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

帕金森病中的创伤性脑损伤：一项纵向研究

• 批准号: 10662458
• 负责人: Dawn M. Schiehser
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10662458
• 关键词: Anxiety; Attention; Biological Markers; Brain; Brain Stem; Brain region; Caring; Chronic; Clinical; Cognition; Cognitive; Cognitive deficits; Color; Communities; Data; Data Set; Development; Diagnosis; Enrollment; Ensure; Equipment and supply inventories; Executive Dysfunction; Health; Healthcare Systems; Hospitals; Impaired cognition; Impairment; Incidence; Individual; Injury; Knowledge; Linear Regressions; Link; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measures; Mediator; Medical; Memory; Mental Depression; Military Personnel; Modeling; Motor; Movement Disorder Society Unified Parkinson' s Disease Rating Scale; Nature; Neurodegenerative Disorders; Neuropsychological Tests; Neuropsychology; Outcome; Parkinson Disease; Participant; Patients; Persons; Pilot Projects; Play; Post-Traumatic Stress Disorders; Prevalence; Quality of life; Recording of previous events; Regression Analysis; Research; Risk; Risk Factors; Role; Sample Size; Sampling; Severities; Standardization; Symptoms; TBI Patients; Testing; Time; Traumatic Brain Injury; United States; Veterans; Visit; Vulnerable Populations; Work; brain volume; clinical practice; clinically relevant; cognitive function; comorbidity; disability; disorder risk; executive function; experience; follow-up; frontal lobe; gray matter; improved; interest; mild traumatic brain injury; morphometry; motor symptom; neuroimaging; neuropathology; neuropsychiatric symptom; neuropsychiatry; non-demented; non-motor symptom; primary outcome; recruit

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.

帕金森病（PD）和创伤性脑损伤（TBI）是美国的高度流行的病症。 国家和残疾的一个主要原因，特别是在我们国家的退伍军人。新出现的证据表明 轻度或中度TBI是以后发展为PD的关键危险因素。然而，人们对它的影响知之甚少， 轻度或中度创伤性脑损伤对帕金森病症状的影响。具体而言，迫切需要更好地了解 轻中度TBI与神经心理功能、生活质量和 帕金森病的神经病理学我们小组的初步工作表明， TBI与更大的认知缺陷（d' = 0.77）和下降（d' = 1.54）、神经精神障碍（d '= 0.77）和神经精神障碍（d'= 0.77）相关。 症状（d' = .55），运动功能下降（d' = .71），生活质量差（d' = .62），以及减少 脑体积（d = 0.61 -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）用 全面、标准化的组合，包括可能受PD和/或TBI影响的症状; 3） 确定轻中度TBI对PD长期结局的纵向影响; 4）评估 可能是这种共病的基础的神经病理学底物;和5）确定 关键生物标志物和神经心理症状以及长期临床结果之间的关系。等 知识将促进我们对PD中轻度-中度TBI影响的理解，并最终有助于 这些弱势群体的治疗和管理。 这项纵向研究的总体目标是确定慢性（受伤后> 1年） 轻度或中度TBI对认知、神经精神症状、生活质量和神经病理学的影响（即，大脑 形态测定法）。我们假设，认知（特别是执行功能），神经精神 症状（例如，抑郁、焦虑）、运动功能和生活质量在PD中将显著恶化 有轻度或中度TBI病史的患者（PD+TBI）与无TBI病史的PD患者相比 （PD-TBI）。我们还假设，PD+TBI组将表现出运动和非运动功能的更大下降。 运动症状以及生活质量随时间的降低（即，两年）。此外，我们预测 脑体积，特别是与PD和/或TBI有关的特异性脑区域（即，额纹状体的 与PD-TBI相比，PD+TBI组中的细胞凋亡（区域）将显著降低。我们会研究 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PD和轻度或中度TBI病史的非痴呆个体（PD+TBI; n = 45），或 无TBI病史（PD-TBI; n = 45）的患者将入组本研究。超额招聘15%， 制定该标准是为了考虑受试者流失或不可用的数据，并确保样本具有足够的把握度 尺寸所有参与者将接受一系列神经心理学测试以测量认知（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。将在基线和24个月随访时进行检查。在基线时， 参加者亦会接受核磁共振扫描。数据将主要 使用多元线性回归分析和线性及多变量随机效应建模进行分析。 这项研究的结果将促进我们对轻度或中度TBI病史影响的理解 PD相关症状、生活质量和脑形态测量学。此外，结果将提供必要的 关于TBI和PD对神经心理症状和其他疾病进展的相互作用的数据 相关临床结果。最终，这项研究将提供重要的信息，以指导临床医生在 风险患者的识别、管理和治疗，这反过来又会显著影响临床 实践内外VA医疗保健系统，以及更大的科学界。