How habitual exercise can benefit Parkinson's disease

Exercise can improve symptoms of Parkinson's disease (PD), including bradykinesia, balance, cognition and quality of life, but the therapeutic mechanisms of benefit are poorly understood. First, this thesis aimed to fill a gap in the literature through a systematic review on the effects of exercise on cognition in PD. This systematic review identified the benefits of exercise for cognition, but found studies seldom involved an intervention over 12 weeks, and few human studies investigated mechanisms of exercise in PD. Therefore, we next tested our novel research question: what are the effects of long-term regular (i.e., habitual) exercise on PD, and what may be the associated mechanisms of benefit for motor and non-motor symptoms? Our study compared 12 PD subjects allocated to one of two matched cohorts (n = 6 each), differing only in regular exercise levels. The primary outcome was dorsal and ventral striatal dopamine release in response to acute exercise (30 min cycling) measured using PET and displacement of [¹¹C]raclopride (RAC) binding potential (BP). The secondary outcomes were response to reward in the ventral striatum measured with BOLD percent signal change (PSC) using fMRI, as well as clinical measures of motor function, cognition, mood and apathy. We found habitual exercisers did not release more striatal dopamine in response to acute exercise. In contrast, we found that habitual exercisers had increased RAC BP in their less affected anterior putamen post-exercise. During the fMRI card task habitual exercisers had greater BOLD PSC compared to baseline and both cohorts had greater activation during the reward phase compared to the anticipation phase. In terms of clinical outcomes, habitual exercisers had greater aerobic capacity (VO₂ peak, confirming cohort allocation), as well as improved finger tapping, peg insertion, faster walking, less depression, more positive affect, and less apathy. In summary, habitual exercise does not affect dopamine release in response to acute exercise, but may impact striatal RAC binding as well as response to reward in the ventral striatum. There may be dopaminergic contributions to the motor and mood benefits from habitual exercise in PD, but this topic requires further study.Medicine, Faculty ofGraduat