title: Freezing of Gait and its Associations in the Early and Advanced Clinical Motor Stages of Parkinson's Disease: A Cross-Sectional Study.
abstract: BACKGROUND
  Freezing of gait is a common disabling symptom of Parkinson's disease (PD) with limited treatment options. The pathophysiological mechanisms of freezing behaviour are still contentious.
  
  
  OBJECTIVE
  To investigate the prevalence of freezing of gait and its associations with increasing disease severity to gain a better understanding of the underlying pathophysiology.
  
  
  METHODS
  This exploratory study included 389 idiopathic PD patients, divided into four groups; early and advanced PD with freezing of gait, and early and advanced PD without freezing of gait. Motor, cognitive and affective symptoms, REM sleep behaviour disorder and autonomic function were assessed.
  
  
  RESULTS
  Regardless of disease stage, patients with freezing of gait had more severe motor symptoms and a predominant non-tremor phenotype. In the early stages, freezers had a selective impairment in executive function and had more marked REM sleep behaviour disorder. Autonomic disturbances were not associated with freezing of gait across early or advanced disease stages.
  
  
  CONCLUSIONS
  These findings support the notion that impairments across the frontostriatal pathways are intricately linked to the pathophysiology underlying freezing of gait across all stages of PD. Features of REM sleep behaviour disorder suggest a contribution to freezing from brainstem pathology but this does not extend to more general autonomic dysfunction.
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, NSW, Australia.|School of Social Sciences and Psychology, University of Western Sydney, Sydney, NSW, Australia.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Hall
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, NSW, Australia.|Neuroscience Research Australia and School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.|School of Psychology, Stanford University, California, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Shine
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, NSW, Australia.|Neuroscience Research Australia and School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: O'Callaghan
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, NSW, Australia.|Healthy Brain Ageing Program, Ageing Brain Centre, Brain and Mind Centre, University of Sydney, NSW, Australia.
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Walton
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, NSW, Australia.
authors.forename: Moran
authors.initials: M
authors.lastname: Gilat
authors.affiliation: Healthy Brain Ageing Program, Ageing Brain Centre, Brain and Mind Centre, University of Sydney, NSW, Australia.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Naismith
authors.affiliation: Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, NSW, Australia.
authors.forename: Simon J G
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D020233:Gait Disorders, Neurologic / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000453:epidemiology; D015995:Prevalence; D020187:REM Sleep Behavior Disorder / Q000453:epidemiology / Q000209:etiology*
keywords: Parkinson’s disease; disease stage; executive function; freezing of gait; pathophysiology