylvania State University, Hershey, Pennsylvania) seeks objective measures of insomnia. He cited studies that 8%-10% of people suffer from chronic insomnia and that 20%-30% of people will be suffering from temporary insomnia at any given time.46 He notes that insomnia patients have higher levels of adrenalin-like compounds (catecholamines), higher oxygen consumption, and higher blood pressure than good sleepers.46 He has also found elevated stress hormone (cortisol) in the saliva of children aged 5-12 reported by parents to have insomnia.47 He has found that patients with severe insomnia were several times more likely to also be suffering from depression.48 And Dr. Fernandez-Mendoza reported that excessive daytime sleepiness (affecting up to 30% of people) is associated with obesity and weight gain.49
Kai Spiegelhalder, MD, PhD, (Insomnia researcher, Freiberg Institute for Advanced Studies, Freiberg, Germany) also has sought objective measures of insomnia. Chronic insomnia is generally defined based on subjective complaints of difficulty falling asleep or difficulty remaining asleep, along with daytime sleepiness and fatigue. For diagnosis of chronic insomnia, these complaints must persist for at least four weeks.50 Overall, women complain of insomnia more than men, with the difference rising after age 45.51 Electronic monitoring of brain, heart, skeletal muscle, and eye movements (polysomnography) shows less difference between good sleepers and those complaining of insomnia than the complaints would indicate.50 Nonetheless, there is evidence that those complaining of insomnia have higher heart rates, elevated cortisol (stress hormone), and greater brain glucose metabolism (indicating greater brain activity) during sleep.52 Inherited insomnia is associated with increased cortisol and decreased melatonin secretion.51 These quantitative indications of arousal in insomniacs form the basis of Dr. Spiegelhalder’s “hyper-arousal model of insomnia.” 50,53 Dr. Spiegelhalder has shown that patients complaining of insomnia put much greater effort into trying to fall asleep, which worsens the problem.54 He does not recommend benzodiazepine tranquilizers such as Librium® or Valium® for anything but short-term use because of declining effectiveness, increasing dependency, and memory impairment.55 Antihistamines and antidepressants are less addictive, but can have worse side effects, including liver and heart damage. Alcohol and barbiturates reduce the amount of time to fall asleep, but also reduce sleep quality.56,57 Prolonged-release melatonin supplementation has been shown to reduce insomnia in elderly patients without causing side effects.58,59 The main treatment Dr. Spiegelhalder recommends is Cognitive Behavioral Therapy for Insomnia (CBT-I).51
Cognitive Behavioral Therapy for Insomnia
Although Cognitive Behavioral Therapy for Insomnia (CBT-I) is often recommended by insomnia specialists as being the most safe and effective treatment, Simon Kyle, PhD, (Lecturer, University of Manchester, Manchester, England) has found that the therapy is not standardized, is poorly documented when used, and often fails to work.60 CBT-I can involve sleep diaries to identify thoughts or habits that cause sleep problems, relaxation training, using the bedroom only for sleep or sex, avoiding caffeine, nicotine, or alcohol, leaving the bedroom if sleep does not occur within ten minutes, and sleep restriction therapy. Dr. Kyle has concentrated his attention on sleep restriction therapy. Interviewing patients, he was told that the suffering patients experienced when implementing sleep restriction subsided within a couple of weeks, and that the craving they developed for sleep led to sleep that was deeper and more efficient.61 Conducting objective measures of sleep restriction therapy, Dr. Kyle found that although sleep efficiency improved within four weeks, daytime attention and reaction speed deteriorated, not returning to starting values until after three months of the therapy.62
Sleep Loss and Sex Hormones
Fiona Baker, PhD, (Senior Program Director, Human Sleep Research, SRI International, Menlo Park, California) studies sleep disturbances associated with menstruation and menopause. Hot flashes refer to episodes of sweating followed by chills.63 Hot flashes are reported for 12.5% of women just before menopause, 79.0% during menopause, and 50.7% following menopause. Chronic insomnia increases with increased severity of hot flashes.64 Dr. Baker found that heart rate increased when hot flashes occurred.65 Dr. Baker studied young women (average age 21) who did not have menstrual complaints, and found reduced sleep quality for three days before menstruation and for four days during menstruation.66
Katherine Sharkey, MD, PhD, (Internist, Rhode Island Hospital, West Warwick, Rhode Island) studies the effects of aging and hormonal changes on sleep. In men between the ages of 64 and 74 the time by which nighttime sleep is reduced corresponded with the amount by which testosterone is reduced.67 In women, menstrual irregularities begin at an average age of 46, lasting two to eight years.68 Dr. Sharkey has shown that the greater incidence of waking during sleep is associated with higher levels of progesterone near the time of menstruation.69
Sleep Disturbance with Shift Work
Karl Doghramji, MD, (Director, Sleep Disorder Center, Jefferson University Hospitals, Philadelphia, Pennsylvania) reported on the health consequences of shift work. Worldwide, about 20% of the labor force works outside the hours of 7 A.M. to 6 P.M.70 Shift workers suffer more obesity, cardiovascular disease, and cancer as well as experiencing nearly triple the incidence of occupational accidents as day workers.70 Industrial productivity has been found to be about 5% lower during night shifts.71 Caffeine and naps could reduce the accident rate and increase productivity.
A study in Japan found that prostate cancer among rotating-shift workers was triple normal, but that fixed-shift night workers had a regular prostate cancer incidence.72 The authors speculated that disruption of the circadian rhythm of melatonin secretion was responsible. A study of American nurses found that rotating-shift work was associated with a 4% increase in ischemic stroke for every five years worked.73 These authors also speculated that disruption of the circadian rhythm of melatonin secretion could be responsible.
A study of Iranian long-distance night-shift drivers found an increased incidence of metabolic syndrome.74 In this case, the authors speculated that physical inactivity and roadside restaurant food was responsible. But healthy adults subjected to three weeks of combined sleep restriction (5-6 hours sleep per 24 hours) and circadian disruption (28 hour “days” in a laboratory setting) showed a 32% decrease in insulin secretion after a standardized meal. Elevated blood glucose rose to prediabetic levels in some cases. The subjects showed an 8% drop in resting metabolic rate, which would result in a weight gain of approximately 12.5 pounds per year.75
Obstructive Sleep Apnea (OSA)
Ina Djonlagic, MD, (Instructor, Harvard Medical School, Boston, Massachusetts) has studied the effects of obstructive sleep apnea (OSA). Persons with obstructive sleep apnea suffer bouts of halted breathing (apnea) lasting 20 to 40 seconds several times per hour during sleep, resulting in disrupted sleep quality. Victims are often unaware of their condition, although they experience excessive daytime sleepiness.76,77 Obstructive sleep apnea victims typically have elevated blood pressure, and a four-fold increase in heartbeat irregularities in the atrium of the heart. 78 For people without obstructive sleep apnea, sudden cardiac death risk is minimal between midnight and 6 A.M., but for obstructive sleep apnea victims the risk of sudden cardiac death during that time is elevated more than two-and-a-half times.79 Up to 95% of patients with obstructive sleep apnea snore.76 Obstructive sleep apnea is twice as common in men as it is in women.80 Other risk factors include being overweight, being over age 40, and having an enlarged neck, tongue, or tonsils. Alcohol and other sedatives contribute to obstructive sleep apnea by relaxing throat muscles. Dr. Djonlagic has found that untreated obstructive sleep apnea caused cognitive deficits and increases the likelihood of becoming demented.81 Sleeping on one’s back greatly increases the risk of obstructive sleep apnea, whereas sleeping on the side reduces it. 82 Sleeping with an appliance that keeps the airways open with continuous positive airway pressure (CPAP) is the “gold standard” treatment for obstructive sleep apnea.83 CPAP reduces the risk of cardiovascular death.84 Dr. Djonlagic has found immediate benefits for attention, vigilance, and well-being after the first night of CPAP in obstructive sleep apnea patients.85
Sleep Disorders in Soldiers
Vincent Mysliwiec, MD, (Internist, Madigan Army Medical Center, Tacoma, Washington) has studied the sleep disturbances of soldiers returning from combat. Soldiers on deployment often sleep at odd hours, disrupting circadian rhythm.86 According to one report, sleep time for soldiers averages 6.5 hours, but soldiers suffering from post-traumatic stress disorder (PTSD) sleep significantly less.86 In the military, there is a stigma associated with mental health problems, which may account for the fact that soldiers are about five times more likely to seek help for insomnia than for a mental health problem.87 About one quarter of soldiers deployed to combat stations during the war on terror have experienced traumatic brain injury (TBI) from improvised explosive devices.88 Compared to soldiers without traumatic brain injury, soldiers with a single traumatic brain injury had about four times the incidence of insomnia, whereas soldiers with multiple traumatic brain injuries had close to ten times the incidence of insomnia.89 Soldiers with traumatic brain injury from blast injuries were more likely to develop anxiety and insomnia, whereas blunt trauma more often resulted in obstructive sleep apnea.90
Age, Cognitive Ability, and Sleep
Anne Richards, MD, (Assistant Professor, University of California School of Medicine, San Francisco, California) used data from the online cognitive training program Lumosity to assess the relationship between age, cognitive ability, and reported sleep time. Other studies have indicated that consolidation of learning occurs during sleep for young adults, but not for healthy elderly adults,91 and that those who sleep between 6 and 9 hours per night do better on cognitive tests than those who sleep more or less.92 Dr. Richards found that for young Lumosity participants, cognitive scores were highest for those reporting 7 hours of sleep per night. But, unexpectedly, for the oldest participants, those sleeping 7 hours per night had worse scores than those sleeping more or less.93
Sleep and the Circadian Rhythm
Derk-Jan Dijk, PhD, (Professor of Sleep and Physiology, University of Surrey, Surrey, England) has been studying the effects of the day-night circadian rhythm on sleep and health.94 The circadian rhythm is characterized by melatonin release in the evening (which promotes sleep) and cortisol release before awakening (which promotes arousal).15 Dr. Dijk has shown that the efficiency of sleep for replenishment of brain function for humans is highest when sleep times coincide with the 24-hour circadian rhythm, and is greatly reduced when circadian rhythm is disrupted by being in a sleep laboratory with an artificial 28-hour day.95 He has also shown that the human “circadian clock” is disrupted by insufficient sleep.96 Dr. Dijk has reported that the study of three geographically-separated modern hunter-gatherer communities without access to electric lighting showed an average sleep time of 7.7 hours, estimated to be about a half-hour longer than in modern industrial society.97 Comparing three modern industrial countries (Singapore, Norway, and the United Kingdom) he found no seasonal variation in sleep time between the three countries, despite the fact that two of the countries are at high latitude and Singapore is near the equator (lacking much seasonal variation).98
With many sessions at the conference running in parallel, I may have missed presentations about two important sleep problems which I will now mention.
A study in Europe found that more than 5% of the population suffered from restless legs syndrome (more often women than men), which causes insomnia.99 This affliction is largely inherited, and is characterized by uncomfortable leg sensations when at rest, causing victims to move their legs to stop the discomfort.100
The urge to urinate at night is a frequent source of sleep disturbance. Although roughly 10% of those between age 20 and 40 urinate at least twice per night, nearly half of women and more than two-thirds of men over age 70 urinate at least twice per night.101 Treatment of benign prostatic hyperplasia (BPH) in men only has a mild benefit.102 Drug treatments include antidepressants, diuretics,103 and drugs like finasteride that shrink enlarged prostate glands104 as well as tamsulosin (Flomax®) that facilitate more complete emptying of the bladder.105 Patients are advised to avoid drinking too many liquids at night.103
Concerning the conference, it seems that most people would be healthier if they would get more sleep. Apparently, modern life increasingly tempts people to stay awake longer so as to be more productive or more entertained. Melatonin and the omega-3 fatty acid DHA may help some people to sleep better, but clearly more is needed to address this widespread problem.
A major problem with sleep research is that it too often relies on people reporting on their sleep rather than objective data. Laboratory measures of sleep (polysomnography) are often at variance with subjective experience. And sleeping in a laboratory can disrupt sleep. Based on the presentations I heard, I could imagine many of the consequences of poor sleep: inflammation, liver DNA damage, blood pressure, or insulin resistance; blood cortisol or immune function; poor performance on standardized tests for cognition and reaction time. “Personalized medicine” has not yet arrived in sleep research because only averages of results for many people are used. The variation in sleep-need from one individual to another might be very large.106
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- Herculano-Houzel S. Sleep it out. Science. 2013;342(6156):316-7.
- Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373-7.
- Lee H, Xie L, Yu M, et al. The effect of body posture on brain glymphatic transport. J Neurosci. 2015;35(31):11034-44.
- Huang Y, Potter R, Sigurdson W, et al. Effects of age and amyloid deposition on Abeta dynamics in the human central nervous system. Arch Neurol. 2012;69(1):51-8.
- Mackiewicz M, Shockley KR, Romer MA, et al. Macromolecule biosynthesis: a key function of sleep. Physiol Genomics. 2007;31(3):441-57.
- Stickgold R, Walker MP. Memory consolidation and reconsolidation: what is the role of sleep? Trends Neurosci. 2005;28(8):408-15.
- Rauchs G, Desgranges B, Foret J, et al. The relationships between memory systems and sleep stages. J Sleep Res. 2005;14(2):123-40.
- Raichle ME, Gusnard DA. Appraising the brain’s energy budget. Proc Nat Acad Sci USA. 2002;99(16):10237-9.
- Reichert CF, Maire M, Schmidt C, et al. Sleep-wake regulation and its impact on working memory performance: the role of adenosine. Biology (Basel). 2016;5(1).
- Snel J, Lorist MM. Effects of caffeine on sleep and cognition. Prog Brain Res. 2011;190:105-17.
- Mednick SC, Cai DJ, Kanady J, et al. Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory. Behav Brain Res. 2008;193(1):79-86.
- Ferrara M, De Gennaro L. How much sleep do we need? Sleep Med Rev. 2001;5(2):155-79.
- Foley DJ, Monjan A, Simonsick EM, et al. Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6,800 persons over three years. Sleep. 1999;22 Suppl 2:S366-72.
- Duffy JF, Willson HJ, Wang W, et al. Healthy older adults better tolerate sleep deprivation than young adults. J Am Geriatr Soc. 2009;57(7):1245-51.
- Adan A, Archer SN, Hidalgo MP, et al. Circadian typology: a comprehensive review. Chronobiol Int. 2012;29(9):1153-75.
- Vgontzas AN, Liao D, Pejovic S, et al. Insomnia with short sleep duration and mortality: the Penn State cohort. Sleep. 2010;33(9):1159-64.
- Van Dongen HP, Maislin G, Mullington JM, et al. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003;26(2):117-26.
- Weber M, Webb CA, Deldonno SR, et al. Habitual ‘sleep credit’ is associated with greater grey matter volume of the medial prefrontal cortex, higher emotional intelligence and better mental health. J Sleep Res. 2013;22(5):527-34.
- Stamatakis KA, Punjabi NM. Long sleep duration: a risk to health or a marker of risk? Sleep Med Rev. 2007;11(5):337-9.
- Hale L, Parente V, Dowd JB, et al. Fibrinogen may mediate the association between long sleep duration and coronary heart disease. J Sleep Res. 2013;22(3):305-14.
- Brooks A, Lack L. A brief afternoon nap following nocturnal sleep restriction: which nap duration is most recuperative? Sleep. 2006;29(6):831-40.
- Montgomery P, Burton JR, Sewell RP, et al. Fatty acids and sleep in UK children: subjective and pilot objective sleep results from the DOLAB study--a randomized controlled trial. J Sleep Res. 2014;23(4):364-88.
- Ford ES, Cunningham TJ, Croft JB. Trends in self-reported sleep duration among US adults from 1985 to 2012. Sleep. 2015;38(5):829-32.
- Ford ES, Cunningham TJ, Giles WH, et al. Trends in insomnia and excessive daytime sleepiness among U.S. adults from 2002 to 2012. Sleep Med. 2015;16(3):372-8.
- Basner M, McGuire S, Goel N, et al. A new likelihood ratio metric for the psychomotor vigilance test and its sensitivity to sleep loss. J Sleep Res. 2015;24(6):702-13.
- Spaeth AM, Dinges DF, Goel N. Phenotypic vulnerability of energy balance responses to sleep loss in healthy adults. Sci Rep. 2015;5:14920.
- Killick R, Banks S, Liu PY. Implications of sleep restriction and recovery on metabolic outcomes. J Clin Endocrinol Metab. 2012;97(11):3876-90.
- Spiegel K, Tasali E, Penev P, et al. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004;141(11):846-50.
- Banks S, Van Dongen HP, Maislin G, et al. Neurobehavioral dynamics following chronic sleep restriction: dose-response effects of one night for recovery. Sleep. 2010;33(8):1013-26.
- Leproult R, Van Cauter E. Role of sleep and sleep loss in hormonal release and metabolism. Endocr Dev. 2010;17:11-21.
- Cappuccio FP, D’Elia L, Strazzullo P, et al. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2010;33(2):414-20.
- Leproult R, Holmback U, Van Cauter E. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes. 2014;63(6):1860-9.
- Waterhouse J, Reilly T, Atkinson G, et al. Jet lag: trends and coping strategies. Lancet. 2007;369(9567):1117-29.
- Leproult R, Deliens G, Gilson M, et al. Beneficial impact of sleep extension on fasting insulin sensitivity in adults with habitual sleep restriction. Sleep. 2015;38(5):707-15.
- Everson CA. Clinical assessment of blood leukocytes, serum cytokines, and serum immunoglobulins as responses to sleep deprivation in laboratory rats. Am J Physiol Regul Integr Comp Physiol. 2005;289(4):R1054-63.
- Everson CA, Toth LA. Systemic bacterial invasion induced by sleep deprivation. Am J Physiol Regul Integr Comp Physiol. 2000;278(4):R905-16.
- Cohen S, Doyle WJ, Alper CM, et al. Sleep habits and susceptibility to the common cold. Arch Intern Med. 2009;169(1):62-7.
- Everson CA, Szabo A. Repeated exposure to severely limited sleep results in distinctive and persistent physiological imbalances in rats. PLoS One. 2011;6(8):e22987.
- Everson CA, Henchen CJ, Szabo A, et al. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats. Sleep. 2014;37(12):1929-40.
- Jackson ML, Gunzelmann G, Whitney P, et al. Deconstructing and reconstructing cognitive performance in sleep deprivation. Sleep Med Rev. 2013;17(3):215-25.
- Whitney P, Hinson JM, Jackson ML, et al. Feedback blunting: total sleep deprivation impairs decision making that requires updating based on feedback. Sleep. 2015;38(5):745-54.
- Tucker AM, Whitney P, Belenky G, et al. Effects of sleep deprivation on dissociated components of executive functioning. Sleep. 2010;33(1):47-57.
- Satterfield BC, Wisor JP, Field SA, et al. TNFalpha G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults. Brain Behav Immun. 2015;47:66-74.
- Mullington JM, Simpson NS, Meier-Ewert HK, et al. Sleep loss and inflammation. Best Pract Res Clin Endocrinol Metab. 2010;24(5):775-84.
- Imeri L, Opp MR. How (and why) the immune system makes us sleep. Nat Rev Neurosci. 2009;10(3):199-210.
- Vgontzas AN, Fernandez-Mendoza J, Liao D, et al. Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev. 2013;17(4):241-54.
- Fernandez-Mendoza J, Vgontzas AN, Calhoun SL, et al. Insomnia symptoms, objective sleep duration and hypothalamic-pituitary-adrenal activity in children. Eur J Clin Invest. 2014;44(5):493-500.
- Fernandez-Mendoza J, Shea S, Vgontzas AN, et al. Insomnia and incident depression: role of objective sleep duration and natural history. J Sleep Res. 2015;24(4):390-8.
- Fernandez-Mendoza J, Vgontzas AN, Kritikou I, et al. Natural history of excessive daytime sleepiness: role of obesity, weight loss, depression, and sleep propensity. Sleep. 2015;38(3):351-60.
- Riemann D, Spiegelhalder K, Feige B, et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010;14(1):19-31.
- Riemann D, Nissen C, Palagini L, et al. The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol. 2015;14(5):547-58.
- Basta M, Chrousos GP, Vela-Bueno A, et al. Chronic insomnia and stress system. Sleep Med Clin. 2007;2(2):279-91.
- Spiegelhalder K, Riemann D. Losing sleep. Lancet Neurol. 2015;14(6):571.
- Hertenstein E, Nissen C, Riemann D, et al. The exploratory power of sleep effort, dysfunctional beliefs and arousal for insomnia severity and polysomnography-determined sleep. J Sleep Res. 2015;24(4):399-406.
- Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry. 2004;65 Suppl 5:7-12.
- Ebrahim IO, Shapiro CM, Williams AJ, et al. Alcohol and sleep I: effects on normal sleep. Alcohol Clin Exp Res. 2013;37(4):539-49.
- Oswald I. Sleep, dreaming and drugs. Proc R Soc Med. 1969;62(2):151-3.
- Lemoine P, Nir T, Laudon M, et al. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16(4):372-80.
- Luthringer R, Muzet M, Zisapel N, et al. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009;24(5):239-49.
- Kyle SD, Aquino MR, Miller CB, et al. Towards standardisation and improved understanding of sleep restriction therapy for insomnia disorder: A systematic examination of CBT-I trial content. Sleep Med Rev. 2015;23:83-8.
- Kyle SD, Morgan K, Spiegelhalder K, et al. No pain, no gain: an exploratory within-subjects mixed-methods evaluation of the patient experience of sleep restriction therapy (SRT) for insomnia. Sleep Med. 2011;12(8):735-47.
- Kyle SD, Miller CB, Rogers Z, et al. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. Sleep. 2014;37(2):229-37.
- Nelson HD. Menopause. Lancet. 2008;371(9614):760-70.
- Ohayon MM. Severe hot flashes are associated with chronic insomnia. Arch Intern Med. 2006;166(12):1262-8.
- de Zambotti M, Colrain IM, Sassoon SA, et al. Vagal withdrawal during hot flashes occurring in undisturbed sleep. Menopause. 2013;20(11):1147-53.
- Baker FC, Driver HS. Self-reported sleep across the menstrual cycle in young, healthy women. J Psychosom Res. 2004;56(2):239-43.
- Penev PD. Association between sleep and morning testosterone levels in older men. Sleep. 2007;30(4):427-32.
- Lord C, Sekerovic Z, Carrier J. Sleep regulation and sex hormones exposure in men and women across adulthood. Pathol Biol (Paris). 2014;62(5):302-10.
- Sharkey KM, Crawford SL, Kim S, et al. Objective sleep interruption and reproductive hormone dynamics in the menstrual cycle. Sleep Med. 2014;15(6):688-93.
- Wright KP, Jr., Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Med Rev. 2013;17(1):41-54.
- Folkard S, Tucker P. Shift work, safety and productivity. Occup Med (Lond). 2003;53(2):95-101.
- Kubo T, Ozasa K, Mikami K, et al. Prospective cohort study of the risk of prostate cancer among rotating-shift workers: findings from the Japan collaborative cohort study. Am J Epidemiol. 2006;164(6):549-55.
- Brown DL, Feskanich D, Sanchez BN, et al. Rotating night shift work and the risk of ischemic stroke. Am J Epidemiol. 2009;169(11):1370-7.
- Mohebbi I, Shateri K, Seyedmohammadzad M. The relationship between working schedule patterns and the markers of the metabolic syndrome: comparison of shift workers with day workers. Int J Occup Med Environ Health. 2012;25(4):383-91.
- Buxton OM, Cain SW, O’Connor SP, et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012;4(129):129ra43.
- Azagra-Calero E, Espinar-Escalona E, Barrera-Mora JM, et al. Obstructive sleep apnea syndrome (OSAS). Review of the literature. Med Oral Patol Oral Cir Bucal. 2012;17(6):e925-9.
- Torelli F, Moscufo N, Garreffa G, et al. Cognitive profile and brain morphological changes in obstructive sleep apnea. Neuroimage. 2011;54(2):787-93.
- Floras JS. Sleep apnea and cardiovascular risk. J Cardiol. 2014;63(1):3-8.
- Gami AS, Howard DE, Olson EJ, et al. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005;352(12):1206-14.
- Morris LG, Kleinberger A, Lee KC, et al. Rapid risk stratification for obstructive sleep apnea, based on snoring severity and body mass index. Otolaryngol Head Neck Surg. 2008;139(5):615-8.
- Djonlagic I, Guo M, Matteis P, et al. Untreated sleep-disordered breathing: links to aging-related decline in sleep-dependent memory consolidation. PLoS One. 2014;9(1):e85918.
- Menon A, Kumar M. Influence of body position on severity of obstructive sleep apnea: a systematic review. ISRN Otolaryngol. 2013;2013:670381.
- Spicuzza L, Caruso D, Di Maria G. Obstructive sleep apnoea syndrome and its management. Ther Adv Chronic Dis. 2015;6(5):273-85.
- Ludka O, Konecny T, Somers V. Sleep apnea, cardiac arrhythmias, and sudden death. Tex Heart Inst J. 2011;38(4):340-3.
- Djonlagic I, Guo M, Matteis P, et al. First night of CPAP: impact on memory consolidation attention and subjective experience. Sleep Med. 2015;16(6):697-702.
- Luxton DD, Greenburg D, Ryan J, et al. Prevalence and impact of short sleep duration in redeployed OIF soldiers. Sleep. 2011;34(9):1189-95.
- Livingston WS, Rusch HL, Nersesian PV, et al. Improved Sleep in Military Personnel is Associated with Changes in the Expression of Inflammatory Genes and Improvement in Depression Symptoms. Front Psychiatry. 2015;6:59.
- Heinzelmann M, Reddy SY, French LM, et al. Military personnel with chronic symptoms following blast traumatic brain injury have differential expression of neuronal recovery and epidermal growth factor receptor genes. Front Neurol. 2014;5:198.
- Bryan CJ. Repetitive traumatic brain injury (or concussion) increases severity of sleep disturbance among deployed military personnel. Sleep. 2013;36(6):941-6.
- Collen J, Orr N, Lettieri CJ, et al. Sleep disturbances among soldiers with combat-related traumatic brain injury. Chest. 2012;142(3):622-30.
- Scullin MK, Bliwise DL. Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research. Perspect Psychol Sci. 2015;10(1):97-137.
- Gildner TE, Liebert MA, Kowal P, et al. Associations between sleep duration, sleep quality, and cognitive test performance among older adults from six middle income countries: results from the Study on Global Ageing and Adult Health (SAGE). J Clin Sleep Med. 2014;10(6):613-21.
- Available at: http://www.neurologyreviews.com/specialty-focus/sleep/article/how-much-sleep-is-required-for-peak-cognitive-performance/fed5d4521ed235985885ea521d11ecee.html. Accessed April 29, 2016.
- Laing EE, Johnston JD, Moller-Levet CS, et al. Exploiting human and mouse transcriptomic data: Identification of circadian genes and pathways influencing health. Bioessays. 2015;37(5):544-56.
- Lazar AS, Lazar ZI, Dijk DJ. Circadian regulation of slow waves in human sleep: Topographical aspects. Neuroimage. 2015;116:123-34.
- Archer SN, Laing EE, Moller-Levet CS, et al. Mistimed sleep disrupts circadian regulation of the human transcriptome. Proc Natl Acad Sci U S A. 2014;111(6):E682-91.
- Dijk DJ, Skeldon AC. Biological rhythms: Human sleep before the industrial era. Nature. 2015;527(7577):176-7.
- Lo JC, Leong RL, Loh KK, et al. Young Adults’ Sleep Duration on Work Days: Differences between East and West. Front Neurol. 2014;5:81.
- Ohayon MM, Roth T. Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. J Psychosom Res. 2002;53(1):547-54.
- Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med. 2009;266(5):419-31.
- Bosch JL, Weiss JP. The prevalence and causes of nocturia. J Urol. 2013;189(1 Suppl):S86-92.
- Yoshimura K. Correlates for nocturia: a review of epidemiological studies. Int J Urol. 2012;19(4):317-29.
- Yazici CM, Kurt O. Combination therapies for the management of nocturia and its comorbidities. Res Rep Urol. 2015;7:57-63.
- Tacklind J, Fink HA, Macdonald R, et al. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2010(10):Cd006015.
- Fusco F, Palmieri A, Ficarra V, et al. Alpha1-blockers improve benign prostatic obstruction in men with lower urinary tract symptoms: A systematic review and meta-analysis of urodynamic studies. Eur Urol. 2016.
- Blunden S, Galland B. The complexities of defining optimal sleep: empirical and theoretical considerations with a special emphasis on children. Sleep Med Rev. 2014;18(5):371-8.