Parkinson's disease (PD) is the second most common neurodegenerative disorder which poses an enormous individual and public health burden. Current treatments help transiently with symptoms, but are not curative. There is thus an urgent need for therapies to delay or even reverse the neurodegeneration of the dopaminergic system, which is the main pathological process underlying PD. Randomized clinical trials have shown that exercise improves the symptoms of PD. There is preclinical and preliminary human evidence that exercise directly affects the dopaminergic system. However, it is largely unknown whether exercise also shows neuroprotective effects in humans with PD.
We aim to fill this knowledge gap by investigating the effects of exercise on the dopaminergic system in vivo in humans with PD using neuroimaging. We will use dynamic quantitative positron emission tomography (PET) to measure striatal dopamine transporters (DAT). As DAT expression is regulated by ligand-availability, higher DAT levels are observed after interventions that increase synaptic dopamine levels. Using DAT-PET we will investigate the exercise-related changes in dopaminergic neuronal functioning. We will also use a novel magnetic resonance imaging (MRI) sequence to measure neuronal loss from the substantia nigra. Using MRI we will investigate the exercise- induced changes in the rate of dopaminergic neuronal loss. We have an established collaboration with a PD-specific exercise program ?Beat PD Today?. We will enroll 13 participants for this study from the large pool of Beat PD applicants about to begin exercise. DAT-PET, MRI, and clinical assessments will be performed before and after six months of the sustained high-intensity program. Using rigorous neuroimaging biomarkers, our goal is to demonstrate that high-intensity exercise has measurable effects on the dopaminergic neurons.

Public Health Relevance

Projection Narrative Parkinson's disease (PD) is the fastest growing neurodegenerative disorder, but there is currently no cure. Exercise has been proven to have significant beneficial effects on clinical symptoms, but it is unknown whether exercise has protective effects on the brains of individuals with PD. We will investigate whether 6 months of high-intensity exercise can halt the neurodegeneration underlying PD using magnetic resonance and positron emission tomography imaging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS118764-01
Application #
10070423
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lungu, Codrin Ion
Project Start
2020-08-15
Project End
2022-05-31
Budget Start
2020-08-15
Budget End
2022-05-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520