Gait Progression Over 6 Years in Parkinson's Disease: Effects of Age, Medication, and Pathology

Abstract

Background: Gait disturbance is an early, cardinal feature of Parkinson's disease (PD) associated with falls and reduced physical activity. Progression of gait impairment in Parkinson's disease is not well characterized and a better understanding is imperative to mitigate impairment. Subtle gait impairments progress in early disease despite optimal dopaminergic medication. Evaluating gait disturbances over longer periods, accounting for typical aging and dopaminergic medication changes, will enable a better understanding of gait changes and inform targeted therapies for early disease. This study aimed to describe gait progression over the first 6 years of PD by delineating changes associated with aging, medication, and pathology. Methods: One-hundred and nine newly diagnosed PD participants and 130 controls completed at least two gait assessments. Gait was assessed at 18-month intervals for up to 6 years using an instrumented walkway to measure sixteen spatiotemporal gait characteristics. Linear mixed-effects models assessed progression. Results: Ten gait characteristics significantly progressed in PD, with changes in four of these characteristics attributable to disease progression. Age-related changes also contributed to gait progression; changes in another two characteristics reflected both aging and disease progression. Gait impairment progressed irrespective of dopaminergic medication change for all characteristics except step width variability. Conclusions: Discrete gait impairments continue to progress in PD over 6 years, reflecting a combination of, and potential interaction between, disease-specific progression and age-related change. Gait changes were mostly unrelated to dopaminergic medication adjustments, highlighting limitations of current dopaminergic therapy and the need to improve interventions targeting gait decline.

Keywords: Parkinson’s disease; aging; gait; longitudinal; neurological disorders; walking.

Figure 1

Flow chart indicating participant recruitment and attrition throughout the ICICLE-GAIT study. Some participants were readmitted into the study having previously withdrawn due to acute pain or illness.

Figure 2

Change in gait over 6 years for control and Parkinson’s disease (PD) participants for gait characteristics that demonstrated a significant change in PD related to disease progression. Panel (A) shows gait characteristics that significantly changed in PD but not controls so demonstrated change related to disease progression only. Panel (B) shows gait characteristics that significantly changed in PD and control groups, but the rate of change was greater in PD, so demonstrated change related to both aging and disease progression. Bold lines show overall change within each group; faint lines show change for individuals.

Figure 3

Radar plot illustrating the relative change in each gait characteristic over 72-months. The central dotted line represents no change. Deviations from zero along the axes radiating from the center of the plot represent the relative change in each gait characteristic over 72-months within each diagnostic group, calculated as the modeled change per year divided by the standard deviation of the modeled change. Gait characteristics are abbreviated as follows: SV, step velocity; SL, step length; Swi, swing time; ST, Step time; Sta, Stance time; Wid, Step width; sd, standard deviation (gait variability); asy, asymmetry. ^†indicates a significant change in gait in the PD cohort over 72 months; ^‡indicates a significant change in gait in controls over 72 months; *indicates a significantly different rate of change in PD gait compared to the rate of gait change in controls. ^†*Denotes criteria 1 satisfied; ^†‡denotes criteria 2 satisfied; ^†‡*denotes criteria 3 satisfied.