Presentation Type
Poster
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder impacting movement, mood, and cognition. Among those affected, veterans, due to their occupational exposures, are particularly susceptible, contributing to over 110,000 PD cases in the United States. Studies have largely attributed this increased prevalence among veterans to environmental neurotoxins such as Agent Orange, MPTP, and 6-OHDA. However, it remains unclear how neurotoxin exposure load influences biological mechanisms in PD. This study aims to elucidate the influence of neurotoxin load on PD-associated molecular changes, neuroplasticity, neurodegeneration, and cognitive and motor function within a clinical population of the Rio Grande Valley region in Texas.
Methods: Here we conducted a longitudinal, repeated-measures clinical observational study in PD patients with self-reported exposure to neurotoxins and sex-, age-, and occupation-matched healthy controls. Participants underwent comprehensive evaluations at two-time points—enrollment and 2 months—enabling the exploration of neurotoxin-related influences on disease progression. After enrollment, subjects underwent subjective surveys to assess prior neurotoxin exposure, including pesticides, Agent Orange, heavy metals, and other occupational or environmental toxins, and were evaluated for neurotoxins via blood samples. At all time points, we collected MRI and diffusion-weighted imaging (DWI) data to measure neurodegeneration, neurophysiological assessments using transcranial magnetic stimulation (TMS) to measure corticospinal excitability and neuroplasticity, and comprehensive functional evaluations encompassing motor function via MDS-UPDRS and HY scales, cognitive status via SLUMS, handedness via Edinburgh Handedness Inventory, gait analysis via Zeno™ Walkway Gait Analysis System, and arm/hand functionality via Bionik InMotion2 Arm/Hand robot.
Results and Discussion: To date, we have enrolled 7 participants with self-reported exposure to neurotoxins and 2 healthy controls. Enrolled PD subjects' ages ranged from 66 to 87, with 5/7 reporting prior agricultural exposure to Pesticides (Methylbromide / Organochlorides) and 1 PD subject reporting exposure to engine exhaust from aviation fuel. One enrolled patient was withdrawn from the study due to an inability to obtain an MRI. Thus, we evaluated the 6 PD enrolled subjects. Initial motor UPDRS scoring revealed 4/6 patients with mild, 1/6 patients with moderate, and 1/6 patients with severe motor impairment of daily living. In addition, 5/6 patients exhibited mild and 1/6 patients revealed moderate impairment during motor examinations. Pending blood labs, the degree of influence neurotoxin blood has on motor and cognitive function remains to be seen. Data from prior PET studies have shown lower dopamine transporter uptake in all basal ganglia areas, as well as a higher asymmetry index in PD patients exposed to Agent Orange compared to PD patients with no exposure. In addition, PD symptoms have been shown to emerge more on the dominant hand side. Therefore, we expect increased cognitive and motor burden, especially on the dominant side, with increased neurotoxic load.
Conclusion: This research holds considerable promise for advancing our understanding of PD, particularly in the context of neurotoxin-related etiology. By deciphering the molecular pathways influenced by neurotoxin exposure, the study sets the stage for targeted therapeutic interventions and potentially less invasive treatments, thereby improving the outlook for individuals grappling with neurotoxin-related PD.
Academic/Professional Position
Medical Student
Mentor/PI Department
Neuroscience
Recommended Citation
Pokhrel, Abhishekh; Salinas, Daniel; Hack, Nawaz; and Potter-Baker, Kelsey, "Influence of Neurotoxin Load on Parkinson’s Disease Pathophysiology" (2024). Research Symposium. 39.
https://scholarworks.utrgv.edu/somrs/2024/posters/39
Included in
Influence of Neurotoxin Load on Parkinson’s Disease Pathophysiology
Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder impacting movement, mood, and cognition. Among those affected, veterans, due to their occupational exposures, are particularly susceptible, contributing to over 110,000 PD cases in the United States. Studies have largely attributed this increased prevalence among veterans to environmental neurotoxins such as Agent Orange, MPTP, and 6-OHDA. However, it remains unclear how neurotoxin exposure load influences biological mechanisms in PD. This study aims to elucidate the influence of neurotoxin load on PD-associated molecular changes, neuroplasticity, neurodegeneration, and cognitive and motor function within a clinical population of the Rio Grande Valley region in Texas.
Methods: Here we conducted a longitudinal, repeated-measures clinical observational study in PD patients with self-reported exposure to neurotoxins and sex-, age-, and occupation-matched healthy controls. Participants underwent comprehensive evaluations at two-time points—enrollment and 2 months—enabling the exploration of neurotoxin-related influences on disease progression. After enrollment, subjects underwent subjective surveys to assess prior neurotoxin exposure, including pesticides, Agent Orange, heavy metals, and other occupational or environmental toxins, and were evaluated for neurotoxins via blood samples. At all time points, we collected MRI and diffusion-weighted imaging (DWI) data to measure neurodegeneration, neurophysiological assessments using transcranial magnetic stimulation (TMS) to measure corticospinal excitability and neuroplasticity, and comprehensive functional evaluations encompassing motor function via MDS-UPDRS and HY scales, cognitive status via SLUMS, handedness via Edinburgh Handedness Inventory, gait analysis via Zeno™ Walkway Gait Analysis System, and arm/hand functionality via Bionik InMotion2 Arm/Hand robot.
Results and Discussion: To date, we have enrolled 7 participants with self-reported exposure to neurotoxins and 2 healthy controls. Enrolled PD subjects' ages ranged from 66 to 87, with 5/7 reporting prior agricultural exposure to Pesticides (Methylbromide / Organochlorides) and 1 PD subject reporting exposure to engine exhaust from aviation fuel. One enrolled patient was withdrawn from the study due to an inability to obtain an MRI. Thus, we evaluated the 6 PD enrolled subjects. Initial motor UPDRS scoring revealed 4/6 patients with mild, 1/6 patients with moderate, and 1/6 patients with severe motor impairment of daily living. In addition, 5/6 patients exhibited mild and 1/6 patients revealed moderate impairment during motor examinations. Pending blood labs, the degree of influence neurotoxin blood has on motor and cognitive function remains to be seen. Data from prior PET studies have shown lower dopamine transporter uptake in all basal ganglia areas, as well as a higher asymmetry index in PD patients exposed to Agent Orange compared to PD patients with no exposure. In addition, PD symptoms have been shown to emerge more on the dominant hand side. Therefore, we expect increased cognitive and motor burden, especially on the dominant side, with increased neurotoxic load.
Conclusion: This research holds considerable promise for advancing our understanding of PD, particularly in the context of neurotoxin-related etiology. By deciphering the molecular pathways influenced by neurotoxin exposure, the study sets the stage for targeted therapeutic interventions and potentially less invasive treatments, thereby improving the outlook for individuals grappling with neurotoxin-related PD.