Potential sex differences in nonmotor symptoms in early drug-naive Parkinson disease.
OBJECTIVE
To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls.


METHODS
Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains.


RESULTS
Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures-University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory-effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89-0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI: 0.89-0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI: 0.86-0.95).


CONCLUSIONS
Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls.
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA. liur2@niehs.nih.gov.
Rui
R
Liu
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.
David M
DM
Umbach
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.
Shyamal D
SD
Peddada
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.
Zongli
Z
Xu
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.
Alexander I
AI
Tröster
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.
Xuemei
X
Huang
From the Epidemiology Branch (R.L., Z.X., H.C.) and Biostatistics and Computational Biology Branch (D.M.U., S.D.P.) of the National Institute of Environmental Health Sciences, Research Triangle Park, NC; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; Department of Neurology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA.
Honglei
H
Chen
D000368:Aged; D001007:Anxiety / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000857:Olfaction Disorders / Q000209:etiology*; D010300:Parkinson Disease / Q000150:complications* / Q000175:diagnosis*; D012737:Sex Factors; D012893:Sleep Wake Disorders / Q000209:etiology*