Parkinson's disease (PD) and Traumatic Brain Injury (TBI) are highly prevalent conditions in the United States and a major cause of disability, particularly among our nation?s Veterans. Emerging evidence suggests that mild or moderate TBI is a critical risk factor for later developing PD. Yet, little is known about the impact of mild or moderate TBI on symptoms in PD. Specifically, there is a vital need to better understand the relationship between mild-moderate TBI and neuropsychological functioning, quality of life, and neuropathology in PD. Preliminary work from our group has indicated that a history of remote mild-moderate TBI is associated with greater cognitive deficits (d? = .77) and decline (d? = 1.54), elevated neuropsychiatric symptoms (d? = .55), decreased motor function (d? = .71), poor quality of life (d? = .62), as well as reduced brain volumes (d?s = .61-1.1) in PD. However, due to the preliminary nature of these findings, further research is needed to 1) confirm these results in a larger, descriptive sample; 2) examine symptoms with a comprehensive, standardized battery, including those symptoms that may be impacted by PD and/or TBI; 3) determine the longitudinal impact of mild-moderate TBI on long-term outcomes in PD; 4) assess the neuropathological substrates that may underlie this comorbid condition; and 5) determine the relationship between critical biomarkers and neuropsychological symptoms as well as long-term clinical outcomes. Such knowledge will advance our understanding of mild-moderate TBI impact in PD and will ultimately aid in the treatment and management of these vulnerable individuals. The overall aim of this longitudinal study is to determine the impact of chronic (> 1 year since injury) mild or moderate TBI on cognition, neuropsychiatric symptoms, quality of life, and neuropathology (i.e., brain morphometry) in PD. We hypothesize that cognition (particularly executive function), neuropsychiatric symptoms (e.g., depression, anxiety), motor function and quality of life will be significantly worse in PD patients with a history of mild or moderate TBI (PD+TBI) compared to PD patients without a history of TBI (PD-TBI). We also hypothesize that the PD+TBI group will demonstrate a greater decline in motor and non- motor symptoms, as well as decrements in quality of life, over time (i.e., two years). Moreover, we predict that brain volumes, specifically pathognomonic brain regions implicated in PD and/or TBI (i.e., fronto-striatal regions) will be significantly reduced in the PD+TBI group compared to PD-TBI. We will examine the relationship among these symptoms, quality of life, and relevant biomarkers in exploratory analyses. Ninety non-demented individuals with PD and a history of mild or moderate TBI (PD+TBI; n = 45) or without a history of TBI (PD-TBI; n = 45) will be enrolled in the proposed study. Over-recruitment by 15% will be instituted to account for subject attrition or unusable data, and to ensure an adequately-powered sample size. All participants will be administered a battery of neuropsychological tests to measure cognition (e.g., executive function, attention, memory), neuropsychiatric symptoms (e.g., depression, anxiety, apathy, PTSD), motor function, and quality of life. Tests will be administered at baseline and 24-month follow-up. At baseline, participants will also undergo a structural magnetic resonance imaging (MRI) scan. Data will be primarily analyzed using multiple linear regression analyses and linear and multivariable random effects modeling. Findings from this study will advance our understanding of the impact of mild or moderate TBI history on PD-related symptoms, quality of life, and brain morphometry. Furthermore, results will provide essential data regarding the interaction of TBI and PD on the progression of neuropsychological symptoms and other relevant clinical outcomes. Ultimately, this study will provide important information to guide clinicians in the identification, management, and treatment of at-risk patients, which in turn, could significantly impact clinical practice within and outside the VA Healthcare System, as well as the greater scientific community.

Public Health Relevance

The prevalence of Parkinson?s disease (PD) and Traumatic Brain Injury (TBI) has increased significantly in military populations, with both of these conditions imposing a heavy health burden on Veterans and the VA Healthcare System. Cognitive impairment, neuropsychiatric symptoms, and poor quality of life (QoL) are common in Veterans who have either PD or a history of mild-moderate TBI, yet the impact of comorbid PD+TBI on these symptoms remains unclear. Preliminary evidence suggests that individuals with PD+TBI have poorer outcomes and reduced brain volume compared to PD patients without TBI. However, a comprehensive and systematic study of mild-moderate TBI impact on neuropsychological outcomes, QoL, and brain morphometry in Veterans with PD is needed. Such knowledge will greatly advance our understanding of the interaction between PD and TBI neuropathologies. Findings from this study have the potential to improve the identification, treatment, and management of at-risk Veterans with PD and/or TBI.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Special Emphasis Panel (ZRD1)
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VA San Diego Healthcare System
San Diego
United States
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