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 disordersSleep

disorders

Sensory disorders

Neuropsychiatric disorders

e.g. psychosis, depression, anxiety

and dementia

Barraud Q, et al. Exp Neurol 2009;219:574-82.

Significant changes in sleep pattern in MPTP-treated monkeys

Chaudhuri KR, et al. Mov Disord 2006;21:916-23 .

Significantly higher proportion of NMS in patients versus controls

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

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

Correlation with age and disease duration (odds ratio)

Symptom Male (N=2076)

Female(N=1338)

Sexa Ageb Disease durationb

Orthostatic hypotension

10% 11% NS 1.03 (1.02-1.05)

1.02 (1.00-1.05)

Urinary incontinence 21% 22% NS 1.04 (1.03-1.05)

1.04 (1.02-1.05)

Sexual dysfunction 30% 8% 0.09 (0.06-0.12)

1.02 (1.01-1.03)

NS

Erectile dysfunction 50% 1.04 (1.02-1.05)

NS

Sleep disturbance 35% 43% 1.42 (1.23-1.64)

NS 1.03 (1.02-1.04)

aOdds <1 is equivalent to decreased risk for women

bIncrease 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

Chaudhuri KR,et al. Mov Disord 2010;25:704-9.

Most common non-declared NMS (N=242)

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

Tot

al s

core

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 problems 51.5

Sleep disturbance 43.6

Anxiety 38.7

Urinary problems 32.5

Memory/confusion 31.3

Bowel problems 31.3

Dribbling of saliva 29.4

Speech problems 27.6

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;73:1584-91.

NMS correlate with deteriorating quality of life

Spearman R = 0.70

NMSS-Study 1 PDQ-8 NMSS-Study 2 PDQ-39 EQ-5D

N = 242 N = 411

Age - 0.03 Age 0.05 - 0.13

PD duration 0.26 PD duration 0.34 - 0.33

H & Y staging 0.41 H & Y staging 0.51 - 0.53

UPDRS-3 0.46 SCOPA-Motor exam 0.47 - 0.59

UPDRS-4 0.36 SCOPA-Motor complications

0.53 - 0.47

FAB-Total - 0.39 SCOPA-Cognition - 0.41 0.34

NMS Scale 0.70 NMS-Scale 0.70 - 0.57

NMS Quest 0.63 SCOPA-Autonomic 0.61 - 0.49

Fatigue-VAS - 0.40 PDSS - 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

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.

Intervention Efficacy* Likely efficacy

Unlikely efficacy

Insufficient evidence No efficacy

Surgery STN-DBS

Unilateral pallidotomy

Bilateral pallidotomy

Unilateral thalamotomy

Pallidal stimulation

Unilateral thalamic DBS

Foetal transplantation

Levodopa Conversion from standard to slow release

Dopamine agonist

Pramipexole

Cabergoline

MOA-B inhibitors

Rasagiline Selegiline

COMT-inhibitors TolcaponeEntacapone

Anticholinergics All

Amantadine 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;16:218-21.

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

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