Alexander Gosch and Faculty Mentor: Mary David, Molecular and Microbiology

Introduction
Essential tremor (ET) is a neurological disorder characterized by symmetrical tremor of the upper limbs. Parkinson’s disease (PD) is a similar disorder, also characterized by tremor, with a few differences: ET tremor is mostly seen during action, while PD tremor is more prevalent while at rest. PD is characterized by problems with walking and balance, while ET is characterized primarily by tremor without balance problems. PD symptoms generally improve with the use of the drug levodopa while ET responds better to the drugs propranolol and primidone.
Complete PD pathology remains unknown; it is believed to be a complex interplay between environmental and genetic factors that begins many years before symptoms onset. ET pathology is also not completely known. Some aspects of ET and PD have been characterized; however, the exact pathology of either disease is not well understood.
We compared the prevalence of PD development in ET patients to age matched population controls obtained from the Vanderbilt University Medical Record Synthetic Derivative (SD) database. We compared the prevalence of PD development to the development of Alzheimer’s disease, Multiple Sclerosis, and Lymphoma to ensure prevalence was not due to general increase in disease diagnosis.
Methodology
Cases and controls were identified from the SD. Criteria for diagnosis for each disease in a patient was determined by the presence of at least two ICD9 or ICD10 billing codes at any time in their medical records of the disease of interest. Individuals were also excluded if they did not have a DNA sample in the BioVU repository.
Because early onset PD is rare and to increase the accuracy of the prevalence comparison between the diseases, we excluded all individuals from our cases below the age of 50. To validate the accuracy of ICD9/10 billing codes as a proxy for disease diagnosis, 50 records for each disease of the five diseases (Parkinson’s Disease, Essential tremor, Alzheimer’s Disease, Multiple Sclerosis, and Lymphoma) were randomly chosen and manually reviewed.
Results
PD prevalence is significantly higher in our ET population subset than in the total population (p < 0.0001). PD prevalence is also higher than each control disease. The trend maintains in each age segment, with odds ratios (OR) ranging from 27.6-7.0 (see Figure 1). The OR for each control disease ranges from 15.7-0.68. Alzheimer’s disease has the highest OR out of each control disease, however, it doesn’t have the same level of increase as PD.
Discussion
Parkinson’s disease is significantly more common in individuals who have been diagnosed with essential tremor than in the general medical population. This suggests that the disease pathologies of both essential tremor and Parkinson’s disease are correlated. Interestingly, the OR for developing PD decreases as the individual ages. It is possible the aging process naturally predisposes individuals to develop PD and masks the effect of ET on PD diagnosis. It is also possible some of the patients are misdiagnosed with ET at an early stage, artificially inflating the OR of the younger cohorts.
It was interesting to note that the odds of developing each control disease were increased in individuals with ET, although not as strongly as with PD. Alzheimer’s Disease was selected as another neurological disease with late onset, like PD. MS was selected as a neurological disease with earlier onset, and Hodgkin’s lymphoma was selected as an unrelated disease control. Alzheimer’s disease had the highest OR (15.49-4.26).
Conclusion
By comparing odd of developing the disease in multiple diseases, we validate the connection to essential tremor does exist and is unique to Parkinson’s disease. Further research into the connection between these two diseases may provide insight into the pathology of both diseases.