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

2. 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

3. Barraud Q, et al. Exp Neurol 2009;219:574-82. Significant changes in sleep pattern in MPTP-treated monkeys

4. Chaudhuri KR, et al. Mov Disord 2006;21:916-23. Significantly higher proportion of NMS in patients versus controls

5. Martinez-Martin P, et al. Mov Disord 2007;22:1623-9. Chaudhuri KR, et al. Mov Disord 2006;21:916-23. 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

6. Barone P, et al. Mov Disord 2009;24:1641-49. 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

7. 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 (1.02-1.05) 1.02 (1.00-1.05) Urinary incontinence21%22%NS1.04 (1.03-1.05) 1.04 (1.02-1.05) Sexual dysfunction30%8%0.09 (0.06-0.12) 1.02 (1.01-1.03) NS Erectile dysfunction50%1.04 (1.02-1.05) NS Sleep disturbance35%43%1.42 (1.23-1.64) NS1.03 (1.02-1.04) 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;14:1405-8. 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

8. Chaudhuri KR,et al. Mov Disord 2010;25:704-9. Most common non-declared NMS (N=242)

9. Honig H,et al. Mov Disord 2009;24:1468-74. 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

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

11. 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.

12. 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

13. Quality of life This educational material has been supported by Abbott

14. 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.

15. 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;73:1584-91. NMS correlate with deteriorating quality of life Spearman R = 0.70

16. NMSS-Study 1PDQ-8NMSS-Study 2PDQ-39EQ-5D N = 242N = 411 Age- 0.03Age 0.05- 0.13 PD duration 0.26PD duration 0.34- 0.33 H & Y staging 0.41H & Y staging 0.51- 0.53 UPDRS-3 0.46SCOPA-Motor exam 0.47- 0.59 UPDRS-4 0.36SCOPA-Motor complications 0.53- 0.47 FAB-Total- 0.39SCOPA-Cognition- 0.41 0.34 NMS Scale 0.70NMS-Scale 0.70- 0.57 NMS Quest 0.63SCOPA-Autonomic 0.61- 0.49 Fatigue-VAS- 0.40PDSS- 0.49 0.41 Martinez-Martin P, et al. Mov Disord 2007;22:1623-9. Martinez-Martin P, et al. Neurology 2009;73:1584-91. NMSS score correlates strongest with quality of life in 2 independent studies

17. Martinez-Martin P, Deuschl G. Mov Disord 2007;22(6):757-765.. 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

18. Long-term effect of duodenal carbidopa/ levodopa gel infusion: Improvement in quality of life Puente V, et al. Parkinsonism Relat Disord 2010;16:218-21.

19. Deuschl G, et al. A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease. New England Journal of Medicine Vol. 355, No, 9 2006, p896- 908. Copyright © 2006 Massachusetts Medical Society. All rights reserved. Randomized trial of deep brain stimulation for Parkinson’s disease

20. 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