Validating the Electrocardiogram as a Tool to Identify Pre-motor Parkinson's Disease

Promising Outcomes of Original Grant:
Our goal in the funded RRIA was to determine if a 5 minute EKG recordings in patients with a high probably of having pre-motor PD, i.e., individuals with idiopathic REM sleep behavior disorder (RBD), would show a significant decrease in HRV compared to controls. We have successfully tested this hypothesis and our results indicate that HRV is indeed significantly reduced in RBD. Moreover, in one of the RBD cases who subsequently developed PD, there was further decline in HRV, suggesting that EKG can measure changes in HRV over time.

Objectives for Supplemental Investigation: 
The long-term goal of this project remains the same as our original funded grant, i.e. to develop the EKG as a simple, non-invasive and inexpensive tool to identify pre-motor PD. This supplement will help us to 1) re-contact our original cohort of patients to determine if they have subsequently developed PD and/or other pre-motor signs of PD. and (2) replicate our original findings in a second population of patients with RBD (10 controls and 10 patients with RBD). The first aim is a natural progression of our funded grant as we are now in the unique position of being able to re-contact these individuals to assess their subsequent clinical course after their original EKG was recorded.  As one of the RBD case (who developed PD 8 years after RBD diagnosis) demonstrates this represents an excellent opportunity to further explore HRV as a way to measure disease progression. The second aim will not only allow us to replicate our original observations in a second cohort, but also to validate discriminant analysis developed in our original cohort. 

Importance of This Research for the Development of a New PD Therapy:
HRV has the potential to be a simple, non-invasive screening tool that could be used to easily and repetitively screen the general population for pre-motor PD at very little cost since it could be “piggy-backed” on to a routine EKG recording.  This could allow clinical trials aimed at disease modification to be initiated much earlier, at a time when the pathology is restricted to the peripheral nervous system and/or lower brain stem and thereby enhance the potential for success in identifying effective disease modifying agents. Our case study suggests that HRV can indicate disease progression and others have suggested that HRV correlates with PD severity.  If this is, indeed, the case, HRV may provide an excellent outcome measure for trials of disease-modifying drugs, since changes in HRV are not likely to be confounded by Symptoms & Side Effects effects of current anti-parkinsonian therapies.