Understanding the influence of anxiety on gait in Parkinson's disease

Abstract

Anxiety is a prevalent non-motor symptom of Parkinson’s disease (PD) and has been linked to motor impairments in PD, yet there is a huge gap in the understanding of whether anxiety affects movement, namely gait, in those with PD. Thus, the main objective of the current thesis was to understand if and how anxiety influences gait in PD and whether dopaminergic replacement therapy mediates this relationship. Three studies were conducted to achieve this objective by using a virtual reality setup where participants were asked to walk in virtual environments with and without threat (i.e. across an ELEVATED plank versus across a plank located on the GROUND). Throughout all of the studies all participants (PD and healthy age-matched controls) had greater levels of anxiety in the ELEVATED condition and walked with a slower velocity, smaller steps and greater step-to-step variability compared to the GROUND condition. These results confirmed that the experimental manipulation was effective in every study. The most interesting results in this thesis found that the ELEVATED condition provoked a greater number of freezing of gait (FOG) episodes in PD Freezers (study 1) and significantly more variable gait specifically in Freezers compared to Non-freezers (study 1) and in those with PD who had high trait anxiety compared to those with PD who had low trait anxiety and healthy control participants (study 2). Highly trait anxious PD also appeared to be less able to use visual feedback about their lower limbs when it was provided (study 3) to improve gait especially in the ELEVATED condition. Notably, the frequency of FOG in Freezers (study 1) and step-to-step variability (among other gait parameters) in highly trait anxious PD (study 2 and 3) were improved with dopaminergic replacement therapy. Furthermore, dopaminergic medication also improved step time variability in highly trait anxious PD when visual feedback about their lower limbs was available (study 3). Taken together, this thesis provides strong evidence to suggest that anxiety influences gait in PD, possibly by demanding shared processing resources at the level of the basal ganglia, which may interfere with other processes (such as processing sensory information) necessary to control gait. Dopaminergic replacement therapy might improve information processing within the basal ganglia and thus alleviate some of the interference due to the competition for shared resources. In conclusion, this thesis has (i) provided evidence that suggests anxiety does have an important impact on gait in PD; (ii) provided a mechanistic explanation for how anxiety exacerbates gait impairments in PD; and (iii) elucidated the role of dopamine in mediating anxiety’s influence on gait in PD. Therefore, this thesis has extended the current understanding of anxiety’s influence on movement in PD which has important implications for better management of anxiety and gait impairments in PD.