9/14/20 1 Sleep Matters Initiative Impact of Sleep Deficiency and Sleep Disorders on Health and Performance Stuart F. Quan, M.D.* Senior Physician and Clinical Director, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham Health McGinnis Professor of Sleep Medicine, Editor, Sleep and Health Education Program, Division of Sleep Medicine, Harvard Medical School *Dr. Quan is/was a paid consultant to Jazz Pharmaceuticals and Best Doctors; receives research/education support from Mary Ann & Stanley Snider via Combined Jewish Philanthropies, American Academy of Sleep Medicine and the National Institutes of Health; serves as the incumbent of a professorship endowed by Philips Respironics. Dr. Quan’s interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. USS Carl Vinson 1 Sleep Deficiency Epidemic • Nearly 1/3 of Americans sleep ≤6 hours/night, double the rate from 50 years ago • 69% of Americans report regularly getting insufficient sleep • 50-70 million Americans suffer from chronic sleep disorders • Every month, 56 million Americans admit struggling to keep their eyes open while driving and 8 million fall asleep at the wheel monthly • 500,000 driving injuries and 55,000 debilitating related injuries occur annually due to fatigue • 6,400 sleep-related fatalities occur annually 20% of serious & fatal crash injuries SLEEP MATTERS INITIATIVE Brigham Health Boston, MA 2 Physician Work Hours, Health, and Patient Safety 3 Percentage of short sleepers (<7h) in the U.S. population From 1965 to 1999 Physician Work Hours, Health, and Patient Safety Populations at higher risk for diabetes Whites African- Americans Hispanics Other 0% 10% 20% 30% 40% 50% 60% 4 24 hours of wakefulness induces performance impairment comparable with blood alcohol concentration 0.10% 5 Characteristics of Sleep • Ubiquitous: All animals (e.g., mammals, insects) • Obligatory: Animals die if deprived of sleep long enough • Complex: REM sleep and non-REM sleep • Homeostatically regulated: Amount and content of sleep depends on prior wake duration (including naps, extended wake) • If insufficient, waking, performance, alertness, and errors and accidents affected • Sleep Disorders exist: Associated with other disorders, including cardiovascular disease 6
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9/14/20
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Sleep Matters InitiativeImpact of Sleep Deficiency and Sleep Disorders on Health and Performance
Stuart F. Quan, M.D.* Senior Physician and Clinical Director, Division of Sleep and
Circadian Disorders, Departments of Medicine and Neurology, Brigham Health
McGinnis Professor of Sleep Medicine, Editor, Sleep and Health Education Program, Division of Sleep Medicine,
Harvard Medical School
*Dr. Quan is/was a paid consultant to Jazz Pharmaceuticals and Best Doctors; receives research/education support from Mary Ann & Stanley Snider via Combined Jewish Philanthropies, American Academy of Sleep Medicine and the National Institutes of Health; serves as the incumbent of a professorship endowed by Philips Respironics. Dr. Quan’s interests were reviewed and are managed by Brigham and Women’s Hospital and
Partners HealthCare in accordance with their conflict of interest policies.
USS CarlVinson
1
Sleep Deficiency Epidemic• Nearly 1/3 of Americans sleep ≤6 hours/night,
double the rate from 50 years ago• 69% of Americans report regularly getting
insufficient sleep• 50-70 million Americans suffer from chronic
sleep disorders• Every month, 56 million Americans admit
struggling to keep their eyes open while driving and 8 million fall asleep at the wheel monthly
• 500,000 driving injuries and 55,000 debilitating related injuries occur annually due to fatigue
• 6,400 sleep-related fatalities occur annually
20% of serious & fatal crash injuries
SLEEPMATTERS INITIATIVEBrighamHealthBoston,MA
2
Physician Work Hours, Health, and Patient Safety
3
Percentage of short sleepers (<7h) in the U.S. populationFrom 1965 to 1999
Physician Work Hours, Health, and Patient Safety
Populations at higherrisk for diabetes
Whites African-Americans
Hispanics Other0%
10%
20%
30%
40%
50%
60%
4
24 hours of wakefulness induces performance impairment comparable with blood alcohol concentration 0.10%
5
Characteristics of Sleep
• Ubiquitous: All animals (e.g., mammals, insects)• Obligatory: Animals die if deprived of sleep long
enough• Complex: REM sleep and non-REM sleep• Homeostatically regulated: Amount and content of
sleep depends on prior wake duration (including naps, extended wake)
• If insufficient, waking, performance, alertness, and errors and accidents affected
• Sleep Disorders exist: Associated with other disorders, including cardiovascular disease
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Sleep Regulation
• Homeostatic• Level of sleep
drive• Circadian
• ~24 hour biologic clock
• Regulates timing of sleep and wake
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“If sleep does not serve an absolutely vital function, then it is the biggest mistake the evolutionary process has ever made.”
---Allan Rechtschaffen, leading sleep researcher
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Why Does the Brain Need Sleep?
Brain MaintenanceNeural Connectivity
Waste Clearance
Integration of Daily Learning
Restoration ofEnergy Stores
Memory Consolidation
Cognitive Impairment andAlzheimer’s Disease
Impairment ofCreativity and
Problem Solving
Forgetfulness
Fatigue andSluggishness
SLEEPMATTERS INITIATIVEBrighamHealthBoston,MA
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ATP Levels in the Rat Brain Increase During Sleep
Dworak et al, J Neurosci. 2010 Jun 30;30(26):9007-16
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Changes in Rat Brain ATP Levels with Sleep Deprivation and Recovery Sleep• ATP levels in SD vs.
Controls are lower • Normalize with recovery
sleep
Dworak et al, J Neurosci. 2010 Jun 30;30(26):9007-16
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Reduction in Brain Glucose Uptake in Fatigued Rats
Matsui and Watanabe (2008) in Mechanism of Fatigue Studied in a Newly Developed Animal Model of Combined (Mental and Physical) Fatigue, In: Fatigue Science for Human Health. Springer, Tokyo
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Sleep and Memory
Stickgold and W alker, Trends Neurosci 2005; 28:408-415
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Reductions in Sleep Time May be Associated with Future Learning Problems*
0
2
4
6
8
10
12
>9 >7.5 to <9 <7
Hours of Sleep
Silva et al, SLEEP 34; 2011:1197-1205
Odd
s R
atio
s
*p<0.10
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ARTISTIC RENDITION OF THE GLYMPHATIC SYSTEM
Benveniste et al, Anesth Analg 2019; 128:747
15
Sleep Improves Clearance of β-amyloid from the Brain
Xie et al, Science 2013;342:373-7
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Synaptic Homeostasis Theory
Tononi and Cirelli, Neuron 2014; 81:12
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Role of Sleep in Facilitating Creative Thought
Lewis et al, Trends Cogn Sci 2018;22:491
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Stage 1
Stage
2
Stage 3
REM
Why Does the Body Need Sleep?Heart Health
and BloodPressure
Regulation
Regulation ofAppetite
Maintenanceof Insulin
and GlucoseMetabolism
ImmuneSystem
Regulation
HypertensionHeart Disease
and Stroke
OvereatingWeight Gainand Obesity
MetabolicSyndrome
and Diabetes
↓ VaccinationResponse
↑ Colds and Flu
SLEEPMATTERS INITIATIVEBrighamHealthBoston,MA
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Physician Work Hours, Health, and Patient Safety
0
0.5
1
1.5
2
Unadjusted Fully Adjusted*
<6 h6-7 h7-8 h8-9 h> 9 h
Sleep Duration and Hypertension
n = 5910
*Age, sex, race, AHI, BM I
Sleep Heart Health StudyGottlieb et al. Sleep 2006; 29:1009-14
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Physician Work Hours, Health, and Patient Safety
Short Sleep Duration is Associated with Higher Blood Pressures in Children
Archbold et al. J Pediatr 2012 Jan 25. [Epub ahead of print]
n = 334
60
80
100
120
140
Sys
tolic
Blo
od P
ress
ure
200 400 600 800Total Sleep Time (Minutes)
Baseline Follow-UpFitted values
Total Sleep Time on Systolic Blood Pressure
20
40
60
80
100
Dia
sto
lic B
loo
d P
ress
ure
200 400 600 800Total Sleep Time (Minutes)
Baseline Follow-UpFitted values
Total Sleep Time on Diastolic Blood Pressure
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Sleep Duration and CHDNurses Health Study*
Physician Work Hours, Health, and Patient Safety
Ayas et al. Arch Intern Med 2003;163:205-209
Sleep Duration, h/d
≤5 6 7 8* ≥9
N 67 267 348 193 59
Person-Yrs 30,115 175,629 288,731 162,662 31,015
RR 1.82(1.34-2.41)
1.30(1.08-1.57)
1.06(0.89-1.26)
1 1.57(1.18-2.11)
RR w/o DM/Htn 1.45(1.10-1.91)
1.18(0.98-1.42)
1.09(0.91-1.30)
1 1.38(1.03-1.86)
RR w/DM, Htn 1.39(1.05-1.84)
1.18(0.98-1.43)
1.10(0.92-1.31)
1 1.37(1.02-1.85)
*10 year follow-up
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Physician Work Hours, Health, and Patient Safety
Short and Long Sleep Durationsare Associated with Increased Mortality
Kripke et al. Arch Gen Psychiatr 2002; 59(2):131-6
3 4 5 6 7 8 9 >10
Men
Women
Hours of Sleep
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Physician Work Hours, Health, and Patient Safety
1960 1980 2000Year
10
9
8
7
6
32.9
31.3
30.9
23.3
15.1
14.6
13.3
Average sleep / day(hours)
Percent of U.S.Population Obese
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Risk of Obesity from Childhood to Adolescence Tucson Childrens Assessment of Sleep Apnea Study
Physician Work Hours, Health, and Patient Safety
Silva et al. Sleep 2011; 34(9):1197-1205
Odd
s Rat
io
0
0.5
1
1.5
2
2.5
3
3.5
Short Sleep V. Short Sleep7.5 – 9 hours <7.5 hours
*
* p<.05
N=304
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Daytime Leptin and Ghrelin Levels
Physician Work Hours, Health, and Patient Safety
Spiegel et al. Ann Int Med 2004; 141:846-850
1.5
2.0
2.5
3.0
3.5
9 11 13 15 17 19 21Clock Time
2.2
2.8
3.4
LEPTIN(ng/ml)
GHRELIN(ng/ml)
After 2 days of10-h bedtim es
After 2 days of4-h bedtim es
p level % change
Leptin 0.041 -19%
Ghrelin 0.038 +24%
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Ratings of Hunger and Appetite
Physician Work Hours, Health, and Patient Safety
Spiegel et al. Ann Int Med 2004; 141:846-850
Hunger
Global Appetite
After 2 days of10-h bedtim es
After 2 days of4-h bedtim es
p level % change
Hunger (cms) <0.01 +19%
Global Appetite (cms) 0.010 +20%
9 11 13 15 17 19 21Clock Time
3.5
5.5
7.5
22
32
42
52
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Insufficient Sleep and Obesity: Possible Mechanisms
Insufficient Sleep
Increased GhrelinDecreased Leptin
Greater Appetite
Increased Fatigue
Less Physical Activity
Weight Gain
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Impact of Sleep Restriction on Glucose Disposition
Physician Work Hours, Health, and Patient Safety
Spiegel et al. Lancet 1999; 354:1435-9
Odd
s Rat
io
0
1
2
3
4
5
6
Kg AIRg Sg DI
Rested5 d Slp Restr
Kg=Glu Tol (%/min)AIRg=Ins Resp (mU/mL/minx100Sg=Glu Eff (%/min)DI=Disp Index (Ins Resp/Ins Sens x1000)
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Short Duration of Sleep and Incidence of Type 2 Diabetes
Physician Work Hours, Health, and Patient Safety
Cappuccio et al. Diabetes Care 2010; 33:414-420
Com bined effect (random m odel): P=0.024; n=90,623Num ber of incident cases: 3,079
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Insufficient Sleep and Diabetes
• Risk of Type 2 Diabetes 30% higher in persons who sleep less than 6 hours per night
• Increased risk of metabolic syndrome• Mechanisms
• Reduction in insulin secretion• Elevation in cortisol• Increased sympathetic nervous system activity• Mediated by increased obesity (from insufficient sleep)
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Insufficient Sleep and Diabetes
Less evidence for impact of insufficient sleep and Type 1 diabetes• Insulin effectiveness decreased with <4 hours sleep• Short sleep duration=worse diabetic control• Preliminary data in children show sleep extension decreases glucose
variability
32
Effect of Sleep Extension on Glucose Variability in a Child with Type 1 Diabetes
Courtesy of Dr. M ichelle Perfect
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Risk of a Cold and Sleep Deficiency
Prather et al, Sleep 2015;38:3153
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Antibody Response to Hepatitis B Vaccination as a Function of Sleep
Example: Impact of 2-2.5 H Sleep Deficiency on Tennis Serving Accuracy
Reyner and Horne, Physiol Behav 2013; 120:93-6
Effect of Sleep Extension on Basketball Players
Mah et al, Sleep 2011;34:943-50
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Safety Impacts of Too Little Sleep
Drowsy driving is a RED ALERT!
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Being awake for 18 hours is sim ilar to being legally drunk
37
Mental Impact of Sleep Deficiency
• Longer reaction time
• Lapses in attention or concentration• Lost information• Errors of omission• Poor short term memory• Poor mood (increased fatigue, confusion, stress, and irritability)• Reduced motivation• Sleepiness
• Distractibility• Poor performance (at circadian low points, when sedentary, on long, difficult, or externally
paced tasks with no feedback, in unchanging sound, particularly with reduced light or sound and low motivation, interest, or novelty)
Bonnet and Arand Sleep Med Rev 2003; 7:297-310
38
Reaction Tim e(sec)
Cohen et al. Science Translational Med 2010
Effects of Insufficient Sleep Worsen…
• Within a day• Across days
Can’t learn to live with less sleep
5.6 h/night
8 h/night
39
Self-assessment Problem With Insufficient Sleep
Objective Subjective
Van Dongen et al., SLEEP 2003.
40
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TimingDuration Quality
What is Healthy Sleep?
Duration Timing Qualityo Adults need at least
7 hours of sleep per night
o Children and adolescents require even more
o Sleepiness is one sign you aren’t getting enough sleep
o A consistent nightly sleep pattern is critical to keep the body clock that regulates sleep in synch with the 24-hour day
o Genetic factors influence whether you prefer to wake up early or stay up late (morning types versus evening types)
o Consolidation of sleep into 1 or 2 major bouts is important to optimize the restorative value of sleep
o Many sleep disorders fragment sleep, or interfere with sleep maintenance or sleep consolidation
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Biological Factors That Cause Fatigue
Hours Awake
Time of Day
Sleep DebtSleepyou
Need
SleepyouGet SLEEP DEBT
Sleep Disorders Sleep Inertia
43
Sleep WakeDisorders(>90 Total)
InsomniaDisorder
ObstructiveSleep Apnea
(OSA)
Shift WorkDisorder
Restless Leg Syndrome
(RLS)
44
Individual Behavior and Sleep
02468
1012
Bedtime Email/ Text No B edtimeEmail/ Text%
<6
Hour
s Sle
ep
Impact of Email/Texting at Bedtime
N=1083
45
Economic Impact of Sleep Deficiency and Sleep Disorders
• Shift work: $65.2 Billion• Absenteeism, Accidents, Lost productivity• Increased medical illnesses• Personnel Turnover
• Sleep Disorders: $100 Billion
46
March 24, 1989• ~258,000 barrels of oil
spilled in Prince William Sound Alaska
• Economic cost: Billions
• Environmental cost: Incalculable
47
*NTSB Safety Recom m endation, Sept 18, 1990
EXXON VALDEZ
•Greatest ecological disaster in the history of mankind•Urban Legend: The ship’s captain was intoxicated.•Fact*: At the time of the grounding, the ship was under the navigational control of the 3rd mate. “…he could have had as little as 5 or 6 hours of sleep in the previous 24 hours.”
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This program increased sleep duration, improved
sleep quality, and reduced daytime sleepiness.
Improved Health and Safety following Sleep Health Education and Sleep Disorder Screening Programs
Reduced injuries and disability day usage– 24% fewer injuries and a 46% reduction in disability day
usage ($2.2 million annual savings).
Sullivan et al. Sleep. 2017;40:1-10.
5-fold higher rate of serious preventable crashes among truck drivers diagnosed with OSA who were not compliant with treatment
Burks et al. Sleep. 2016; 39: 967-75.
Crash rate am ong adherent group only 20% as high as those who were not adherent to treatm ent.