Environmental Epidemiology of Essential Tremor
Environmental Epidemiology of Essential Tremor
This study's research is devoted to studying the causes of tremor, and especially essential
 tremor (ET), which is the most common type of tremor. Previous studies have revealed a link
 between harmane [HA], a dietary neurotoxin, and ET; these studies now also suggest a link
 between this toxin and Parkinson's disease (PD), a related tremor disorder. Yet these links
 are tentative rather than conclusively established; therefore, in this new patient-based
 proposal, which incorporates investigations spanning two continents (North America and
 Europe), utilizes several complementary study designs (prospective cohort, case control), and
 draws on several types of tissue (blood, brain), the investigator's goal is to nail down the
 links between HA and ET and to further solidify the emerging links between HA and PD.
This research is devoted to studying the causes of tremor, and especially essential tremor
 (ET), which is the most common type of tremor. Since 2000, this lab has been investigating
 whether several environmental neurotoxins are associated with ET. A link between harmane (HA)
 (1-methyl-9H-pyrido[3,4-b]indole) and ET has been emerging from these studies, which show
 that blood and brain HA concentration ([HA]) is elevated in ET cases (esp. familial ET) vs.
 control subjects. HA is a neurotoxin present in the diet (esp. in meat). Administration of HA
 to laboratory animals produces severe action tremor resembling ET. Yet the link between HA
 and ET has not been convincingly established. All epidemiological studies have been
 case-control studies; thus, it is not clear whether high blood [HA] precedes the onset of ET.
 Aim 1 of this proposal will address this issue. The HA story has also become more complex and
 multi-dimensional. Thus, the investigators were recently intrigued to find that blood [HA]
 was higher in Parkinson's disease (PD) cases than controls in New York. HA is structurally
 similar to MPTP, a neurotoxin closely linked with PD. ET and PD are both tremor disorders;
 some patients develop both disorders (ET+PD; i.e., they are comorbid for the two conditions).
 Whether the HA - PD link is reproducible, whether it tracks with the subtype of PD in which
 tremor rather than bradykinesia/rigidity is the predominant feature, and whether biomarker
 findings from blood also occur in the target organ of interest (i.e., the brain) in PD is not
 known. Aim 2 of this proposal will address this myriad of issues. Finally, whether
 individuals who are comorbid for both ET and PD have the highest blood [HA] is not known. Aim
 3 of this proposal will address this issue. To close these gaps in knowledge, in this
 application, the investigators propose a 5-year study with 3 inter-related aims that draw on
 several types of human tissue (blood, brain): AIM 1: To nail down the links between HA and ET
 by studying the association between baseline blood [HA] and the development of incident ET in
 a cohort study. AIM 2: To further solidify the emerging links between HA and PD by extending
 our observations to another country (Spain). AIM 3: To assess blood levels of HA in patients
 who have both ET and PD (ET+PD). This would be the only study heading in this direction -
 exploring the etiological role of environmental factors, and more specifically toxins, in ET.
 It would thus complement the many ongoing studies searching for ET genes. The study could
 lead to the clear identification of the first modifiable risk factor for ET (i.e., dietary
 HA).This would also be the only study assessing the possible etiological role and tissue
 concentrations of this toxin, HA, which is structurally similar to MPTP, in patients with PD.
Inclusion Criteria:

 -  Essential Tremor

 -  Subjects must be 50 years of age or older.

 -  Subjects must have been diagnosed with Essential Tremor

 -  Subjects must live within 3 hours of UTSW

 -  Parkinson's Disease

 -  Subjects must be 50 years of age or older.

 -  Subjects must have been diagnosed with Parkinson's Disease

 -  Subjects must live within 3 hours of UTSW

 -  Healthy Individuals

 -  Healthy individuals living within 3 hours of UTSW

 -  Subjects must be 50 years of age or older

 -  You are healthy and have not being diagnosed with any neurological disease

 -  Essential Tremor and Parkinson's Disease

 -  Subjects must be 50 years of age or older.

 -  Subjects must have been diagnosed with Essential Tremor

 -  Subjects must have been diagnosed with Parkinson's Disease preceded by at least 3
 years of enrollment in study

 -  Subjects must live within 3 hours of UTSW

 Exclusion Criteria:

 -  Healthy Individuals

 -  Subjects with medical history of neurological conditions

 -  Subjects with family history of neurological condition

 -  Subjects with spouse diagnosed with Essential Tremor or Parkinson's Disease

 -  Essential Tremor

 -  Subjects with medical history of another movement disorder such as Parkinson's
 Disease or dystonia

 -  Subjects with head tremor that preceded hand tremor

 -  Parkinson's Disease

 --Subjects with medical history of Essential Tremor

 -  Essential Tremor and Parkinson's Disease

 -  Criteria that does not meet inclusion