Results

Non-motor symptoms in early drug-naïve Parkinson’s disease

Rui Liu1, David M. Umbach2, Shyamal D. Peddada2, Zongli Xu1, Alexander I. Tröster3, Xuemei Huang4, Honglei Chen1

1.Epidemiology Branch and 2.Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC. 3.Barrow Neurological Institute, Phoenix, AZ. 4.Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.

PD cases performed substantially worse than controls on nearly all NMS measurements

Male and female PD patients were comparable on motor presentations

Notable sex differences observed for several non-motor features: o Male PD patients experienced more pronounced

deficits in olfaction and several cognitive domains o Female cases had much higher trait anxiety

Similar but smaller sex differences in cognition among controls

A few of these NMS, sense of smell in particular, could effectively differentiate newly diagnosed PD cases from controls o Previous data suggest that the loss of the sense of

smell is among the earliest NMS for PD o Potential predictive values of these symptoms should

be further investigated in longitudinal studies of individual without PD

Conclusions

Parkinson’s disease (PD) patients suffer from a wide array of non-motor symptoms (NMS)

o Prevalent and difficult to treat o Related to poor quality of life, higher morbidity

and mortality

Some NMS may precede PD clinical diagnosis

o May help early case identification and differential diagnosis

Previous data suggest sex difference in PD incidence and possibly progression and risk factors

o No studies look into potential gender differences of NMS in newly diagnosed, untreated PD patients

Introduction

To examine potential sex differences in the presence of NMS in de novo PD patients

Identify patterns of NMS that can best differentiate early PD cases from controls

Objectives

Quantile regression model to assess potential sex-

differences in NMS among PD patients and controls

Stepwise logistic regression and receiver operating characteristic (ROC) to identify NMS that can best differentiate de novo PD cases from controls

All analyses stratified by gender

Statistical Analyses

The Parkinson’s Progression Markers Initiative (PPMI) study

o 414 de novo, drug-naïve PD patients: • Asymmetric resting tremor or asymmetric

bradykinesia • Diagnosed within two years • Hoehn and Yahr stage I or II • Age 30 years or older at diagnosis • Evidence of dopamine transporter deficit • Untreated for PD

o 188 healthy controls: • Free of neurological disorder • No first-degree relative with PD • No evidence of dopamine transporter deficit • MoCA score >26

NMS assessments

o 12 validated tests and structured questionnaires to examine 5 major areas of non-motor feature: sleep, olfaction, neurobehavioral and autonomic disturbances, and cognitive domains

Methods

PD Patients Healthy Controls

Male (n=269)

Female (n=145)

P a

Male (n=121)

Female (n=67)

P a

Pinteraction

Sleep Disorder Epworth sleepiness scale 6 (3-8) 5 (3-8) 0.4 5 (3-8) 5 (3-7) 0.7 0.95

RBDSQ 4 (2-6) 3 (2-5) 0.2 2 (1-4) 2 (1-4) 1.0 0.39

Olfactory

UPSIT 22 (15-28) 24 (19-31) 0.02 35 (32-37) 36 (34-38) 0.3 0.45 Neurobehavioral

Total anxiety 60 (50-75) 64 (53-76) 0.1 52 (46-64) 54 (45-69) 0.4 0.81

State anxiety 31 (24-38) 31 (25-40) 1.0 25 (21-33) 26 (21-33) 0.9 1.00

Trait anxiety 29 (25-36) 32 (27-40) 0.02 26 (24-32) 29 (23-35) 0.5 0.50

Geriatric depression 2 (1-3) 2 (1-3) 1.0 1 (0-1) 1 (0-2) 1.0 1.00

Cognitive Domains

Global 27 (26-29) 28 (26-29) 0.0008 28 (27-29) 28 (27-29) 0.5 0.06

Memory 46 (41-52) 51 (43-56) 0.0003 50 (43-55) 54 (48-57) 0.0007 0.83

Visuospatial 60 (55-67) 56 (47-61) <.0001 61 (56-67) 56 (50-62) 0.002 0.80 Working Memory-Executive 53 (48-58) 53 (49-57) 0.7 53 (49-58) 54 (50-60) 0.4 0.73

Attention-Processing Speed 45 (39-49) 47 (41-52) 0.3 49 (43-55) 52 (45-58) 0.04 0.27

Autonomic

SCOPA-AUT 8 (5-12) 9 (6-12) 0.2 5 (3-7) 6 (4-9) 0.002 0.16

a Based on quantile regression adjusted for age and education; P for interactions are between sex and enrollment-category.

Table 2. Medians and interquartile range of NMS scores by sex in patients and controls

A. Men B. Women

Significant NMSa

predictors

Regression coefficient

Standard error

P

UPSIT -3.097 0.49 <.0001 RBDSQ 0.646 0.25 0.01 MoCA -0.582 0.28 0.04 a All NMS variables were standardized to z-scores.

Table 1. Demographic and clinical characteristics

PD Patients

Male (n=269)

Female (n=145)

P a

Age, y 62 61 0.1

Race (% white) 94 92 0.6

Education, y 16 15 0.2

Disease duration, mo 6 7 0.5

Tremor at diagnosis, (%) 78 78 1.0

Rigidity at diagnosis, (%) 80 69 0.01

Bradykinesia at diagnosis, (%) 84 81 0.5

Postural instability at diagnosis, (%)

7 7 0.9

Family history of PD, (%) 15 10 0.1

UPDRS Part III score 21 20 0.6

Hoehn and Yahr stage, median 2 2 0.8

Healthy Controls

Male (n=121)

Female (n=67)

P

Age, y 62 60 0.2

Race (% white) 95 93 0.4

Education, y 16 15 0.1 a Based on Mann-Whitney U test.

Figure 1. Receiver operating characteristic (ROC) curves with area under the ROC curve (AUC) of NMS assessments for men (A) and women (B)

AUC=0.919 (95% CI: 0.89-0.95) AUC=0.903 (95% CI: 0.86-0.95)

Significant NMSa

predictors

Regression coefficient

Standard error

P

UPSIT -2.353 0.29 <.0001 SCOPA-AUT 1.059 0.28 0.0001 MoCA -0.536 0.23 0.022 a All NMS variables were standardized to z-scores.