32 sleep in neurodegeneration ismc 2021 · the clinical presentation can be different and masked by...
TRANSCRIPT
Biography
Dr Kirstie Anderson
Consultant Neurologist and Honorary Senior Lecturer
Dr Anderson, Consultant Neurologist and Honorary Senior Lecturer, works within one of the UK’s
largest sleep services in Newcastle and explores the links between sleep, mental health and
neurodegeneration within her research in Newcastle University. She was the clinical lead developing
the online insomnia programme Sleepstation, now available within the NHS. As one of the few UK
neurologists to specialise in sleep, she sees and treats paediatric and adult sleep disorders, has
published widely on sleep disorders and lectures regionally and nationally. She is current president
of the Sleep Medicine section of the Royal Society of Medicine and runs annual sleep training days in
Newcastle.
Abstract
The lecture will provide an understanding of the role of sleep and sleep disorders in
neurodegeneration. Firstly it is necessary to understand the normal changes in sleep with ageing.
Next the talk will cover the primary sleep disorders which are common in those over the age of 65.
The clinical presentation can be different and masked by other medical comorbidities. Certain sleep
disorders and in particular REM sleep behaviour disorder can predict subsequent neurodegenerative
disorders and finally an approach to the management of poor sleep in the neurodegenerative
disorders will be covered including common clinical scenarios.
Learning objectives
1, To understand sleep physiology during normal ageing
2. To understand the common primary sleep disorder and approach to diagnosis in those with
neurodegenerative conditions
3. To understand the pattern of sleep disturbance in neurodegeneration and parkinson’s disease in
particular and an approach to treatment alongside common clinical scenarios
References
Li J, Vitiello MV, Gooneratne NS. Sleep in Normal Aging. Sleep Med Clin. 2018 Mar;13(1):1‐11. doi:
10.1016/j.jsmc.2017.09.001.
Wilson S, Anderson K, Baldwin D, et al. British Association for Psychopharmacology consensus
statement on evidence‐based treatment of insomnia, parasomnias and circadian rhythm disorders:
An update. J Psychopharmacol. 2019 Aug;33(8):923‐947. doi: 10.1177/0269881119855343.
Postuma RB, Iranzo A, Hu M, et al. Risk and predictors of dementia and parkinsonism in idiopathic
REM sleep behaviour disorder: a multicentre study. Brain. 2019 Mar 1;142(3):744‐759. doi:
10.1093/brain/awz030
Louter M, Aarden WC, Lion J, Bloem BR, Overeem S. Recognition and diagnosis of sleep disorders in
Parkinson's disease. J Neurol. 2012 Oct;259(10):2031‐40. doi: 10.1007/s00415‐012‐6505‐7.
Leng Y, Musiek ES, Hu K, Cappuccio FP, Yaffe K. Association between circadian rhythms and
neurodegenerative diseases. Lancet Neurol. 2019 Mar;18(3):307‐318. doi: 10.1016/S1474‐
4422(18)30461‐7.
32 Anderson Sleep and neurodegeneration
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Sleep and neurodegeneration“the past is a foreign country, they do things differently there”
1. Sleep and circadian rhythm in ageing
2. Primary sleep disorders in the elderly
3. Sleep disturbance within neurodegeneration
..
Van Cauter et al. JAMA 2000
SWS
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The Ageing HoursAge 35
Age 75
The Ageing Clocks
Decreased circadian amplitude
Phase advance by 30 minutes a decade
Decreased ability to tolerate phase shift declines eg shift work, jet lag
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Ageing Glymphatics – is bad sleep neurotoxic
The glymphatic system – waste clearance system for the mammalian central nervous system – clearance of the interstitial fluid and extracellular fluids. Facilitated by aquaporin water channels
“Sleep drives metabolic clearance from the adult brain” Science 2013 Xie et al. with a 60% increase in the interstitial fluid space during sleep
Increased rate of B amyloid clearance –therefore sleep to remove potentially neurotoxic waste products.
In-vivo two photon imaging using small fluorescent tracers
Illiff and Needergard2012
Measuring sleep in ageing
Actigraphy 65yr olds
Objective versus subjective sleep complaintsMrOS recruited from 2003-2005, Home PSG 2,601 at baseline. Wrist actigraphy , AMT6s and self report. Average follow up 3.5 yearsMultiple analyses but…fragmented sleep and objectively reduced TST predicts cognitive decline, depression but does not correlate with self report EDS or PSQI. Lower nocturnal melatonin predicts worse EDS and poorer night sleep
1. Blackwell T et al. Sleep 20142. Song Y et al. Sleep 20153. Smagula SF et al. Am J Psychiatry 2015
The Newcastle 85+ cohort study (421 patients)Anderson KN et al. Age and Ageing 2014PSQI ESS useless
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Summary
Objective evidence of impaired sleep homeostat and circadian rhythm (the hours and the clocks) with greatest changes from early 30s to 60s
Decrease in TST by approx. 30 minutes a decade from middle age with marked decline in percentage of slow wave sleep
In elderly subjective complaints highly variable and daytime naps not clearly correlated with objective sleepiness
Other medical comorbidities correlate with worse sleep. Sleep disruption for any reason is associated with increased mortality and morbidity and impaired cognition.
Bad sleep is neurotoxic – whatever the reason
Primary sleep disorders in ageing
Up to 50% of older adults complain of significant chronic sleep disturbance (Foley et al. 1995)
• Obstructive sleep apnoea 10% of men over 40, 5% of women• Restless legs syndrome 5%• Parasomnia 2-3 %• Insomnia 5%• Circadian Rhythm Disorder
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Take A Sleep History• Snoring +/- witnessed apnoeas, neck circ > 17, increased BP (STOPbang)• Restless legs ? – duvet off, hot feet, PLMS (15-30 secs for most)• “Take me through a typical 24 hours”• “Are you out of the house every day?”• Daytime napping versus fatigue – partner history where possible• For insomnia – typically a low Epworth Sleepiness Score (beware the three R’s –
RLS, reflux, rhythm)• Epworth Sleepiness Score (added value when also from spouse)
• The rest of the prescription• Uppers -nasal decongestants, OTC painkillers, betahistine, inhalers• Downers – opioids, pregabilin, gabapentin, amitriptyline• Caffeine – count the cups, nicotine and alcohol
Obstructive sleep apnoea in older adults
10-20% prevalence in >65
May present atypically (lower BMI, “insomnia”, falls, cognitive impairment)Evidence for CPAP improving attention, cognition, decreasing falls and cardiovascular outcomeCPAP effective at all ages when symptomatic including those over 75Therefore screen if symptomatic sleepiness in all with treatment resistant hypertension, AF, diabetes, vascular events (STOPbang)Treatment - Effect on cognition in the well elderly not proven to date with RCTDriving safety – the past predicts the future – ask about crashes/near misses. 5-7X increased risk of serious crash with untreated OSA
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Restless Legs SyndromeAt least 10% of sleep disturbed PD, 30% of diabetics, co-existent sleep apnoea. Increased age a risk factor. Typically variable but progressive over the years when severe.The best diagnostic test – ask the patient!
Lifestyle first –nicotine/caffeine/alcohol/ferritin replacement if below 75, ?aggravating medications
Dopamine agonists, Ropinirole, Pramipexole, Rotigotine patch – all licensed but. 5-11% ICD at least and augmentation over time in 50-70%
•Pregabilin/Gabapentin but evening only•Not melatonin/amitriptyline/mirtazepine•(IV iron – RCT mixed results – helpful for some who can’t tolerate other treatments)
Insomnia Disorder in neurodegeneration
“How do people go to sleep? I'm afraid I've lost the knack.” ― Dorothy Parker
If no trouble falling asleep – consider OSA
Difficulty falling asleep but not staying asleep, consider RLS
First line treatment CBTi – greater evidence for exercise in older adults
Increased risk of falls with hypnotics in the elderly (Xu and Anderson ACNR, 2018).
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“The sleep becomes much disturbed”
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Sleep disturbance in Parkinsonian disorders
• Common, early non-motor symptom. 90-100% in advanced.
• Daytime sleepiness, distinct from sleep attacks (which are uncommon)
• Insomnia – often with night pain and bradykinesia
• RBD and vivid dreams (severe and early in multiple system atrophy)
• Nocturia
• Restless legs
• Sialorrhoea
Sleep and Parkinson’s Disease
ICICLE-PD 159 PD patients at diagnosis assessed every 18monthsSleep sub study – 110 patients and 97 controls.
No correlation between PSQI/ESS/Oximetry. Increased PLMS but not symptomatic RLSPD had more daytime naps but didn’t rate themselves sleepier
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RBD and Parkinson’s disease• The most robust non-motor prodromal
symptom to date. A predictor of early cognitive impairment and visual hallucinations
• 50% of those within a PD clinic, 50% of those with RBD will develop a neurodegenerative problem within 5 years. 91% at 15 years, 70% will have injury
• Normal velocity movements retained in even advanced PD but loss of dream recall common with cognitive impairment
• 10% get better and not all need treatment
Is RBD ever really idiopathic ?
•Postmortem studies suggest lewy body pathology
•50% of patients with confirmed idiopathic RBD have mild cognitive impairment
•DAT scans do progress and predict neurodegeneration (for review of brain imaging findings. Heller et al. Sleep Med Rev. 2016)
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Approach to poor sleep in Parkinson’s disease
Snoring apnoeas (stridor – MSA) drugs (timing, dose), typical 24 hours with sleep diaries if possible, ESS, STOPbang
RBD +/- self injury at night, or partner injury
Nocturia,
Restless legs or restless head (insomnia) ?
Depression – 20% have hypersomnia not EMW, limited evidence for tricyclics, SNRI over SSRI
Sialorrhoea – anticholinergics, clonidine, botox
Modafinil – mixed results from RCTs, headache common, dose range 100-400mg
Cholinesterase inhibitors alerting, may improve RBD
Sialorrhoea – anticholinergics, clonidine, botox
For a flow chart – Louter et al. Journal of Neurology 2012
Can sleep predict which neurodegeneration?
•With questionnaires alone ?
•Primary sleep disorders common in all groups
•RBD the strongest marker for PDD/DLB
•Daytime / fluctuating more common in PDD/DLB
•Sleep apnoea in vascular dementia (VaD)
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Common clinical questions• Q. Sleepy - Do I stop the dopamine agonist? Or switch to an even more expensive
drug?• A. sleepiness commonest at initiation and often wears off, long acting agonists some
benefit improving sleep• Q. Do they need a full sleep study? And will it change the diagnosis• A. Often not, except possibly young onset PD or possible MSA, or research trials but
screen for sleep apnoea more than you are doing• Q. Driving?• A.near misses, claims, accidents at the wheel in the last 12 months? ESS > 17• symptomatic sleepiness due to obstructive sleep apnoea is notifiable to DVLA and
most car insurers, PD notifiable and daytime sleepiness specifically mentioned. • Dementia and driving – history from spouse, issues are multifactorial and need
regular review but “are you still happy for grandad (or grandma) to drive the grandchildren?” my most useful question. ESS from relative as well as patient. Self report sleepiness less useful in those with cognitive impairment.
• Consider driving assessment at your local rehab centre (UK - typically free or low cost)
Summary• Sleep and circadian rhythm disturbance are a biomarker for a badly ageing
brain?• Primary sleep disorders are common and treatable – take a sleep history in all
those with cognitive impairment. Do you go outside every day? Sleep apnoea10%.
• REM sleep behaviour disorder – the most robust predictor of a neurodegeneration. With careful screening 50% have MCI at diagnosis. RCTs still awaited but melatonin has the best safety profile of the current therapies. Ongoing functional imaging research to predict those at high risk of conversion
• Sleep disturbance in PD is multifactorial, nocturia, night bradykinesia, daytime sleepiness, depression (RBD and sleep attacks). So take a history.
• Bright light, physical activity, regular schedules for all