title: Early phenotypic differences between Parkinson's disease patients with and without freezing of gait.
abstract: BACKGROUND
  Previous studies have associated freezing of gait in Parkinson's disease with the presence of specific phenotypic features such as mood disturbances, REM sleep behavior disorder and selective cognitive impairments. However, it is not clear whether these features are present in the earlier stages of disease or simply represent a more general pattern of progression. To investigate this issue, the current study evaluated motor, cognitive, affective and autonomic features as well as REM sleep behavior disorder in Parkinson's disease patients in the early stages of the condition.
  
  
  METHODS
  Thirty-eight freezers and fifty-three non-freezers with disease duration of less than five years and a Hoehn and Yahr stage of less than three were included in this study. The groups were matched on a number of key disease features including age, disease duration, motor severity and dopamine dose equivalence. Furthermore, patients were assessed on measures of motor, cognitive, affective and autonomic features, as well as REM sleep behavior disorder.
  
  
  RESULTS
  Compared to non-freezers, patients with freezing of gait had significantly more non-tremor symptoms and a selective impairment on executive functions, such as set-shifting ability and working memory. Freezers and non-freezers did not differ on measures of tremor, autonomic function, REM sleep behavior disorder, mood or more general cognition.
  
  
  CONCLUSIONS
  These results suggest the pathophysiological mechanisms underlying freezing of gait in the early clinical stages of Parkinson's disease are likely to be related to specific changes in the frontostriatal pathways rather than being due to brainstem or more diffuse neuropathology.
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Research Institute, University of Sydney, NSW, Australia; Centre for Human Movement Sciences, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: julie.hall@sydney.edu.au.
authors.forename: J M
authors.initials: JM
authors.lastname: Hall
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Shine
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Walton
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Gilat
authors.affiliation: Centre for Human Movement Sciences, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Y P T
authors.initials: YP
authors.lastname: Kamsma
authors.affiliation: Healthy Brain Ageing Program, Ageing Brain Centre, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Naismith
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: S J G
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000209:etiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000209:etiology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications*; D010641:Phenotype; D020187:REM Sleep Behavior Disorder / Q000209:etiology; D018709:Statistics, Nonparametric
keywords: Autonomic function; Executive function; Freezing of gait; Mood; Parkinson's disease; REM sleep behavior disorder