Preventing Levodopa Induced Dyskinesia in Parkinson's Disease With HMG-CoA Reductase Inhibitors

Long term treatment with levodopa, the gold standard treatment of Parkinson's disease (PD), can lead to the development of abnormal involuntary movements called levodopa induced dyskinesia (LID). The severity of LID can range from mild to severely debilitating. A majority of PD patients will develop LID in their treatment life-time. In a recent study of the MPTP monkey model of PD, statin use was found to reduce LID (45%) without a worsening of Parkinsonism symptoms1. Another study showed rats treated with lovastatin prior to and with initiation of levodopa after substantia nigra lesioning showed dramatically less LID evolution compared to animals without lovastatin exposure2. In this study, the investigators will examine the association of statin use and dyskinesia in a convenience sample Parkinson's disease patients in the Veterans Administration Health Care System. This study is a retrospective three cohort design and will compare statin exposure BEFORE beginning LD, versus statin exposure AFTER LD is begun, versus NO statin exposure in PD subjects controlling for disease characteristics (severity), gender, and total LD exposure The primary endpoint is the severity of LID between the groups after years of opportunity to develop LID. Levodopa-Induced dyskinesia is a major cause of reduced quality of life for Veterans with PD and, in some cases, leads to costly surgical interventions. This project examines the impact of statin use on the presence of LID, and could lead to a future intervention trial. The reduction, delayed onset, or elimination of LID could improve the quality of life of many Veterans nationwide.

Inclusion criteria

• Parkinson's Disease
• Age diagnosed with Parkinson's Disease greater than or equal to 50 years
• Treatment with levodopa greater than or equal to 5 years

Exclusion criteria

• Deep Brain stimulation
• Unable to stand for 1 minute intervals, or sensory deficits in the feet
• Significant cognitive impairment as measured by the Montreal Cognitive Assessment score of < 18
• Subjects with unstable medical or psychiatric conditions (including hallucinations).
• History of unstable medical conditions (i.e. active cardiac disease, recent unwellness, surgery etc.)
• Current use of drugs that may affect parkinsonism or dyskinesia:

• dopamine receptor blocking medications
• depakote
• lithium
• amiodarone
• tetrabenazine
• metoclopramide
• dronabinol
• and illicit drugs such as marijuana (THC)
• cocaine
• methamphetamine
• Statins other than simvastatin or lovastatin, atorvastatin ie. fluvastatin (rationale is that while all other statins are thought to not cross the blood brain barrier well, the central nervous system penetrating nature of others is not perfectly clear and could confound results)