Traumatic Brain Injury in Parkinson’s Disease: A Longitudinal Study

帕金森氏病(PD)和创伤性脑损伤(TBI)在美国是非常普遍的疾病 这是造成残疾的一个主要原因，特别是在我们国家的退伍军人中。新出现的证据表明 轻、中度颅脑损伤是以后发展为帕金森病的重要危险因素。然而，人们对这种影响知之甚少。 轻、中度颅脑损伤对帕金森病患者症状的影响。具体地说，迫切需要更好地理解 轻、中度颅脑损伤与神经心理功能、生活质量及预后的关系 帕金森病的神经病理学。我们小组的初步工作表明，远古时期的轻度-中度 脑外伤与更大的认知缺陷(d‘=0.77)和衰退(d’=1.54)、神经精神疾病的升高有关 症状(d‘=.55)，运动功能下降(d’=.71)，生活质量差(d‘=.62)，以及 PD患者的脑体积(d‘s=.61-1.1)。然而，由于这些发现的初步性质，进一步的研究 需要1)在更大的描述性样本中确认这些结果；2)通过 全面、标准化的电池，包括可能受到PD和/或TBI影响的症状；3) 确定轻中度颅脑损伤对帕金森病患者长期预后的纵向影响；4)评估 可能导致这种并存情况的神经病理基础；以及5)决定了这种关系 关键生物标记物和神经心理症状以及长期临床结果之间的关系。是这样的 知识将促进我们对轻中度创伤对帕金森病的影响的理解，并最终将有助于 对这些脆弱个体的治疗和管理。 这项纵向研究的总体目标是确定慢性(受伤后1年)的影响。 轻度或中度脑外伤对认知、神经精神症状、生活质量和神经病理(即大脑)的影响 形态计量学)。我们假设认知(尤其是执行功能)、神经精神 帕金森病患者的症状(如抑郁、焦虑)、运动功能和生活质量将显著恶化 有轻中度颅脑损伤病史(PD+TBI)的患者与无TBI病史的PD患者的比较 (PD-TBI)。我们还假设PD+TBI组将表现出更大的运动和非运动功能下降。 运动症状，以及随着时间的推移(即两年)生活质量下降。此外，我们预测 脑体积，特别是与帕金森病和/或脑外伤(即额叶-纹状体)有关的致病基因脑区 与PD-TBI组相比，PD+TBI组将显著减少。我们将研究 探索性分析中这些症状、生活质量和相关生物标志物之间的关系。 90名患有帕金森病和轻中度脑外伤病史的非痴呆者(帕金森病+脑外伤；n=45)或 无脑损伤病史(帕金森病-脑损伤；n=45)将纳入拟议研究。超额招聘15%将 对受试者的消耗或不可用的数据进行核算，并确保样本有足够的动力 尺码。所有参与者都将接受一系列神经心理测试以测量认知(例如， 执行功能、注意力、记忆力)、神经精神症状(例如，抑郁、焦虑、冷漠、创伤后应激障碍)， 运动功能和生活质量。测试将在基线和24个月的随访中进行。在基线上， 参与者还将接受结构磁共振成像(MRI)扫描。数据将主要是 使用多元线性回归分析以及线性和多变量随机效应建模进行分析。 这项研究的发现将促进我们对轻度或中度脑外伤病史的影响的理解 帕金森病相关症状、生活质量和脑形态计量学。此外，结果将提供至关重要的 关于脑外伤和帕金森病在神经心理症状和其他方面进展的相互作用的数据 相关的临床结果。最终，这项研究将提供重要的信息来指导临床医生在 高危患者的识别、管理和治疗，进而可能对临床产生重大影响。 在退伍军人管理局医疗保健系统内外以及更大的科学界进行实践。

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.