Progression of gait dysfunction in incident Parkinson's disease: Impact of medication and phenotype

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. © 2014 International Parkinson and Movement Disorder Society

[1]  R. Mehanna Gait speed in Parkinson disease correlates with cholinergic degeneration , 2014, Neurology.

[2]  B. Galna,et al.  The nature of dual-task interference during gait in incident Parkinson’s disease , 2014, Neuroscience.

[3]  J. Jankovic,et al.  Parkinson disease subtypes. , 2014, JAMA neurology.

[4]  Lynn Rochester,et al.  Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6 , 2014, Movement disorders : official journal of the Movement Disorder Society.

[5]  T. Robbins,et al.  Characterizing mild cognitive impairment in incident Parkinson disease , 2014, Neurology.

[6]  B. Galna,et al.  Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences , 2013, Journal of Neurology.

[7]  Lynn Rochester,et al.  Moving forward on gait measurement: Toward a more refined approach , 2013, Movement disorders : official journal of the Movement Disorder Society.

[8]  Lynn Rochester,et al.  Independent domains of gait in older adults and associated motor and nonmotor attributes: validation of a factor analysis approach. , 2013, The journals of gerontology. Series A, Biological sciences and medical sciences.

[9]  J. Jankovic,et al.  How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson's disease rating scale: Comparison with the unified Parkinson's disease rating scale , 2013, Movement disorders : official journal of the Movement Disorder Society.

[10]  Lynn Rochester,et al.  Mild depressive symptoms are associated with gait impairment in early Parkinson's disease , 2013, Movement disorders : official journal of the Movement Disorder Society.

[11]  Lynn Rochester,et al.  Is gait variability reliable in older adults and Parkinson's disease? Towards an optimal testing protocol. , 2013, Gait & posture.

[12]  Joe R. Nocera,et al.  Correction: Quantitative Normative Gait Data in a Large Cohort of Ambulatory Persons with Parkinson’s Disease , 2012, PLoS ONE.

[13]  B. Galna,et al.  Cholinergic dysfunction contributes to gait disturbance in early Parkinson's disease. , 2012, Brain : a journal of neurology.

[14]  Chris J. Hass,et al.  Quantitative Normative Gait Data in a Large Cohort of Ambulatory Persons with Parkinson’s Disease , 2012, PloS one.

[15]  R. Gross Spotlight on the July 3 Issue , 2012, Neurology.

[16]  V. Mok,et al.  Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson's disease patients , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[17]  R. Collins,et al.  Gait variability in Parkinson’s disease: influence of walking speed and dopaminergic treatment , 2011, Neurological research.

[18]  Lynn Rochester,et al.  Gait variability in Parkinson’s disease: an indicator of non-dopaminergic contributors to gait dysfunction? , 2011, Journal of Neurology.

[19]  C. Clarke,et al.  Systematic review of levodopa dose equivalency reporting in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[20]  M H Cole,et al.  Predictors of future falls in Parkinson disease , 2010, Neurology.

[21]  W. Heiser,et al.  The identification of Parkinson's disease subtypes using cluster analysis: A systematic review , 2010, Movement disorders : official journal of the Movement Disorder Society.

[22]  I. McKeith,et al.  Poor attentional function predicts cognitive decline in patients with non-demented Parkinson’s disease independent of motor phenotype , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[23]  M. Ferrarin,et al.  Locomotor Function in the Early Stage of Parkinson's Disease , 2007, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[24]  William W. McDonald,et al.  Depression rating scales in Parkinson's disease: Critique and recommendations , 2007, Movement disorders : official journal of the Movement Disorder Society.

[25]  Jeffrey M. Hausdorff,et al.  Gait asymmetry in patients with Parkinson’s disease and elderly fallers: when does the bilateral coordination of gait require attention? , 2007, Experimental Brain Research.

[26]  J. Jankovic,et al.  Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Process, format, and clinimetric testing plan , 2007, Movement disorders : official journal of the Movement Disorder Society.

[27]  Jeffrey M. Hausdorff,et al.  Marked alterations in the gait timing and rhythmicity of patients with de novo Parkinson's disease , 2006, The European journal of neuroscience.

[28]  D. Aarsland,et al.  Changes in motor subtype and risk for incident dementia in Parkinson's disease , 2006, Movement disorders : official journal of the Movement Disorder Society.

[29]  I. McKeith,et al.  Motor subtype and cognitive decline in Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[30]  S. Studenski,et al.  Too much or too little step width variability is associated with a fall history in older persons who walk at or near normal gait speed , 2005, Journal of NeuroEngineering and Rehabilitation.

[31]  M. Morris,et al.  Three‐dimensional gait biomechanics in Parkinson's disease: Evidence for a centrally mediated amplitude regulation disorder , 2005, Movement disorders : official journal of the Movement Disorder Society.

[32]  W. Poewe,et al.  Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: Status and recommendations The Movement Disorder Society Task Force on rating scales for Parkinson's disease , 2004, Movement disorders : official journal of the Movement Disorder Society.

[33]  M. Vokaer,et al.  Effects of levodopa on upper limb mobility and gait in Parkinson’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[34]  I. McKeith,et al.  SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders , 2003, Movement disorders : official journal of the Movement Disorder Society.

[35]  F. Horak,et al.  Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease , 2002, Journal of neurology, neurosurgery, and psychiatry.

[36]  J. Summers,et al.  Abnormalities in the stride length‐cadence relation in parkinsonian gait , 1998, Movement disorders : official journal of the Movement Disorder Society.

[37]  F. Horak,et al.  Effects of dopamine on postural control in parkinsonian subjects: scaling, set, and tone. , 1996, Journal of neurophysiology.

[38]  J. Summers,et al.  Stride length regulation in Parkinson's disease. Normalization strategies and underlying mechanisms. , 1996, Brain : a journal of neurology.

[39]  E. Smets,et al.  The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. , 1995, Journal of psychosomatic research.

[40]  J. Summers,et al.  The pathogenesis of gait hypokinesia in Parkinson's disease. , 1994, Brain : a journal of neurology.

[41]  Diane Podsiadlo,et al.  The Timed “Up & Go”: A Test of Basic Functional Mobility for Frail Elderly Persons , 1991, Journal of the American Geriatrics Society.

[42]  J. Jankovic,et al.  Variable expression of Parkinson's disease , 1990, Neurology.

[43]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[44]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[45]  E. Protas,et al.  Effects of levodopa on forward and backward gait patterns in persons with Parkinson's disease. , 2011, NeuroRehabilitation.

[46]  L. E. Powell,et al.  The Activities-specific Balance Confidence (ABC) Scale. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.