Objective: To predict changes in discrete gait characteristics in early Parkinson’s disease (PD) compared to healthy ageing, using subcortical brain volumes quantified in early disease.

Background: Gait disturbance is a cardinal feature of PD, yet the mechanisms underlying gait impairment and progression are poorly understood, limiting therapeutic management. Quantitative gait measures have been related to regional brain structures in healthy ageing (1), yet few have assessed associations between gait and structural brain imaging parameters in PD. No studies have yet investigated whether structural imaging can be used to predict gait decline in PD, thereby aiding the identification of patients at greater risk of gait decline.

Method: 100 PD patients and 47 healthy age-matched controls completed quantitative gait and 3T magnetic resonance imaging assessments at baseline, a median of six months from diagnosis, through the ICICLE-PD and ICICLE-GAIT studies. From T1-weighted images, subcortical volumes related to motor and cognitive functions were measured using Freesurfer software. Gait was quantitatively assessed at 18 month intervals for up to six years, using an instrumented walkway during two minutes of continuous walking. 16 spatiotemporal gait characteristics from a validated gait model (2) were derived. Within-group linear mixed effects models assessed changes in gait characteristics and predicted gait changes from subcortical volumes.  Models corrected for baseline age, sex and height; PD models also included levodopa equivalent dose.

Results: Preliminary results indicate significant changes in PD gait over the first six years of disease; namely reduced step velocity, step length, step time and swing time, and increased step length variability (p<0.01). The gait of healthy controls did not change significantly over six years.  In PD, baseline thalamus volume predicted declines in step velocity, step length, step length variability and step time (p<0.01). Baseline volumes of the basal ganglia and left hippocampus predicted declines in step velocity and step length (p<0.01).

Conclusion: This is the first study to demonstrate that regional subcortical volumes predict gait progression in early PD. Regions related to both motor and cognitive functions predicted decline in selective gait characteristics, suggesting that patients at a higher risk of gait decline may be stratified and targeted for the remediation of gait dysfunction.

References: 1. Wilson J, Allcock L, Mc Ardle R, Taylor J-P, Rochester L. The neural correlates of discrete gait characteristics in ageing: A structured review. Neuroscience & Biobehavioral Reviews. 2018. 2. Lord S, Galna B, Verghese J, Coleman S, Burn D, Rochester L. Independent domains of gait in older adults and associated motor and nonmotor attributes: Validation of a factor analysis approach. Journals of Gerontology – Series A Biological Sciences and Medical Sciences. 2013;68(7):820-7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/regional-subcortical-volumes-predict-gait-decline-in-early-parkinsons-disease/