Diagnosis and Treatment of Sleep Disorders in Dementia

1. Diagnosis and Treatment of Sleep Disorders in Dementia SubhashBashyal, M.D. George T. Grossberg, M.D. Samuel W. Fordyce Professor Department of Neurology & Psychiatry Saint Louis University School of Medicine

2. Disclosures Dr. Bashyal – None Dr. Grossberg Consultant – Baxter Bioscience; Bristol-Myers, Squibb; Forest Labs; Novartis; Lundbeck; Otsuka Research Support: Baxter Bioscience; Janssen; Novartis; Pfizer; NIH Safety Monitoring Committee - Merck

3. Dementia • Characterized by cognitive decline resulting in functional impairment. • Major types: Alzheimer's Dementia Lewy Body Dementia Vascular dementia Parkinson’s Dementia Frontotemporal dementia

4. Epidemiology • 1/8 older Americans has Alzheimer’s disease (AD) • 5.4 million Americans with AD and other dementias • Estimated to cost 200 billion USD (Alzheimer’ s Association 2012) • Risk increased in the presence of cardiac disease, hypertension, and cerebrovascular disease, but presence of dementia alone has been associated with decrease in mean survival. Ref: Alzheimer’s Disease Facts and Figures – 2012 www.alz.org

5. Normal Sleep • NREM: Stages 1, 2, 3 and 4. • Stages 3 and 4 also known collectively as deep sleep, delta sleep, slow wave sleep. • REM sleep • Cycle occurs approximately every 90 mins. • Regulated by circadian rhythm, homeostatic sleep drive. Ref: Weldemichael DA, Grossberg GT, Int J AlzheimersDis, 2010

6. Sleep changes in the Elderly • Difficulty in sleep initiation • Decrease in total sleep time • Reduced sleep efficiency • Decrease in slow wave and REM sleep and an increase in Stage 1 and 2 • Increased fragmentation of sleep.

7. Ref: Kate Crowley, Neuropsychol Rev 2011

8. Changes in sleep in patients with Alzheimer's disease • Poorer sleep efficiency • Longer sleep latency, increase in Stage 1 • Frequent awakenings, and decrease in REM sleep, decrease in sleep spindles and K complexes • Frequent day time naps • Circadian rhythm disturbance, sundowning • Phase delay

9. Dementia and Sleep • Sleep disordered breathing associated with cognitive impairment.( Yaffe et al) • REM-sleep behavior disorders associated more with Lewy Body dementia.(Bliwise et al ) • Nocturnal sleep disturbance associated with more advanced Alzheimer's disease • Poor sleep leading to increased wandering with risk for injury and care giver burden, and frequently is a factor for increase in level of care . Ref: Yaffe K, Laffan AM, Harrison SL, et al, JAMA 2011 Bliwise DL, Mercaldo ND, Avidan AY, et al, Dement GeriatrCognDisord.

10. Causes of sleep disturbance in dementia • Apolipiprotein E associated with sleep disturbance (in Alzheimer’s disease) • Sleep related breathing disorders • Circadian rhythm disorders • Medications • Comorbid depression / anxiety • Medical problems: Pain, cardiovascular, respiratory, GI and urological problems. • Environmental Factors.

11. Evaluation History (from sleep partner if available): Evaluate for common causes Patient’s medications, including over the counter and herbal supplements History of snoring/ periodic cessation of breathing, kicking during sleep Physical examination / Mental Status Examination Lab tests Sleep study / sleep clinic

12. Obstructive sleep Apnea • Higher prevalence in elderly with dementia, and also higher with severity of dementia • Similar comorbid factors as Alzheimer’s dementia: Increasing age, cardiovascular parameters (hypertension, cardiac disease, stroke) and Apolipoprotein E genotype • Managed by weight loss, avoidance of alcohol, sedatives and hypnotics • Treated with Continuous Positive Airway Pressure (CPAP)

13. Restless Leg syndrome(RLS) • Characterized by distressing, deep sensations in the limbs ( predominantly lower), and an urge to move them (mostly at night) • More frequent in women • Associated with conditions such as low serum ferritin, renal failure, rheumatoid arthritis, anti depressant use • Treated with dopamine agonists (pramipexole, ropinirole, L-Dopa/Carbidopa – off label) • Periodic limb movements(PLMs): Often co exist with RLS, no treatment recommended if alone (w/0 RLS) Ref: Neikrug AB, Ancoli-Israel S, Gerontology 2010

14. Treatment of Insomnia in patients with dementia • Non pharmacological methods: • Bright light therapy: Some benefit with reductions in night time sleep fragmentation, increase in sleep period • Behavioral methods :(increase in daytime physical activity, daily sunlight exposure, decreased night time noise and light) Some benefit with reductions in sleep fragmentation, but mixed results overall Ref: Neikrug AB, Ancoli-Israel S, Gerontology 2010

15. Pharmacological treatment • Sedative Hypnotics: Non-Benzodiazepines ( Zolpidem Zaleplon) preferred to Benzodiazepines, with decreased risk of disorientation and memory loss • Melotonin: Mixed results but mostly ineffective ; effect better when combined with bright light therapy. • Acetylcholinesterase Inhibitors: Some positive results with Donepezil in AD. • Antipsychotics: Few studies evaluating sleep, more helpful for agitation. Increased sensitivity in patient’s with Lewy Body Dementia, use with caution in elderly • Anti depressants: Mirtazepine and Trazodone Ref: Wilson SJ, Nutt DJ, Alford C, et al. J Psychopharmacol 2010

16. Other Contributing factors • Low stimulus non distracting environment • Avoid frequent interruptions (e.g. Vitals check at night while in a nursing home) • Sleep Hygiene • Treatment of pain/ urinary issues • Treatment of sleep apnea, restless legs syndrome • Treatment of medical problems

17. Summary • Sleep problems in patients with dementia have been known to cause impaired daytime functioning ,and are frequently responsible for the requirement of a higher level of care • Alzheimer’s disease has been associated with circadian rhythm disorders, sleep breathing disorders, which can further impair cognition and contribute to behavioral problems • Behavioral management is associated with the least side effects, while the use of medication needs more research.