Loss of cardiac autonomic innervation is a near universal feature in Parkinson’s disease. In this proposal, we will determine if this feature of PD occurs before motor symptoms develop by analyzing the electrocardiograms (EKGs) of patients with pure REM behavioral disorder (RBD). This population was chosen because of the increasing evidence that the majority of RBD patients have pre-motor PD (Braak Stage 2). If successful, these studies could lead to a low-cost, non-invasive test for early pre-motor Parkinson’s disease.
We will evaluate the electrocardiograms from 47 patients diagnosed with pure RBD who underwent all night sleep recordings at the Stanford Sleep Clinic between 2000 and 2008. Age-and gender matched subjects with insomnia will serve as controls. EKG recordings from RBD patients and control subjects will be downloaded and analyzed using specialized software that employs the well established technique of analyzing heart rate variability (HRV) as a measure of autonomic dysfunction. HRV is influenced by both sympathetic and parasympathetic nervous system and is thus a reliable method of studying the autonomic nervous system. Several time and frequency domain parameters will be used to assess the HRV. These will then be compared to a control population.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
To the best of our knowledge, this will be the first attempt to document loss of autonomic innervation of the heart before motor symptoms of PD develop; we will do this by assessing changes in HRV using a standardized EKG in a population that has a high probability of having pre-motor PD, i.e. patients with RBD. If successful, this project could give birth to a simple screening strategy for pre-motor PD that could be incorporated into an annual physical examination at little or no additional cost.
We predict that patients with RBD will have significant alterations in HRV as measured by electrocardiogram tracings compared to a group of age matched controls without RBD. If this is the case, it will indicate that changes in the peripheral nervous system are an early pre-motor feature of PD and may provide a way to screen the general population very early in the disease process, which will be a critical need once disease modifying therapies are identified.
Dr. Langston demonstrated that measures recorded on an electrocardiogram may provide an early marker of PD. Additional studies are needed to evaluate whether those individuals who demonstrate alterations in heart rate variability actually go on to develop PD. The Foundation is working with Dr. Langston to determine the best next steps for this work.