Sleep and Parkinson’s Disease Prof. Sebastiaan Overeem, MD, PhD Sleep Medicine Center ‘Kempenhaeghe’, Heeze, NL Eindhoven University of Technology, NL

Disclaimer Goal: give a broad overview of sleep in Parkinson’s Disease (PD) Broad view of the mechanisms and symptoms of sleep disorders Some general example of specific disorders and possible treatments NOT medical advice Discuss any sleep problems with your physician, PD nurse, etc. Relatively short overview; most important: interactive discussion 2

Sleep

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Sleep is an active and very complex brain process 5

Sleep is an active and very complex brain process 6

So.. plenty of reasons for things to go wrong.. We sleep 1/3 of our lives Sleep regulated by many different brain regions Sleep disorders are very prevalent More than 10% of the population Extensive spectrum of different sleep disorders 7

Parkinson’s Disease (PD)

PD is (much) more than just a movement disorder Besides the motor symptoms tremor rigidity posture and balance problems Spectrum of non-motor symptoms Psychiatric (e.g. depression) Urologic Sexual Memory Hypersalivation Sleep disorders! 9

Sleep disorders in PD 10

Sleep versus other non-motor symptoms nocturia 59.5% urinary urgency 53.6% constipation 50.2% mood disorders 48.2% insomnia 44.3% concentration 44.0% anxiety 43.4% memory 43.1% restlessness 40.3% dribbling 40.1% REM Sleep Behavior Disorder 34.0% Excessive Daytime Sleepiness 30.0% Clayton et al Park & Rel Dis 2006 11

Sleep versus other non-motor symptoms nocturia 59.5% urinary urgency 53.6% constipation 50.2% mood disorders 48.2% insomnia 44.3% concentration 44.0% anxiety 43.4% memory 43.1% restlessness 40.3% dribbling 40.1% REM Sleep Behavior Disorder 34.0% Excessive Daytime Sleepiness 30.0% Clayton et al Park & Rel Dis 2006 12

Sleep disorders in PD How often do sleep disorders occur in PD? Very much depends on the definition Very much depends on the diagnostic method 60 - >90% has some disruption/disorder of sleep (!) 13

Reduced quality of life; also for partners! 14

Sleep disorders in PD Many different sleep disorders / sleep symptoms Difficulties initiating sleep Difficulties maintaining sleep Sleep related movement disorders Etc Complex (and often combined) causes Damage to sleep regulating brain areas Secondary to (motor) symptoms Medication side-effects 15

Secondary to PD symptoms Tremor Rigidity Akinesia / bradykinesia Cramps Pain Nocturia … 16

Damage to sleep related brain regions REM sleep behaviour disorder Insomnia Restless legs Hallucinations Sleep related breathing disorders Sleep related stridor Excessive daytime sleepiness 17

Medication related Too short acting PD medication (‘nocturnal off’) Hyperkinesias at night Insomnia Hallucinations Excessive daytime sleepiness (dopamine agonists) 18

Examples

Excessive daytime sleepiness 15-50% of people with PD All kinds of situations ‘Sleep attacks’ due to dopamine agonists Often secondary to disturbed nocturnal sleep Sometimes secondary to depression 20

Sleep disruption secondary to motor symptoms Tremor, muscle/joint paints Difficulties turning around in bed! When this is not possible anymore; then it becomes clear how important it is to have a comfortable sleep position 21

Sleep problems due to motor symptoms Difficulties turning around in bed Degree of sleep disruption Never Seldom Regularly Most of the time Always 5 6 7 8 9 10 Maartje Louter et al JAGS (2012) 22

Sleep disorders due to the PD disease process 23

Muscle activity during REM sleep During dreaming sleep (REM sleep): complete muscle paralysis This is actively regulated by the brain, from the brainstem This exact region is affected very early in the PD disease process 24

REM sleep behavior disorder (RBD) What if the muscle weakness during REM sleep does not occur? This would result in ‘dream enactment’ RBD present in more than 60% of PD patients 25

Treatment

Treatment of sleep disorders in PD Sometimes: easy to treat Often, it can be a complex situation Crucial (in my view) Attention to sleep by every PD caregiver Sleep’interview’ in every PD patient Help from a sleep medicine specialist can be very helpful Dedicated PD-sleep clinic at Kempenhaeghe sleep center 27

Treatment of sleep disorders in PD Sometimes: easy to treat Often, it can be a complex situation Crucial (in my view) Attention to sleep by every PD caregiver Sleep’interview’ in every PD patient Help from a sleep medicine specialist can be very helpful Dedicated PD-sleep clinic at Kempenhaeghe sleep center  treatment start with a precise sleep diagnosis 28

General aspects: good sleep ‘hygiene’ Regular bedtimes Comfortable bed and bedroom Do not spend too long in bed Mind stimulants (caffeine, strenuous exercise before bedtime..) Do not sleep too long during the day Etc. 29

Treatment: medication review Always important to critically review all medication Increase ‘dopaminergic control’ at night Reduce or stop ‘sleep offending’ medication 30

Examples of specific treatments Nocturia: behavioural, catheter, medication Insomnia: medication changes, behavioural treatment, medication REM Sleep Behavior Disorder: medication Restless Legs: iron, specific medication Excessive Daytime Sleepiness: medication changes, stimulants 31

Examples of specific treatments Nocturia: behavioural, catheter, medication Insomnia: medication changes, behavioural treatment, medication REM Sleep Behavior Disorder: medication Restless Legs: iron, specific medication Excessive Daytime Sleepiness: medication changes, stimulants  Can be difficult  Sometimes ‘trial & error’, but do not give up!  Interaction between PD neurologist and sleep medicine specialist! 32

Sleep as an ally

Sleep benefit in PD Sleep benefit: temporary improvement in motor function after sleep Unexpected after night without medication Sometimes after daytime naps Merel van Gilst et al JAGS (2012) 34

Sleep benefit in PD Merel van Gilst et al PRD (2013) 35

Sleep benefit in PD Mainly based on subjective reports Objective measurements in clinic: no clear picture Current research in our group: automated video analysis at home Merel van Gilst et al PRD (2013) + SLEEP (2015) 36

Conclusions

Conclusions Sleep disorders are very prevalent in PD Complex causes, often several factors together Treatable, given a precise sleep diagnosis Interaction with sleep medicine specialist can be helpful  attention to sleep by all PD caregivers! 38