Improving the Snooze What is Sleep Anyway???? What Regulates Sleep? Sleeping better as we age 1. Homeostatic Process sleepy The longer you’re awake, Howell Foundation Luncheon the more sleepy you feel. A wake August 25, 2017 2. The Circadian Process Sleep (Biological Clock) sleepy You feel sleepier at certain times of day than Andrea Z. LaCroix, PhD Professor and Chief of Epidemiology others, and the times can Director, Women’s Health Center of Excellence change. A wake Sleep UC San Diego Germain A, Buysse DJ. Brief behavioral treatment of insomnia. In: Perlis M, et al. (eds.). Behavioral treatments for sleep disorders , pp. 143-150. Elsevier, 2011. Why Does Sleep Go Bad??? Stages of Sleep Sleep Cycles During the Night • Age-related change in sleep mechanisms There are 5 stages of sleep Changes in homeostatic sleep drive and circadian Least rhythm for wakefulness (accelerated by dementia) We cycle through all of them, several times Modifiable • Primary sleep disorders a night Obstructive sleep apnea, restless legs syndrome, • Stage 1 = transition from wake to sleep REM behavior disorder • Other co-morbid medical and psychiatric • Stages 2 – 3(4) = increasingly deep sleep illnesses • REM = Rapid Eye Movement (dream) sleep Pain, depression, medications Most • Environmental and behavioral factors Modifiable • Any combination of the above SleepMultiMedia, Version 6.0, Scarsdale, NY Bloom et al. J Am Geriatr Soc . 2009; 57(5): 761-789; McCurry et al. Sleep Med Rev . 2000; 4:603-608. Changes with Age: Percentage Changes with Age: Awakenings Changes with Age: Mid-Day Naps Sleep Stage Williams, et al.1974. Electroencephalography (EEG) of human sleep: Clinical applications. John Wiley & Sons Williams, et al.1974. Electroencephalography (EEG) of human sleep: Clinical applications. John Wiley & Sons Williams, et al.1974. Electroencephalography (EEG) of human sleep: Clinical applications. John Wiley & Sons GHRI T-32 Journal Club_McCurry 3/11/14 1
Circadian Rhythm Changes: Advanced Primary Sleep Disorders Sleep and Alzheimer ’ s Disease Sleep Phase Obstructive sleep apnea (OSA) Sleep architecture changes resemble an • Overlapping risk factors for stroke (HTN, diabetes, atrial acceleration of age-related changes fibrillation, cardiac and carotid disease) Sleepy, Wake Loss of neurons that regulate sleep-wake • Widely underdiagnosed; compliance w/CPAP often poor Normal Go to bed Up cycles Periodic leg movement syndrome (PLMS) Phase • SCN: the body’s internal circadian “clock” Restless legs syndrome 1600 1800 2000 2200 2400 0200 0400 0600 0800 1000 • Subcortical structures • Linked to low iron levels • Thermoregulatory processes • In persons with dementia more strongly associated with Advanced nocturnal agitation than OSA and PLMS • Disruptions in hormonal production systems Phase REM sleep behavior disorder (RBD) Changes more prominent in persons with Sleepy Go to bed Wake up • Most common in older men more advanced dementia Philips B, et al. 2000. Arch Intern Med, 160: 2137-2141 Gehrman PR, et al. 2003. J Am Geriatr Psychiatry, 11: 426-433 Ancoli-Israel, S. 1996. All I want is a good night’s sleep. Mosby. Wu YH, Swaab DF. 2007. Sleep Med, 8:623-636. Young T, et al. 2004. JAMA, 291:2013-2016. Rose KM, et al. 2011. Sleep, 34:779-786 Other Medical Correlates of Insomnia Drugs that Can Worsen Sleep Environmental & Behavioral Causes Pain • Alcohol • Noise • Arthritis, malignancy, dental, constipation • CNS stimulants (e.g., caffeine, theophylline, • Light Organ-system failures nicotine) • Temperature • Congestive heart failure, angina • Beta-blockers, calcium channel blockers • Season of year • COPD, Asthma • Bronchodilators • Bedding • Benign prostatic hyperplasia, incontinence, UTIs • Corticosteroids • Television • GI upset (heartburn, reflux) • Decongestants • Dietary practices • Hypothyroidism • Exercise routines • Diuretics Psychiatric conditions • Stimulating antidepressants, cognitive enhancers • Pets • Depression, anxiety • Roommate or bed partner behaviors Menopause • Thyroid hormones Roszkowska J, Geraci SA. 2010 Am J Med, 123:1087-1090. Points to Remember #1 So What Can We Do About It??? Treatment Strategies Treatment for Sleep disturbances are common in insomnia the general population and their causes are complex and multi- factorial. Behavioral Pharmacologic (CBT-I) GHRI T-32 Journal Club_McCurry 3/11/14 2
Sedating Medications and Aging Pharmacological Approaches Advantages of CBT for Insomnia Hypnotics – Benzodiazepines Don ’ t always help or they stop working Addresses perpetuating and, in some cases, Hypnotics – Benzodiazepines Receptor Agonists (BZRAs) Can cause unwanted side effects (poor precipitating causes of sleep disturbances • Zaleplon ( Sonata ) balance, confusion, paradoxical reactions) • Zolpidem ( Ambien, Ambien-CR* ) No interactions with other medications or side • Eszopiclone ( Lunesta* ) Primarily tested in younger adults with different effects Melatonin agonists pharmacokinetics • Ramelteon ( Rozerem*) Can improve symptoms of comorbid conditions Antidepressants Polypharmacy is always a concern • Doxepin (Silenor*) Can reduce need for long-term hypnotic Others agents currently available or in development: Not preferred by many older adults medications • OTC - Melatonin, valerian, anti-histamines, etc. Few randomized efficacy trials with specialty Empowering for patients; provides tools they • Prescription - Anti-depressants (e.g.,trazodone), anti- psychotics, HTN meds (prazosin; PTSD nightmares) populations, e.g., persons with dementia can use in future situations • In development –5HT, GABA and Hypocretin/Orexin An RCT of Telephone-Based Cognitive Behavioral Significance Specific Aims Training for Insomnia in Midlife Women with Vasomotor Symptoms • All women experience menopause; a majority also experience 1. Evaluate feasibility, acceptability, and treatment fidelity of S.M. McCurry 1 , K.A. Guthrie 2 , C.M. Morin 3 , N.F. Woods 1 , telephone-based cognitive behavioral therapy for insomnia insomnia symptoms during this time of life C.A. Landis 1 , J.C. Larson 2 , L.S. Cohen 4 , K.E. Ensrud 5 , (CBT-I) vs. menopause education condition (MEC) J. Hunt 2 , H. Joffe 4 , K.M. Newton 6 , J.L. Otte 7 , S.D. Reed 1 , B. • Menopause-related sleep disturbance places substantial Sternfeld 8 , L. Tinker 2 , and A.Z. LaCroix 9 2. Determine efficacy of CBT-I vs. MEC on improving: economic burden on women and society a) Primary outcome of insomnia symptoms assessed by 1 University of Washington, Seattle WA • Sleep problems are a leading reason for visits to health care Insomnia Severity Index (ISI) 2 Fred Hutchinson Cancer Research Center, Seattle WA professionals during menopause 3 Universite Laval, Quebec, QC, Canada b) Secondary outcome of self-reported sleep quality 4 Harvard Medical School, Boston MA • Evidence-based treatments for insomnia symptoms in 5 University of Minnesota, Minneapolis, MN assessed by Pittsburgh Sleep Quality Index (PSQI) 6 Group Health Research Institute, Seattle, WA postmenopausal women are lacking 7 Indiana University, Indianapolis, IN c) Exploratory outcomes measuring daily diary ratings of 8 Northern California Kaiser Permanente • Effective, cost-efficient, non-pharmacological treatments are sleep variables and vasomotor symptoms, and self- 9 University of California, San Diego, La Jolla, CA needed that can be integrated into primary care reported symptoms of depression, anxiety, bodily pain, MsFLASH-04 study supported by the Fred Hutchinson Cancer and quality of life Research Center, Seattle, WA (1U01 AG032699) Intervention Eligibility Bed Restriction • If you reduce your time in bed, you increase your time awake 40-65 years old, in the menopausal transition or Age/menopau se postmenopausal • Being awake longer will help you fall asleep faster and stay asleep for more of the night ISI >12 (the observed median in other MsFLASH Sleep trials) • How long should I stay in bed? Hot Flashes > 2 hot flashes per day on average over 2 weeks • Keep a sleep diary for 5 – 7 days Accessibility by a daily diary Consent • Write down time you went to bed, time you got up, Available by telephone during the 8-week and estimate how much of that time you were asleep intervention • Bed restriction time = estimated week sleep time Written informed consent signed average plus 30 minutes GHRI T-32 Journal Club_McCurry 3/11/14 3
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