title: Postural instability and gait are associated with severity and prognosis of Parkinson disease.
abstract: Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)-dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications.
  
  
  
  Linear mixed models were applied to data from the Profiling Parkinson's disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson's disease [SCOPA]-Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA-Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA-Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365).
  
  
  
  The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results.
  
  
  
  In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself.
authors.affiliation: From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain. j.f.van_der_heeden@lumc.nl.
authors.forename: Jorine F
authors.initials: JF
authors.lastname: van der Heeden
authors.affiliation: From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain.
authors.forename: Johan
authors.initials: J
authors.lastname: Marinus
authors.affiliation: From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Martin
authors.affiliation: From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez-Blazquez
authors.affiliation: From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Geraedts
authors.affiliation: From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain.
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
mesh_terms: D000368:Aged; D060825:Cognitive Dysfunction / Q000150:complications / Q000503:physiopathology; D003863:Depression / Q000150:complications / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005684:Gait / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D004856:Postural Balance / Q000187:drug effects; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications / Q000503:physiopathology; D012720:Severity of Illness Index; D014202:Tremor / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology