Measuring Parkinson's Disease Progression

Early in the course of Parkinson's disease, a small dose of levodopa (L-DOPA) provides benefit for many hours. The body responds as if the levodopa in the plasma filled a reservoir and then slowly leaked out to produce benefit. With disease progression, even though the same amount of levodopa circulates in the blood, the benefit wears off much faster, as if the reservoir had become leakier. This wearing off of benefit can be characterized by a single number, the effect site rate constant Ke. On average, patients with more severe disease and longer disease duration have a larger ("leakier") Ke when the response to drug is measured using clinical features like tapping speed. Unfortunately, clinical measurements are influenced by confounding factors such as patient fatigue and comfort. A direct, objective brain measure of response to levodopa may improve the reliability of this measurement. Fortunately, we can assess the effect of levodopa on the brain directly, using an MRI machine to measure blood flow in different parts of the brain. For instance, the midbrain has a robust blood flow response to a single, clinically sensible dose of levodopa. This study's goal is to validate MRI measurement of Ke in the brain as an objective, quantitative measure of disease severity in PD. We will do this by comparing MRI-based Ke values from people with PD across a wide range of disease duration and severity. In a subgroup of participants, we will do this measurement twice, once before treatment and once after 6 weeks of treatment with carbidopa-levodopa (Sinemet® and other brand names).

Inclusion criteria

• Age 40-79 at screening
• Meet accepted diagnostic criteria for Parkinson disease

Exclusion criteria

Key exclusion criteria:

• Deep brain stimulator (DBS)
• Pregnancy
• Patients taking a dopamine antagonist (like quetiapine) or dopamine partial agonist (like aripiprazole)
• Metal in the head or eye, or other contraindication to MRI
• Claustrophobia
• Serious neurologic disease other than PD
• Head trauma with loss of consciousness for more than 5 minutes
• Severe or unstable systemic illness
• Certain psychiatric illnesses (dementia, psychosis, current major depression)
• Current alcohol use disorder
• Subjects who feel that going without nicotine for 3-4 hours would be uncomfortable
• Currently taking an extended-release formulation of a dopamine agonist (like Mirapex ER or Requip XL)