The Influence of Aerobic Exercise on Non-Motor Symptoms in the Mild-to-Moderate Stages of Parkinson's Disease

While the global prevalence of Parkinson’s Disease is rising exponentially, the disease remains one of the most poorly understood and without a known cure. Significant attention has now been directed towards better understanding the heterogeneous initial development, mild to moderate stages of Parkinson’s Disease. Prodromal and mild-stage Parkinson’s Disease is the timeframe prior the experience of significant motor impairment, often prior to a clinical diagnosis, where individuals are subject to manifesting and compounding non-motor symptoms. Of which, worsen alongside disease progression and have the greatest impact on quality of life. Better understanding of the earlier stages of the disease and identifying the early physiological change that occur, may provide diagnostic and interventional targets for slowing the molecular, symptomatic and physiological deteriorations subject to those living with by Parkinson’s Disease. The therapeutic potential of exercise training is likely at its greatest during the earlier stages of the disease and is advantageous for reducing the severity of symptoms, improving quality of life, and may also slow the progression of the disease. While participation in regular exercise is advocated for, it remains unknown as to the most effective modality for improving non-motor symptoms. Therefore, the aims of the current thesis are to i) establish the most effective exercise modality for improving (or reducing severity of) non-motor symptoms for individuals living with mild to moderate stage Parkinson’s Disease, ii) examine the physiological, perceptual and functional disparity between individuals living with mild to moderate stage Parkinson’s Disease and age-matched apparently healthy individuals and iii) examine the effects of aerobic exercise on the physical, physiological and neurological non-motor symptoms experienced in individuals living with mild to moderate stage Parkinson’s Disease.

The first study in this thesis compared the effects of exercise and dual-task training interventions on non-motor experiences of daily living (NMeDL; MDS-UPDRS) for people living with mild to moderate-stage Parkinson’s Disease. Following a search of eight electronic databases, five randomised control trials were identified as eligible for inclusion, with no dual-task studies deemed suitable. Indirect comparisons of the network meta-analysis revealed tango dancing had clinically meaningful reductions in the NMeDL scores (MD -4.47; 95% CI -8.50 to -0.44 and MD -4.38; 95% CI -7.86 to -0.90), compared to speed treadmill training and body weight resistance training. Compared to control, low confidence evidence suggested that tango dancing and mixed treadmill training improved NMeDL. Conclusively, while modalities including tango dancing and mixed treadmill training were deemed the most effective exercise modalities, it appeared that adoption of exercise participation in the earlier stages of disease may be most effective and thus should be advocated for immediately following a diagnosis of Parkinson’s Disease.

The second study in this thesis examined the effects of a 12-week treadmill training intervention on objective sleep and autonomic nervous system function via heart rate variability assessments in both those living with mild to moderate stage Parkinson’s Disease and apparently healthy individuals. Thirty-six individuals were semi-randomised (randomised by geographical distance from training venue) to a non-exercise control or exercise training group. Participants underwent laboratory testing before completing 12 weeks of training, involving three individual and supervised sessions per week. A high prevalence (81%) of undiagnosed, sleep disordered breathing was identified among the cohort, and this was distributed among those living with Parkinson’s Disease and apparently healthy individuals. Additional to the highly fragmented sleep, low heart rate variability comprising high relative contributions of sympathetic function were identified in both cohorts. In response to exercise, despite not achieving statistical significance, improvements in parasympathetic function, sleep architecture, staging and fragmentations were noted and thus highlight the potential role and importance of continued exercise participation. . As such, interventions aiming to improve sleep or autonomic function, in both those living with mild to moderate stage Parkinson’s Disease or apparently healthy individuals, should be continued beyond 12 weeks.

The final study in this thesis investigated the effect of a 12-week treadmill training intervention on cognitive function, cortical activity and motor function in both those living with mild to moderate stage Parkinson’s Disease and apparently healthy individuals. Thirty-six individuals were semi-randomised (randomised by geographical distance from training venue) to a non-exercise control or exercise training group. Participants underwent laboratory testing before completing 12 weeks of aerobic training, involving three individual and supervised sessions per week. Additional to motor function deficits, cortical slowing in frontal and central regions was identified in those with Parkinson’s Disease prior to the intervention, despite no mild cognitive impairment being identified. Exercise appeared to cease further cortical slowing in those with Parkinson’s Disease, similar to the cortical activity of apparently healthy individuals following intervention. A significant effect of time was identified for six-minute walk test functional assessments, in both training groups (p < 0.001). Collectively, this study demonstrated the role of exercise in preventing continued cortical slowing in those with Parkinson’s Disease, and that motor function can be improved in those living with mild to moderate stages of Parkinson’s Disease.

Collectively, this thesis contributes to the limited body of research investigating the physiology underlying concomitant non-motor symptoms experienced in those living with mild to moderate stage Parkinson’s Disease. This thesis demonstrates the important and essential role of aerobic exercise prescription, participation and continued engagement for improving the severity of non-motor symptoms and preventing further decline in those mild to moderate stage Parkinson’s Disease. This research highlights the important and therapeutic role of exercise prescription and participation, in the management of non-motor symptoms and Parkinson’s Disease.