title: Progression of gait dysfunction in incident Parkinson's disease: impact of medication and phenotype.
abstract: Gait impairment in Parkinson's disease (PD) persists despite the use of dopaminergic therapy. Motor phenotype associated with greater postural instability and gait difficulty is related to a greater risk of motor decline and may be influenced by non-dopaminergic pathology. This study documents the progression of gait impairment over 18 months in an incident cohort of PD with regard to phenotype and medication. Gait characteristics were measured in 121 PD and 184 controls, and 18 months later in 108 PD participants. Sixteen gait characteristics were examined with respect to five broad domains for PD and motor phenotype. Correlations between change in levodopa (l-dopa) equivalent daily dose and gait were used to identify dopa-responsive and nonresponsive characteristics. Pace and rhythm deteriorated over 18 months in people with PD, with other gait domains remaining stable. People with a postural instability and gait difficulty phenotype had more impaired gait at baseline compared with a tremor-dominant phenotype, which was most evident in temporal characteristics. In contrast, pace and variability deteriorated over the subsequent 18 months in the tremor-dominant phenotype only. Weak but statistically significant correlations were found between increased l-dopa medication and less deterioration in pace and asymmetry. Significant gait impairment is evident in very early disease despite optimal medication. Change over 18 months is subtle and discrete, and is more pronounced in the tremor-dominant phenotype. Some features of gait are refractory to dopaminergic therapy, implicating a non-dopaminergic contribution. This may explain more temporal gait disturbance in the postural instability and gait difficulty phenotype.
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Brook
authors.initials: B
authors.lastname: Galna
authors.forename: Sue
authors.initials: S
authors.lastname: Lord
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.forename: Lynn
authors.initials: L
authors.lastname: Rochester
mesh_terms: D000368:Aged; D003072:Cognition Disorders / Q000209:etiology; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D015259:Dopamine Agents / Q000009:adverse effects*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D015994:Incidence; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology*; D010641:Phenotype; D016138:Walking
chemical_list: D015259:Dopamine Agents; D007980:Levodopa
keywords: Parkinson's disease; gait; longitudinal; medication; phenotype