Cognitive Training and its Potential to Treat Freezing of Gait in Parkinson’s Disease

Abstract

A rapid and expansive growth in the older population is underway. With this larger group of older adults comes an increasing prevalence of neurodegenerative disorders characterised by cognitive decline and physical disability, such as Parkinson’s disease (PD). Interestingly, particular physical symptoms of PD correspond to a specific pattern of cognitive deficits, such as with freezing of gait (FoG). FoG is common and debilitating, and occurs when a patient is struck by a sudden inability to generate effective stepping and forward progression, leaving them feeling ‘glued to the ground’. Although a motor symptom, FoG has clear cognitive correlates, which have been hypothesised to link with the underlying pathophysiology. This has important implications for treatment, as cognitive enhancement could theoretically improve the symptom. Cognitive training (CT) is a method of improving cognition that has grown in public popularity and research interest. Notwithstanding its limitations, it shows promise as a technique for tackling cognitive decline in older adults and in neurodegenerative disease, which may be translated into the wider community. This Thesis is built around four central aims, as follows: 1) To conduct a multifaceted literature review to explore whether CT is effective in PD, and whether it could be applied to patients with FoG; 2) To expand our knowledge on the relationship between FoG and cognition; 3) To explore how FoG impacts on quality of life (QoL); and 4) To 23 determine if CT can reduce FoG severity in patients with PD via a randomized controlled trial (RCT). These aims are addressed via a multitude of differing approaches and manuscript types. Systematic meta-analysis in addition to more theoretically-based reviews are provided to extensively cover the literature as appropriate to the concepts of CT and FoG in PD. Empiric studies are then given to provide original findings on specific aspects of executive functioning using novel cognitive tasks, as well as how QoL is affected in patients with FoG using questionnaire data. Finally, the last chapter reports on an active-controlled RCT of CT for the treatment of FoG in PD. A number of exciting conclusions can be drawn from this Thesis. Firstly, it has summarized what is now a promising body of evidence to suggest CT is beneficial to short-term cognitive outcomes in people with PD. However, significant changes to methodology are needed, and a number of recommendations for future research are made. The Thesis then goes on to demonstrate that there are specific deficits in executive functioning in patients with FoG. Such findings lend themselves to hypotheses around the pathophysiological underpinnings of FoG, in addition to providing suitable targets for CT interventions. FoG is then shown to be a major contributor to QoL, in the context of other key symptoms present in PD including sleep and mood disturbance. Finally, the major goal of this Thesis is achieved by showing that CT may be able to reduce the severity of FoG with improvements seen in the intervention as compared to an active-24 control group. This result requires replication, but nonetheless stands as an exciting prospect for rehabilitation in this population.