Sleep well, think well: Strategies for improving sleep in dementia

PROFESSOR SHARON NAISMITH, MAPS, CCN NHMRC CAREER DEVELOPMENT FELLOW LEONARD P ULLMAN CHAIR, HEAD, HEALTHY BRAIN AGEING PROGRAM, BRAIN & MIND CENTRE

The University of Page 1 The significance of sleep

– Important for: – Mood – Alertness – Daytime functioning & cognition

– 2 key systems: – Sleep system – Circadian system

The Page 2

How does sleep change as we age?

– Shallow, fragmented – Decreased deep sleep – Decreased dreaming (REM) in second half of night – Decreased sleep duration – Daytime sleepiness – Shift to earlier sleep and wake times – Longer to recover from lack of sleep and changes in timing – Elderly twice as likely to be prescribed sleeping pills than younger people

The University of Sydney Page 3 Why should we be concerned about sleep disturbance?

– Prodromal feature of: – Mood disorders – Neurodegenerative disorders • Parkinsons Disease • Dementia with Lewy Bodies • Alzheimer’s Disease – Bi-directional association between B-amyloid and poor sleep – Predictive of: – More rapid cognitive decline

The University of Sydney Page 4 How is sleep linked to cognitive decline?

Z • Clearance of toxins & waste • Memory consolidation Z Role of Z sleep • Immune/inflammatory regulation • Support of new brain cells

• Common in dementia and MCI Impaired sleep • Predicts worse cognitive quality outcomes

• Fragmented sleep Obstructive sleep • Hypoxemia apnoea

The University of Sydney Page 5 What happens to sleep in dementia? Alzheimer’s – 40-50% - sleep disturbance – Excessive daytime sleepiness – Light fragmented sleep, ~40% of nocturnal time awake – Daytime napping – Sleep apnoea 35-63% (48% have AHI>20) Dementia with Lewy Bodies – Disturbance may occur in up to 90% of patients – Highly prodromal – poor sleep quality and REM Sleep Behaviour Disorder may occur 20 years before the onset Vascular Dementia Commonly associated with obstructive sleep apnoea

The University of Sydney Page 6 Bonanni et al, 2005; Cooke et al, 2006

How does poor sleep impact on functioning? – Circadian delay – Contributes to sundowning – agitation and confusion in the evening – Difficulty sleeping at night – Wandering can increase risk of injury and in turn medical problems and can lead to need for care

– Excessive sleepiness in daytime – Poorer cognitive functioning – Uncontrolled naps – Impacts on driving – Decreased engagement in socialisation and therapies

The University of Sydney Page 7 SLEEP TO REMEMBER?

NREM Sleep Z Z

Z

11-15Hz

Sleep spindles

Impaired memory processing

The University of Sydney Page 8 External factors affecting sleep Factors that impact sleep

Napping Bed and wake times Exercise

Body Sleep Sleep hygiene temperature quality

Light exposure Depression & stress -TV -Needing to use bathroom -Internet Sleep expectations -Medications

The University of Sydney Page 9 Interventions for sleep- wake disturbance in ageing

The University of Sydney Page 10 Beware drugs!

Cholinesterase Benefits to dreaming (REM) sleep in some studies, Inhibitors Donepezil – more Stage 2 and less Stage 1 sleep Can cause insomnia, disturbing dreams, REM sleep behaviour disorder, dosing could be moved to early in daytime Antidepressants May suppress REM, insomnia, data lacking for efficacy in sleep Antipsychotics May worsen sleep-wake disturbance in AD

Sedative hypnotics Less disruption to sleep architecture No known data on cognitive effects in older people Benzodiazepines Decrease SWS & REM, reduce latency & awakenings Associated with sleepiness, falls, cognitive side-effects, confusion, Short-term (1-2 weeks) use only Clonazepam often effective for REM Sleep Behaviour Disorder Dopaminergic Can cause daytime sleepiness

The University of Sydney Page 11 Naismith, Rogers, Lewis (i2011); Cooke et al, 2006 Does melatonin work for sleep disturbance in AD?

– A powerful antioxidant & free radical scavenger – Helps to clear harmful reactive oxygen species and reduce oxidative stress levels in brain tissue – 14 melatonin studies in AD – 8 reports (n=89), 6 double-blind RCTs (n=210) – Doses: 1-9mg, evening or bedtime – Duration: 2 weeks to 36 months – Improvements in sleep quality, sundowning and cognition in 4/6 randomised controlled trials (N=143)

– Important to use melatonin manufactured in controlled settings e.g Circadin – speak to GP – Combination of light and melatonin may have superior The University of Sydneyeffects Page 12 Cardinali et al, 2010; Dowling et al, 2008; Riemersma et al, 2007

Light therapy

General principles: – Evening exposure delays sleep – Morning exposure advances sleep – Magnitude of circadian shifts depends on intensity and duration - brighter and longer duration produces larger shifts – Short wavelength light (blue light) has greatest effects Efficacy: – Reduction in nightime awakenings in dementia – Benefits best for morning light and if sleep complaints (latency, efficiency, awakenings, total sleep time) – May have broader effects on cognition and mood in AD – 4wks bright light (1000lx) all day

The University of Sydney Page 13 Pay attention to snoring and apnoea: CPAP treatment works!

– San Diego study, n = 39-52 – Less light sleep and awakenings, more deep sleep – Reductions in excessive daytime sleepiness – Improvements in memory

– Sustained effects of CPAP – Cooke et al, 2009: n = 10, 1-year follow-up (CPAP n = 5 vs. no CPAP) – Medium to large effect size improvements in executive functions, psychomotor speed, mood, daytime sleepiness

The University of Sydney Page 14 Ancoli-Israel et al., 2008; Chong et al, 2006; Cooke et al, 2009 1 4 Avoid contributors to sleep problems

– Avoid caffeine  Decreases slow wave ’deep’ sleep  Increases awakenings  Increases time to fall asleep  Can be helpful if wish to delay sleep – Avoid alcohol  Sedative but disruptive – Avoid heavy meals prior to bedtime – Avoid heavy exercise prior to bedtime – Avoid raising body temperature (hot baths) – Consider medications – sleeping medications are only effective for short-term use (<2 weeks)

The University of Sydney Page 15 Practice sleep-promoting activities

– Engage in daytime exercise – Keep the brain active! – Quiet and relaxing activities before bed – Keep lights dim in the evening – Get up at the same time everyday – Ensure morning light exposure – Manage depression and stress – ?Naps

The University of Sydney Page 16 Use of Naps

› Prescribed ‘controlled napping’ • Duration is important! • Nap less than 30minutes • Nap earlier in day, not in evening • Counts in your total sleep count

› May improve alertness, cognition, mood

› Can be associated with sleep inertia (feeling ‘groggy’) if nap for too long

› Consider effects on night-time sleep

The University of Sydney Page 17 If you can’t sleep!

– Get up! – Relax in a different environment • Dim lighting • Do not stimulate the mind – Do not try to make up for lost sleep – Do not focus on the ‘perceived negative” consequences of poor sleep – Consider sleep expectations

The University of Sydney Page 18 Dealing with daytime sleepiness

› Limit the number of demanding activities you perform each day

› Schedule activities that are cognitively and physically demanding for periods when you feel most alert

› Take regular rest breaks

› Ensure adequate light exposure

The University of Sydney Page 19 Summary

– Sleep is important for optimising brain health and consolidating memories overnight – Improving sleep is best achieved using non-drug methods – Implementing lifestyle changes, reducing sleeping pills, having a regular sleep routine, exposure to light and regular exercise, and considering sleep expectations will help

The University of Sydney Page 20 Concerns about cognition or sleep?

– Neurosleep clinic – Healthy Brain Ageing Clinic – Brain and Mind Centre – 94 Mallett Street, Camperdown – Phone: 9114 4002 – Fax: 9351 0551 – Email: [email protected] – http://sydney.edu.au/brain-mind/patient-services/clinics/healthy-brain- ageing.php

NEUROSLEEP NHMRC Centre of Research Excellence

– Healthy Brain, Healthy Sleep

– Postdoctoral Fellowships, Postgraduate Scholarships and Seed-funding available for projects across four themes

[email protected]

The University of Sydney Page 21 TEAM –Prof Sharon Naismith Head, Neuropsychologist –Prof Ian Hickie Psychiatrist –Prof Simon Lewis Neurologist –Prof Jim Lagopoulos Neuroimaging –Prof Ron Grunstein Sleep physician –Ms Amelia English Clinical Trials Manager Acknowledgements –Dr Shantel Duffy Postdoctoral Researcher –Dr Loren Mowzsowski Neuropsychologist –Dr Haley LaMonica Neuropsychologist –Dr Zoe Terpening Neuropsychologist –Dr Keri Diamond Neuropsychologist –Dr Rebekah Ahmed Neurologist –Dr Jerome Ip Geriatrician/Neurologist –Ms Tess Anderson Trials Nurse FUNDING –Ms Stacey West Research Assistant –NHMRC PRACTITIONER FELLOWSHIP (LEWIS) –Ms Keshani Jayaweera PhD student –NHMRC ‘NEUROSLEEP’ CRE (GRUNSTEIN) –Mr Nathan Cross PhD student –NHMRC PROJECT GRANT (NAISMITH) –ALZHEIMERS –ANZ TRUSTEES (MASON FOUNDATION)

–PARKINSON’S NSW –BEYOND BLUE NEUROSLEEP –NHMRC/ARC Dementia Fellowship Scheme NHMRC Centre of Research Excellence

– Healthy Brain, Healthy Sleep

– Postdoctoral Fellowships, Postgraduate Scholarships and Seed-funding available for projects across four themes

[email protected]

The University of Sydney Page 22