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Sleep: A Health Priority Phyllis C. Zee, MD, Ph. D Benjamin and Virginia T. Sleep: A Health Priority Phyllis C. Zee, MD, Ph. D Benjamin and Virginia T. Boshes Professor of Neurology Director Center for Circadian and Sleep Medicine Northwestern University Feinberg School of Medicine Director Northwestern Medicine Sleep Disorders Center

Sleep and Circadian Rhythm: Critical for Health, Learning and Safety – – – Cognition Sleep and Circadian Rhythm: Critical for Health, Learning and Safety – – – Cognition and learning Physical performance Mental health Physical health Safety

Hand-Eye Coordination Performance Sleep Loss and Motor Performance Driving Under the Influence Reid and Hand-Eye Coordination Performance Sleep Loss and Motor Performance Driving Under the Influence Reid and Dawson, Nature, 1997

Sleep Improves Memory Motor Skill Task SLEEP 4 -1 -3 -2 -4 Repeat 30 Sleep Improves Memory Motor Skill Task SLEEP 4 -1 -3 -2 -4 Repeat 30 sec 12 trials Train at 10 am: 14/trial to 22/trial Wake Sequences/trial 28 26 24 22 Test at 10 pm Sleep Test at 10 am (following day) 10 am (Day 1) 10 pm 10 am (Day 1) (Day 2) Walker & Stickgold, 2004 Neuron

The “Brainwashing” Function of Sleep Neurodegenerative Disease Alzheimer’s Parkinson’s Traumatic Brain Injury Neurotoxins Disrupted The “Brainwashing” Function of Sleep Neurodegenerative Disease Alzheimer’s Parkinson’s Traumatic Brain Injury Neurotoxins Disrupted Sleep References Schlosser Covell et al. 2012 Aziz et al. 2009 Morton et al. 2005, Pallier, et al. 2007 Boone et al. 2012 Mathias, Alvaro 2012

The “Brainwashing” Function of Sleep Neurodegenerative Disease Alzheimer’s Parkinson’s Traumatic Brain Injury Neurotoxins Disrupted The “Brainwashing” Function of Sleep Neurodegenerative Disease Alzheimer’s Parkinson’s Traumatic Brain Injury Neurotoxins Disrupted Sleep Xie et al 2013 Science References Schlosser Covell et al. 2012 Aziz et al. 2009 Morton et al. 2005, Pallier, et al. 2007 Boone et al. 2012 Mathias, Alvaro 2012

The “Brainwashing” Function of Sleep Psychiatric Disease Depression Schizophrenia Disrupted Sleep Xie et al The “Brainwashing” Function of Sleep Psychiatric Disease Depression Schizophrenia Disrupted Sleep Xie et al 2013 Science References Schlosser Covell et al. 2012 Aziz et al. 2009 Morton et al. 2005, Pallier, et al. 2007 Boone et al. 2012 Mathias, Alvaro 2012

Why is Sleep Health a Priority? w 25 -30% of the population in industrialized Why is Sleep Health a Priority? w 25 -30% of the population in industrialized countries have a chronic sleep disorder w w 35% get less than 6 hours of sleep per day w Sleep disorders and deprivation are associated with many deleterious health consequences 28% of adults report frequent insufficient sleep 5% report falling asleep driving in the past 30 days Annual direct (medical) and indirect (accidents, lost productivity, etc) costs total hundreds of billions of dollars

Relationship Between Sleep and Health “Recent research links lack of sleep to health problems, Relationship Between Sleep and Health “Recent research links lack of sleep to health problems, such as obesity, diabetes and cardiovascular disease. ” US News & World Report, October 2000 “Sleep and Health: Everywhere and in Both Directions” Zee PC, et al. Arch Intern Med. 2006; 166: 1686 -1688.

Mechanism Linking Sleep and Health w In the laboratory setting, short-term sleep restriction leads Mechanism Linking Sleep and Health w In the laboratory setting, short-term sleep restriction leads to a variety of adverse physiologic sequelae, including – Impaired glucose control – Increased cortisol – Increased blood pressure – Sympathetic activation – Increased markers of inflammation – Changes in appetite hormones (leptin) w These data suggest that chronic sleep restriction may have long-term health consequences Zee PC, et al. Arch Intern Med. 2006; 166: 1686 -1688.

Sleep Duration and Body Mass Index Wisconsin Sleep Cohort Study Adjusted Body Mass Index Sleep Duration and Body Mass Index Wisconsin Sleep Cohort Study Adjusted Body Mass Index 33 32 (230) 31 (507) (347) (121) (623) 30 6 7 8 Average nightly sleep (hours) Taheri S, et al. PLo. S Med. 2004; 1: e 62. 9

Adiposity and Sleep Duration in Children Adolescents are not getting enough sleep: risk for Adiposity and Sleep Duration in Children Adolescents are not getting enough sleep: risk for future poor health social/economic burden for the world 23 17 (N=500) 20 17 14 Sleep Duration: < 8 hrs 8 -9 hrs ≥ 9 hrs 11 12 13 14 15 16 17 18 19 20 Age (years) in females Yu Y, et al. Zee. Sleep. 2007; 30: 1688 -1697. Total Fat, kg BMI/ kg/m 2 15 13 11 9 Sleep Duration: < 8 hrs 8 -9 hrs ≥ 9 hrs 7 5 11 12 13 14 15 16 17 18 19 Age (years) in females 20

Age-Adjusted Relative Risks of Incident Coronary Heart Disease and Diabetes (Nurses’ Health Study) Coronary Age-Adjusted Relative Risks of Incident Coronary Heart Disease and Diabetes (Nurses’ Health Study) Coronary artery disease • 2 • 1. 5 • 1. 0 • 1 • 0. 5 • 0. 0 Relative Risk • 2. 0 Diabetes • 0 • 5 • 6 • 7 • 8 • 9+ • 5 • 6 • 7 • 8 Reported Sleep Duration (hours) Ayas NT, et al. Arch Intern Med. 2003; 163: 205 -209. Ayas NT, et al. Diabetes Care. 2003; 26: 380 -384. • 9+

SLEEP QUALITY and HEALTH RISK Research from many countries show a u-shaped function of SLEEP QUALITY and HEALTH RISK Research from many countries show a u-shaped function of Poor sleep quality are health risks relative to sleep associated with increased risk duration of: High risk Low risk Hours of sleep per night Hypertension Obesity Diabetes Stroke Myocardial infarction Coronary disease Colorectal adenoma Mortality

Sleep and Sleep Disorders Affects Many Aspects of Physical and Mental Health Muscle Insulin Sleep and Sleep Disorders Affects Many Aspects of Physical and Mental Health Muscle Insulin resistance DIABETES Liver Insulin resistance Pancreas Abnormal insulin Brain Cogniition and mood stroke Inflammation -Breast -Prostate Sleep Deficiency Adipose Obesity Heart, Vessel, Endothelium GI tract Peptic ulcer CRSD, circadian rhythm sleep disorder. Klerman EB. J Biol Rhythms. 2005; 20(4): 375 -386; Young ME, Bray MS. Sleep Med. 2007; 8(6): 656 -667. Cancer Cardiovascular disease Kidney Nocturia

Causes of Sleep Deficiency Insufficient Sleep (behavioral/ psychosocial factors) Sleep Disorders (50 -70 million) Causes of Sleep Deficiency Insufficient Sleep (behavioral/ psychosocial factors) Sleep Disorders (50 -70 million) - insomnia - sleep apnea - shift work - restless legs - narcolepsy Physical, cognitive, emotional, performance, safety impairments Circadian Rhythm Disruption delayed sleep phase Shift work Medical, Neurological Psychiatric Disorders

Prevalence of Insomnia Disorder Canada 10% Sweden 6% France 6% Italy 7% USA 10%-20% Prevalence of Insomnia Disorder Canada 10% Sweden 6% France 6% Italy 7% USA 10%-20% Finland 12% Belgium 9% Germany 6% Singapore 15% China 12% Japan 11% South Korea 5%

Poor Health Impacts Prevalence of Insomnia in Older Adult Population All Healthiest n = Poor Health Impacts Prevalence of Insomnia in Older Adult Population All Healthiest n = 9, 282; aged ≥ 65 years 60 Percent 50 40 30 20 10 0 Insomnia Any Chronic Complaint Foley DJ et al. Sleep. 1995; 18: 425 -432. GSA Webinar on Sleep Health and the Appropriate Use of OTC Sleep Aids in Older Adults

Impact of Insomnia on Quality of Life Physical Functioning Mental Health Role Physical Role Impact of Insomnia on Quality of Life Physical Functioning Mental Health Role Physical Role Emotional Social Functioning Bodily Pain General Health Mild Insomnia (n = 422) Axes represent subscales of the SF-36. All P values <. 05 (range. 000 -. 023). GSA National Summit on OTC Sleep Aids and Sleep Health in Older Adults

Days-Out-of-Role Associated With Insomnia and Comorbid Conditions in America Insomnia Survey Hajak G et Days-Out-of-Role Associated With Insomnia and Comorbid Conditions in America Insomnia Survey Hajak G et al. Biol Psychiatry. 2011; 70: 1063 -1073. GSA National Summit on OTC Sleep Aids and Sleep Health in Older Adults

Association of Hypertension with Insomnia and Objective Sleep Duration Poor sleep/5 -6 hrs Poor Association of Hypertension with Insomnia and Objective Sleep Duration Poor sleep/5 -6 hrs Poor sleep/ ≤ 5 hrs Insomnia/5 -6 hrs Insomnia/≤ 5 hrs 2. 4 (1. 4 -4. 3) 3. 5 (1. 6 -7. 9) 5. 1 (2. 2 -11. 8) Odds Ratio Vgontzas et al, SLEEP 2009

Association of Diabetes with Insomnia and Objective Sleep Duration Normal sleeping/< 5 hrs Poor Association of Diabetes with Insomnia and Objective Sleep Duration Normal sleeping/< 5 hrs Poor sleep/< 5 hrs Insomnia/5 -6 hrs Insomnia/< 5 hrs 3. 0 (1. 2 -7. 0) Odds Ratio Vgontzas et al, Diabetes Care 2009

Sleep Disordered Breathing (Obstructive Sleep Apnea) Repetitive episodes of partial or complete upper airway Sleep Disordered Breathing (Obstructive Sleep Apnea) Repetitive episodes of partial or complete upper airway obstruction during sleep, associated with hypoxemia, snoring, daytime sleepiness Common 2 -4% of children 4 to 9% of adults >20% of the elderly Even higher in African American, Asian and Hispanics source: Atlanta Institute for ENT

Sleep Apnea and Associated Conditions Hypoxemia Fragmented sleep Physical Inactivity Sleep Apnea Oxidative Stress Sleep Apnea and Associated Conditions Hypoxemia Fragmented sleep Physical Inactivity Sleep Apnea Oxidative Stress Glucose impairment Hypercoagulation Inflammation Obesity Diabetes Hypertension Heart Disease Stroke Cognitive impairment Depression

Global Problem: 24/7 Society and Shift Worke rs (1000 s ) % of Total Global Problem: 24/7 Society and Shift Worke rs (1000 s ) % of Total Force Production 2021 24. 4 Transportation & material moving 1900 28. 5 Food preparation & serving 1568 40. 4 Sales & related occupations 1464 15. 2 Office & administrative support 1458 9. 9 Health care practice & technical 1138 24. 6 Protection services 1125 50. 6 Management 612 6. 1 Cleaning & maintenance 609 17. 5 Personal care & service 542 28. 1 Health care support 534 28. 0 Installation, maintenance & repair 488 11. 4 Construction & extraction 256 4. 4 237 12. 7 221 14. 7 Starting Times for Full-Time Workers 26% of the U. S. Labor Force at Risk of SWD Top Occupations 12: 30 AM 10: 30 PM Elevated 25. 9% risk for SWD 2: 30 AM 1. 3% 0. 2% 8: 30 PM 0. 7% 0. 8% 1. 1% Start Time Varies 12. 2% 6: 30 PM 1. 0% 4: 30 PM 3. 1% 4: 30 AM 8. 6% 6: 30 AM 51. 5% 15. 6% 1. 2% 1. 1% 8: 30 AM 10: 30 AM 2: 30 PM 12: 30 PM Start time unknown: 1. 5% Day and 72. 6% evening workers 1. 5% Unknown risk Data source: Bureau of Labor Statistics (2004). Approximately 99. 8 million & social services Community workers >16 years. Arts, entertainment, media & http: //www. bls. gov/news. release/flex. t 05. htm. sports

Labor Force at Risk for Shift Work Disorder (SWD) 25. 9% 72. 6% Elevated Labor Force at Risk for Shift Work Disorder (SWD) 25. 9% 72. 6% Elevated risk for SWD Day and evening shift workers Unknown risk US Labor Force • Increase in glucose • Increase in insulin • Increase in mean arterial pressure • Increase cortisol before sleep time • Decreased inflammation Cardiovascular Obesity Diabetes Cognitive impairment Depression Gastrointestinal 1. 5% Stroke Cancer (breast, prostate) Source: Bureau of Labor Statistics, May 2004 data; available at http: //www. bls. gov/news. release/flex. t 07. htm.

Why Should Society Prioritize Sleep Health? School Learning Safety Mortality Physical Health Insufficient Disturbed Why Should Society Prioritize Sleep Health? School Learning Safety Mortality Physical Health Insufficient Disturbed Sleep Quality of Life Work Productivity Performance Mental Health Family Professional Relationships

Sleep is the 5 th Vital Sign Brief Questions for ALL: w w w Sleep is the 5 th Vital Sign Brief Questions for ALL: w w w Do you have problems falling asleep or staying asleep? Does sleep quality affect your mood or performance? Do you feel sleepy, drowsy, or tired during the day? Sleep Exercise Health Nutrition

Improving Sleep and Treatment of Sleep Disorders: Pathway to Better Health “Sleep is the Improving Sleep and Treatment of Sleep Disorders: Pathway to Better Health “Sleep is the golden chain that ties health and our bodies together” Behavioral state Mind-body function Neuroendocrine Cognition Fundamental mechanisms relevant to the entire organism Health and Disease

Improving Sleep: Immediate and Long Term Impact on Physical, Mental and Socioeconomic Health Bright Improving Sleep: Immediate and Long Term Impact on Physical, Mental and Socioeconomic Health Bright Light 1, 2, 3, 4 Sleep Hygiene Pharmacology CBT 1. Campbell SS et al. J Am Geriatr Soc. 1993; 41: 829 -836. 2. Murphy PJ and Campbell SS. J Sleep Res. 1996 Sep; 5(3): 165 -72. 3. Lack L, Wright H. Sleep. 1993; 16: 436 -443. 4. Ancoli-Israel et al. J Am Geriatr Soc. 2002 Feb; 50(2): 282 -9. Exercise 5 5. Naylor E et al. Sleep. 2000; 23: 87 -95.

Sleep Hygiene • Regular sleep-wake cycle • Regular morning/afternoon exercise • Increase daytime exposure Sleep Hygiene • Regular sleep-wake cycle • Regular morning/afternoon exercise • Increase daytime exposure to bright light • Avoid nighttime exposure to bright light • Avoid heavy meals or drinking within 3 hours of bedtime • Enhance sleep environment • Avoid caffeine, alcohol and nicotine • Relaxing routine • Warm bath/socks 1. Lippmann S, et al. South Med J. 2001; 94: 866 -873. 2. NHLBI Working Group on Insomnia. 1998. NIH Publication 98 -4088. 3. Kupfer DJ, Reynolds CF. N Engl J Med. 1997; 336: 341 -346.

Behavioral Therapy for Insomnia • Good sleep practices • Stay in bed only when Behavioral Therapy for Insomnia • Good sleep practices • Stay in bed only when asleep • Go to bed only when sleepy • Restrict time in bed • Establish regular wake up time • Exercise? Germain A, et al. J Clin Sleep Med. 2006; 2: 403– 406. Sleep Wake Circadian Wake

Effect of Daily Social and Physical Activity (Twice daily for 2 weeks) Community dwelling Effect of Daily Social and Physical Activity (Twice daily for 2 weeks) Community dwelling healthy elderly Increased slow wave sleep Improved daytime neuropsychological performance Naylor et al. , Sleep 23: 1, 2000

Exercise: Interventions for Chronic Insomnia • Age 55 and older with diagnosis of insomnia Exercise: Interventions for Chronic Insomnia • Age 55 and older with diagnosis of insomnia • No primary sleep pathology other than insomnia • No cognitive impairment (MMSE < 25)

Sleep Quality (PSQI) Epworth Sleepiness Scale * * * = P < 0. 05 Sleep Quality (PSQI) Epworth Sleepiness Scale * * * = P < 0. 05 Reid K et al Sleep Medicine, 2010 Exercise + Sleep Hygiene Alone

Quality of Life (SF-36) SF-36 Quality of Life Measures * * * Reid K Quality of Life (SF-36) SF-36 Quality of Life Measures * * * Reid K et al, Sleep Medicine, 2010

Treatment of Insomnia: Summary and Recommendations Identify sleep disorders, poor sleep hygiene, medications, sleep Treatment of Insomnia: Summary and Recommendations Identify sleep disorders, poor sleep hygiene, medications, sleep environment • Consider: – Regularity of wake-up time – Exposure to bright light and exercise – Noise and temperature of sleep environment • Restrict time in bed: Don’t stay in bed unless sleeping First line: Behavioral approaches before, or in combination with hypnotic medications

"That we are not much sicker and much madder than we are is due exclusively to that most blessed and blessing of all natural graces, sleep. ” A. Huxley