Exercise as Disease-Modifying Strategy for Parkinson's: a Multidimensional Assessment of Acute and Long-Term Interventions

Parkinson's Disease (PD) is a complex and variable neurodegenerative condition. Due to its progressive nature and lack of effective treatments, a range of motor and non-motor symptoms develop and, usually, lead to disability and disengagement with active lifestyles. Exercise interventions have the potential of improving and sustaining physical and cognitive function in PD, as well as stimulating functional and structural neuroplasticity. Published research suggests that multi-modal (MM) exercise, that also includes cognitive tasks, may be more beneficial than single modalities in improving physical and/or cognitive function. However, there have been contrasting results between studies, owing to differences in study design (mode, timing, amount, and intensity of the exercise) and analytical methods used to measure biomarkers, which makes it difficult to generate conclusions and definitive exercise guidelines for people with PD (PwP). As a result of this, the overall objectives of this thesis were to propose acute and long-term interventions that are beneficial for PwP and can be implemented in real-world settings (at home or in the community), investigate associated functional and cognitive outcomes concurrently, and assess potential mechanisms underlying the neuroprotective effects of exercise interventions (MM, aerobic and combined exercise with cognitive tasks) completed in real-world or clinical environments.

The first study (presented in Chapter 3) evaluates neurotrophins levels (i.e., BDNF and pro-BDNF) as candidate biomarkers for PwP in several sample types (plasma, serum, and saliva) with the aim of improving current inconsistent methodologies that compromise the reliability and validity of these measurements. Optimisation trials of ELISA assays were completed and revealed that the use of an appropriate combination of reagent diluent for each sample type and analyte is key to improve assay performance and measurement accuracy. The samples collected for the studies presented in Chapters 4 and 6 were subsequently analysed following the methodological steps reported in this study. Future work should include these methodological considerations and previous studies not reporting these details must be interpreted with caution.

The second study (Chapter 4) presents the long-term implementation of a weekly community-based MM exercise programme for PwP and shows that exercise attendees improve and maintain function for up to 1, 2 or 3 years. Compared to non-active PwP, PD exercisers improve their mobility, lower extremity strength, cognition and BDNF levels, slowing down PD progression.

Subsequently, focus groups were conducted in the studies presented in chapters 5 and 7 to gain in- depth understanding of participants' views about the MM exercise class and its change towards an online delivery due to the coronavirus 2019 (COVID-19) pandemic. Participant's discussions about the feasibility, practicality, and perceptions of the online class for PD, were gathered to develop guidelines for the online delivery of exercise for PwP.

Finally, using an experimental laboratory setting, chapter 6 further explores the neuroprotective effects of acute bouts of aerobic exercise (alone or combined with cognitively challenging tasks) on cognitive function. This pilot study provides preliminary evidence of the beneficial effects that, both, a second bout of cycling 24h after the first session and cycling combined with cognitive tasks have on cognitive function.

Taken together, both the optimisation and lab-based experimental studies provide directions for future research, such as methodological steps to ensure accurate BDNF and pro-BDNF measurements and exercise interventions that are suggested to elicit cognitive benefits. Furthermore, this thesis provides evidence that a community-based MM exercise programme is able to improve and maintain physical and cognitive functions in PwP. This intervention offered an evidence-based exercise class that had been running for over 4 years and, following COVID-19 pandemic, transitioned from the community towards an online-based setting where it has been successfully running for the last 2 years and is ongoing. Accordingly, this thesis also provides novel insights into the online delivery of MM exercise for PwP and presents guidelines for an appropriate setting-up and delivery of online exercise programmes for health-care professionals and researchers working with PwP.