Effects of Aerobic Exercise in Parkinson's Disease

• Change in cognition, motor function, quality of life, brain function/structure and biomarkers in response to expected change in fitness [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

• cardiac fitness in response to exercise intervention [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• safety and tolerability of the intervention [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  

Background. Many patients with Parkinson's disease (PD), even in the early stages, suffer from cognitive (especially executive and visuospatial) dysfunction, which can impair critical activities of daily living such as driving. Modest increases in cardiovascular fitness with aerobic exercise improve executive functions and visuospatial abilities in the elderly, possibly by enhanced neuroplasticity due to increase of trophic factors and reduction of inflammatory processes in the brain. Preliminary studies have shown that mild-moderate PD patients tolerate aerobic exercise programs and show cardiovascular fitness and motor function improvements.

Preliminary data. In a cross-sectional pilot study of independently living, fully ambulatory PD patients across a spectrum of physical activity levels, we found that cardiovascular fitness (as indexed by VO2max) was an independent predictor of executive functions, visuospatial abilities, walking speed, level of physical activity, and activities of daily living, even after adjusting for age, education, and motor severity of PD. Subjects with greater fitness and better performance on an executive function task had more favorable activation patterns on fMRI, and tended to have greater brain volumes in regions important for cognition on volumetric MRI.

Hypotheses for this preliminary (Phase I/II) clinical trial:

1. Aerobic exercise intervention in the form of brisk walking will improve cardiovascular fitness (i.e., increase VO2max), which will be associated with increase in trophic factors, decrease in inflammatory markers, favorable changes in activation patterns on functional magnetic resonance imaging (MRI) during executive function tasks, and increased volumes of brain regions relevant for executive functions on morphometric MRI.
2. Aerobic exercise programs using different training formats and settings will have different safety (adverse effects such as cardiopulmonary events, falls), tolerability (compliance, retention, subject impressions), and neurobiological activity.

We will also establish inclusion and exclusion criteria for the subsequent definitive efficacy trial by identifying the demographic, cardiovascular fitness, cognitive and motor function profiles of participants who display an optimal balance of safety, tolerability, and favorable neurobiological effects in this preliminary trial.

Design. We will enroll independently living, fully ambulatory, non-demented PD patients (ages 50-80) who are not on an aerobic exercise program. We will investigate effects of heart rate training format (continuous vs. interval) and exercise setting (group vs. individual at home) . Exercise programs will be conducted 3 times per week for 6 months. Exercise test by cycle ergometry, functional and morphometric MRI, trophic factor and biomarker assays, safety exams and labs (ECG, biochemistry, CBC), tests of parkinsonism and cognition, questionnaires about quality of life, mood, and activities of daily living will be administered at baseline and after the exercise program.

Conclusion. Aerobic exercise has the potential to become an effective and easily accessible treatment for PD that can improve both cognitive and motor dysfunction. Our proposed study aims to understand the mechanism of benefits from aerobic exercise in PD and to optimize this intervention for a definitive clinical trial.