title: The influence of age and approaching death on the course of nondopaminergic symptoms in Parkinson's disease.
abstract: BACKGROUND
  The influence of approaching death in addition to age and their interaction on the course of a broad spectrum of nondopaminergic features in Parkinson's disease (PD) has not been well studied. This study addresses this issue in a prospectively designed study.
  
  
  METHODS
  During five years, the severity of axial symptoms, cognitive impairment, psychotic symptoms, autonomic dysfunction, depressive symptoms, and daytime sleepiness was annually evaluated in PD patients. For each domain a linear mixed-effect model was used to examine changes during follow-up and relations with age and death.
  
  
  RESULTS
  Of 378 included patients, 43 died during follow-up. Higher age was associated with increased severity of all nondopaminergic features except depression, and with a higher rate of progression of axial symptoms and cognitive impairment. Patients who died during follow-up had a higher severity of all nondopaminergic features except autonomic dysfunction, and a higher rate of progression of axial symptoms, cognitive impairment, and psychotic symptoms, compared to patients who survived.
  
  
  CONCLUSIONS
  This study shows that the severity of most nondopaminergic features and the progression rate of axial and psychotic symptoms and cognitive impairment increase before PD patients die, independent of the influence of age. An interaction between age and approaching death did not have a significant effect on the course of the symptoms. Improving our understanding of the fundamental biology underlying these factors and the interaction with factors intrinsic to the disease, may have profound implications for the treatment of PD.
authors.affiliation: Leiden University Medical Centre, Department of Neurology, Leiden, The Netherlands; Leiden University Medical Centre, Department of Medical Statistics and Bioinformatics, Leiden, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: van Rooden
authors.affiliation: Leiden University Medical Centre, Department of Neurology, Leiden, The Netherlands; Academic Medical Center, Department of Neurosurgery, Amsterdam, The Netherlands. Electronic address: D.Verbaan@amc.uva.nl.
authors.forename: D
authors.initials: D
authors.lastname: Verbaan
authors.affiliation: Leiden University Medical Centre, Department of Medical Statistics and Bioinformatics, Leiden, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Stijnen
authors.affiliation: Leiden University Medical Centre, Department of Neurology, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Marinus
authors.affiliation: Leiden University Medical Centre, Department of Neurology, Leiden, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: van Hilten
mesh_terms: D000368:Aged; D000375:Aging; D001342:Autonomic Nervous System Diseases / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000401:mortality*; D012893:Sleep Wake Disorders / Q000209:etiology*; D018709:Statistics, Nonparametric; D013534:Survival
keywords: Age; Death; Nondopaminergic; Parkinson's disease; Progression