Non-motor symptoms of Parkinson’s disease This educational material has been supported by Abbott

Adler CH. Mov Disord 2005;20(Suppl 11):S23-9. Non-motor symptoms of Parkinson’s disease: Patient burden Non-motor symptoms (NMS) Autonomic dysfunction Gastrointestinal disorders Orthostatic hypotension Urologic disorders Sleep disorders Sensory disorders Neuropsychiatric disorders e.g. psychosis, depression, anxiety and dementia

Barraud Q, et al. Exp Neurol 2009;219: Significant changes in sleep pattern in MPTP-treated monkeys

Chaudhuri KR, et al. Mov Disord 2006;21: Significantly higher proportion of NMS in patients versus controls

Martinez-Martin P, et al. Mov Disord 2007;22: Chaudhuri KR, et al. Mov Disord 2006;21: In a recent global study, nocturia was identified as the most prevalent non-motor symptom in patients with Parkinson’s disease Higher prevalence and wider range of NMS in Parkinson’s disease

Barone P, et al. Mov Disord 2009;24: Copyright (2009 Movement Disorder Society); Reproduced with permission of John Wiley & Sons, Inc. Non-motor symptoms common across all stages of Parkinson’s disease Prevalence of NMS according to Parkinson’s disease status

Correlation with age and disease duration (odds ratio) SymptomMale (N=2076) Female (N=1338) Sex a Age b Disease duration b Orthostatic hypotension 10%11%NS1.03 ( ) 1.02 ( ) Urinary incontinence21%22%NS1.04 ( ) 1.04 ( ) Sexual dysfunction30%8%0.09 ( ) 1.02 ( ) NS Erectile dysfunction50%1.04 ( ) NS Sleep disturbance35%43%1.42 ( ) NS1.03 ( ) a Odds <1 is equivalent to decreased risk for women b Increase of risk for 1 year of age or disease duration NS = non-significant Wullner U,, et al, et al. Eur J Neurol 2007;14: Logistic regression analysis revealed a significant correlation of orthostatic hypotension and urinary incontinence with age and disease duration NMS in Parkinson’s disease: Association with gender age and disease duration

Chaudhuri KR,et al. Mov Disord 2010;25: Most common non-declared NMS (N=242)

Honig H,et al. Mov Disord 2009;24: The proportion of patients with advanced Parkinson’s disease with improving health status and improving quality of life as measured by sleep, NMSS and PDQ-8 Effects of duodenal carbidopa/levodopa gel infusion on NMS

Total score Naidu Y,et al. Mov Disord 2009;24(Suppl1):S360. Effect of apomorphine on NMS

Continuous apomorphine infusion improves NMS Non-motor symptom improvement driven by improvement in sleep, mood, urinary, gastrointestinal and miscellaneous domains Martinez-Martin P,et al. Mov Disord Society Meeting 2010.

Non-motor symptoms are highly prevalent in Parkinson’s disease and are associated with poor quality of life In a recent global study, the most common non-motor symptoms were nocturia, urinary urgency, and constipation Non-declaration of non-motor symptoms is common in Parkinson’s disease, the most frequently non-declared symptoms were delusions and day-time sleepiness Preliminary studies indicate the potential for alleviation of non- motor symptoms and associated improvements in quality of life with continuous dopaminergic stimulation Summary

Quality of life This educational material has been supported by Abbott

NMS are a major cause of poor quality of life in Parkinson’s disease Non-motor symptom% of patients (N=163) Balance problems51.5 Sleep disturbance43.6 Anxiety38.7 Urinary problems32.5 Memory/confusion31.3 Bowel problems31.3 Dribbling of saliva29.4 Speech problems27.6 The most prevalent non-motor symptoms causing impairment of quality of life among patients aged 33 to 90 years Adapted from Gulati A et al. Mov Disord 2004;19(Suppl 9):S403.

NMS Scale and PDQ-39 Load of non- motor symptoms shows robust correlation with deteriorating quality of life Martinez-Martin P, et al. Neurology 2009;73: NMS correlate with deteriorating quality of life Spearman R = 0.70

NMSS-Study 1PDQ-8NMSS-Study 2PDQ-39EQ-5D N = 242N = 411 Age- 0.03Age PD duration 0.26PD duration H & Y staging 0.41H & Y staging UPDRS SCOPA-Motor exam UPDRS SCOPA-Motor complications FAB-Total- 0.39SCOPA-Cognition NMS Scale 0.70NMS-Scale NMS Quest 0.63SCOPA-Autonomic Fatigue-VAS- 0.40PDSS Martinez-Martin P, et al. Mov Disord 2007;22: Martinez-Martin P, et al. Neurology 2009;73: NMSS score correlates strongest with quality of life in 2 independent studies

Martinez-Martin P, Deuschl G. Mov Disord 2007;22(6): Copyright (2007 Movement Disorder Society); Reproduced with permission of John Wiley & Sons, Inc. InterventionEfficacy*Likely efficacy Unlikely efficacy Insufficient evidenceNo efficacy SurgerySTN-DBS Unilateral pallidotomy Bilateral pallidotomy Unilateral thalamotomy Pallidal stimulation Unilateral thalamic DBS Foetal transplantation LevodopaConversion from standard to slow release Dopamine agonist Pramipexole Cabergoline MOA-B inhibitors RasagilineSelegiline COMT- inhibitors Tolcapone Entacapone AnticholinergicsAll Amantadine *Evidence of positive effect on health related quality of life based on at least one high-quality RCT and no conflicting data from other RCTs. Evidence based on motor improvements. Efficacy of interventions on health-related quality of life

Long-term effect of duodenal carbidopa/ levodopa gel infusion: Improvement in quality of life Puente V, et al. Parkinsonism Relat Disord 2010;16:

Deuschl G, et al. A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease. New England Journal of Medicine Vol. 355, No, , p Copyright © 2006 Massachusetts Medical Society. All rights reserved. Randomized trial of deep brain stimulation for Parkinson’s disease

Summary Non-motor symptoms have a major impact on quality of life in patients with Parkinson’s disease Long-term duodenal carbidopa/levodopa gel infusion treatment alleviates many of the non-motor symptoms with a resultant improvement in quality of life Long-term DBS also has a significant impact on non-motor symptoms with an associated improvement in quality of life