SLEEP AND THINKING, MOVING, AND FEELING

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SLEEP AND THINKING, MOVING, AND FEELING

• Andrew A. Monjan, Ph.D., M.P.H.
• Chief, Neurobiology of Aging Branch
• Neuroscience and Neuropsychology of Aging Program
• National Institute on Aging

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BOTTOM LINES

• Strong body of data directly interrelating sleep
  problems with mood disorders
• Growing data base directly associating sleep
  disorders with attention and memory problems
  cognitive-based therapies improve sleep, and
  cognitive states may produce disordered sleep
• Motor disorders, especially involving the
  dopaminergic system, may produce sleep disorders
  possible association between sleep problems and
  falls
• Sleep and health are directly interrelated

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Prevalence Estimates of Sleep Problems in the
Elderly
Chronic Sleep Problem Prevalence Any Sleep
Complaint 57 Sleep Apnea
24 PLMS 45 RLS
11 Insomnia 29 Early Morning
Awakening 19
Ancoli-Israel, et al., 1991 Foley, et al., 1995
Phillips, et al., 2000
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INSOMNIAPrevalence by Age Group
Percent
Age Group
Mellinger, et al., 1985 Foley, et al., 1995
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INSOMNIA Percent Prevalence and Incidence
Percent
Foley, et al.,1995 1998
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Late Age Sleep Architecture
Middle Age Sleep Architecture1
Stage 1 (5)
Stage 1 7)
REM (16)
REM (25)
Stage 3/4 (9)
Stage 2 (45)
Stage 3/4 (25)
Stage 2 (68)
n718
1Source Ancoli-Israel, 1996
Foley, et al., 2002
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NEUROBIOLOGICAL MODEL OF SLEEP FRAGILITY IN
LATE-LIFE
Cortex (esp. PFC)
Cingulate
Thalamus
Basal Forebrain, Post. Hypothal, Amygdala,
Hippocampus
Ant. Hyp
ARAS
Nofzinger, et al.
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PROJECTIONS OF THE VENTROLATERAL PREOPTIC NUCLEUS
(VLPO) INHIBITING AROUSAL SYSTEMS
Sapir, et al., 2001
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INFLAMMATORY PATHWAYS MODULATING SLEEP
Bryant, et al., 2004
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Percent of Adults Who Usually Slept 6 Hours or
Less a Night, by Sex and Age United States,
1985 and 2004
Men
Women
National Health Interview Survey
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NSF, 2003
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2003 Sleep in America Poll Methodology

• Telephone survey of 1,506 adults aged55 to 84
  living in the continental USA
• About 23 of qualified persons agreed to
  participate
• Conducted by WBA Market Research between
  September 17 and December 10, 2002
• Margin of error no more than 2.5 for the
  entire sample
• Up to 5.6 for sub sample comparisons

NSF, 2003
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Reported Hours Slept Older Vs. Younger American
Adults
NSF, 2003
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Sleep Problems and Depression


NSF, 2003 Foley, et al., 2004
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Sleep Problems and Heart Disease


NSF, 2003 Foley, et al., 2004
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Sleep Problems and Lung Disease



NSF, 2003 Foley, et al., 2004
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Sleep Problems and Stroke

NSF, 2003 Foley, et al., 2004
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Sleep Problems and Multiple Medical Conditions
NSF, 2003
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Insomnia in Older Americans Symptoms Vs.
Diagnosis Vs. Treatment
Percent
_
_
_
National Sleep Foundation, 2003
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Sleep Problems and Exercise
NSF, 2003
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2003 Sleep in America Poll Summary Findings

• Older adults report getting same amount of sleep
  as do younger adults
• Sleep problems in older adults are associated
  with medical illness, rather than aging per se
• Individuals with multiple medical problems have a
  particularly high risk of sleep problems
• Bodily pain, exercise frequency, ambulatory
  limitation, and obesity are related to sleep
  problems in older adults

NSF, 2003
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Overweight and Obesity
National Health Interview Survey
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Measured Obesity among People age 65
Percent
Source National Health and Nutrition Examination
Survey, selected years
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Sleep Problems and Overweight (Body Mass Index)


NSF, 2003 Foley, et al., 2004
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Implications of short sleep for glucose regulation
Environmental/Behavioral
Genetic Factors
Factors

• Poor Diet

• Sedentary Lifestyle

• Normal Aging

• Chronic Stress

• Sleep Loss

Insulin Resistance
METABOLIC SYNDROME
TYPE 2 DIABETIES
Van Cauter
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GLUCOSE TOLERANCE Kg derived from glucose
disappearance curve during IVGTT CLINICAL
SIGNIFICANCE
18-27 yr old subjects fully rested 2.40 0.41
18-27 yr old subjects in sleep debt 1.45 0.31
Kg ( per min) Kg ( per min)
21-30 yr old fit subjects (2) Range 2.20 - 2.90
61-80 yr old adults with impaired glucose
tolerance (1) Range 1.30 - 2.10
(1) from Garcia et al, J Am Geriatr Soc 45
813-7, 1997. (2) from Prigeon et al, Metabolism
44 1259-63, 1995. Courtesy of Eve Van Cauter
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Metabolic Phenotypes of the Clock mutant model
Turek Bass, 2006

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SIMILARITIES BETWEEN SLEEP LOSS AND AGING

• Function
• Glucose tolerance
• Insulin sensitivity
• C-reactive protein
• Cardiac sympathetic activity
• Plasma norepinephrine
• Evening cortisol levels
• Plasma TSH levels
• Plasma leptin levels
• Mood
• Vigilance
• Subjective alertness

• Sleep Loss Aging

Van Cauter
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Sleep Problems and Bodily Pain

NSF, 2003 Foley, et al., 2004
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SLEEP AND PAINStudy Design

• Subjects meeting diagnostic criteria for
  co-morbid OA and chronic insomnia were randomized
  to either
• Standard CBT-I (Eight 2-hour sessions).
• Stress Management and Wellness (SMW)
  intervention.
• Neither intervention specifically mentioned pain
  management although SMW contained components
  typically included in behavioral pain
  interventions.
• Problem-solving, goal setting, cognitive
  approaches to reducing stress and anxiety,
  interpersonal skills training, and exercise
  enhancement

Vitiello, et al., 2007
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Study Design

• Subjective sleep quality (two-week log) and
  self-reported pain (MPQ and SF-36P) were assessed
  pre and post-treatment for CBT-I and SMW.
• CBT-I, but not SMW, subjects were assessed again
  at one year.
• Ten SMW subjects crossed over to CBT-I treatment
  and were followed up at one year.

Vitiello, et al., 2007
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Vitiello, et al., 2007
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Conclusions

• CBT-I improved both immediate and long-term
  self-reported sleep quality in this sample of
  older OA patients with co-morbid insomnia. The
  observation of CBT-Is long-term impact on sleep
  in this co-morbid sample is a new finding.
• CBT-I, without specifically addressing pain
  management, reduced both immediate and long-term
  reported pain in these OA patients.
• SMW failed to reduce pain despite containing
  several components typically included in
  effective behavioral interventions for management
  of chronic pain.

Vitiello, et al., 2007
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Prevalence Rates Of Sleep Disturbances InPersons
With Dementia And Their Family Caregivers
McCurry, et al. Sleep Medicine Reviews, 2007
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SLEEP AND COGNITION (1)

• A number of research studies, both
  cross-sectional and longitudinal, have shown that
  disturbed sleep has a negative impact on
  cognitive functioning and quality of life.
• Both animal and human studies especially
  implicate sleep as important for the process of
  memory consolidation following initial learning.
• Many studies have demonstrated the benefit of
  sleep on the acquisition of a motor skill, with
  the greatest improvements in recall following the
  interval in which sleep had occurred (amount of
  overnight improvement correlated with the amount
  of NREM and REM sleep experienced), indicating
  that performance improvements are specifically
  related to sleep processes.

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SLEEP AND COGNITION (2)

• It has been proposed that age-related changes in
  sleep patterns may be linked to changes in the
  glucocorticoid system, including the hippocampus,
  which occur with age.
• In animal studies, sleep deprivation interferes
  with the encoding of hippocampal-mediated tasks
  (even 5-hours of pre-training deprivation
  disrupts the encoding of avoidance learning).
• At the cellular level, sleep deprivation reduces
  the basic excitability of hippocampal neurons as
  well as significantly impairing long-term
  potentiation.

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SLEEP AND COGNITION (3)

• Thus, there has accumulated a sufficient base of
  data and converging lines of evidence to suggest
  that sleep loss associated with aging may be a
  contributing factor to some of the cognitive
  decline commonly seen in later life, as well as
  being a comorbid condition contributing to other
  metabolic, medical, and behavioral conditions in
  aging populations.

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SOME CONSEQUENCES OF DISORDERED SLEEP IN THE
AGING POPULATION

• Excessive daytime sleepiness
• Attention and memory problems
• Depressed mood
• Nighttime falls
• Overuse of hypnotic drugs and OTC medications
• Possible adverse interactions with co-morbid
  conditions, e.g. sleep apnea and CVD
• Lowered quality of life
• Metabolic dysfunction

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Evidence for Co-Occurrence
Cognitive Disability
EmotionalDisability
Sleep Disorder
PhysicalDisability
Adapted from Anne Newman
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Questions for the Future

• What constitutes normal and optimal sleep in the
  elderly?
• Are there different causal mechanisms or
  co-factors with onset of sleep disorders late in
  life than earlier in life?
• Can sleep loss can increase the stress load,
  possibly facilitating the development of chronic
  conditions, such as obesity, diabetes, and
  hypertension, which have an increased prevalence
  in low SES groups?
• What interventions and therapies are most
  effective and appropriate for the older
  population?

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Further Questions for the Future

• What are the brain mechanisms underlying
  age-dependent changes in sleep?
• What are the relationships between sleep and
  cognitive functioning in later life?
• Are there relationships between sleep, nocturia,
  and falls?
• How does sleep affect aging and disease, and,
  conversely, how do aging and disease affect sleep?