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Assessing Heart Rate Variability (HRV) in the Parkinson's Associated Risk Study (PARS) Cohort

The objective of this study is to determine if HRV, which is reduced in PD, is significantly reduced in subjects with hyposmia (loss of smell) compared to subjects who are normosmic (normal smell function) in the PARS study group; this is based on the hypothesis that hyposmia may represent a robust feature of pre-motor Parkinson’s disease. Furthermore, this study will investigate if HRV is reduced in subjects with abnormal dopamine imaging (who likely have pre-motor PD) compared to those with normal imaging. This study will take us closer to our long term goal of determining if the EKG can be used to screen for pre-motor PD in the general population, either alone or in combination with a loss of the sense of smell.  
Project Description
Approximately 150 digital EKG recordings will be obtained on 100 hyposmic and 50 normosmic PARS participants. The EKG data will be used to analyze HRV, which will be quantified by time, geometric/non-linear and frequency domain measures. These are well established as indicators of cardiac autonomic dysfunction (CAD) which is a near universal feature of PD when motor signs are evident. We will determine if there are statistically significant differences between measures of HRV in normosmic and hyposmic individuals to determine if HRV as measured by a routine EKG can be added to a battery of tests for pre-motor PD. Similarly, we will determine if there is a relationship between HRV and abnormal dopamine imaging; these studies will include the assessment of a previously developed discriminant function analysis of HRV to see if such analysis can distinguish individuals with a loss of smell from those with normal smell, and from those with abnormal dopamine imaging from those with normal dopamine imaging.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
This study will determine HRV as determined by a routine EKG 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.  HRV determinations could be “piggy-backed” on to routine EKG recordings that are typically carried out at an age when individuals are at increasing risk for PD.  Identifying individuals with pre-motor PD could allow clinical trials aimed at disease modification to be initiated much earlier, at a time when their odds for success are likely to be much better. If successful therapies are identified that can slow disease progression, then identification of pre-motor PD could lead to a strategy for preventing typical PD. 

Anticipated Outcome
At the end of this study, we should be able to determine if: 

1)  Cardiac autonomic dysfunction as determined by a loss of HRV as determined by a  routine EKG is correlated with either a loss of sense of smell or abnormal dopamine imaging.
2)  HRV can differentiate individuals with abnormal olfactory function and/or abnormal dopamine imaging from normal control subjects.  
3)  HRV and olfaction together predicts those subjects with dopamine imaging deficit more effectively than either HRV or olfaction alone.



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