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.

帕金森氏病（PD）和创伤性脑损伤（TBI）是曼联的高度普遍状况 国家和残疾的主要原因，尤其是在我们国家的退伍军人中。新兴证据表明 轻度或中等的TBI是后来开发PD的关键危险因素。但是，对影响知之甚少 PD症状的轻度或中度TBI。具体来说，至关重要的是更好地了解 轻度中度TBI与神经心理学功能，生活质量以及 PD中的神经病理学。我们小组的初步工作表明，远程温和的历史 TBI与更大的认知缺陷（D'= .77）和下降（D’= 1.54）有关，神经精神病学升高 症状（D'= .55），运动功能降低（D’= .71），生活质量差（D’= .62）以及减少 脑量（d’s = .61-1.1）。但是，由于这些发现的初步性质，进一步研究 需要1）在更大的描述性样本中确认这些结果； 2）检查症状 全面的标准化电池，包括可能受PD和/或TBI影响的符号； 3） 确定轻度中度TBI对PD长期结局的纵向影响； 4）评估 神经病理底物可能是这种合并症的基础； 5）确定关系 关键生物标志物与神经心理症状以及长期临床结果之间。 知识将促进我们对轻度中度TBI对PD的影响的理解，并最终有助于 这些脆弱的人的治疗和管理。 这项纵向研究的总体目的是确定慢性的影响（受伤以来> 1年） 轻度或中度TBI认知，神经精神症状，生活质量和神经病理学（即大脑 pd中的形态计量学）。我们假设认知（部分执行功能），神经精神病学 PD的症状（例如抑郁，动画），运动功能和生活质量将明显更糟 与没有TBI病史的PD患者相比，患有轻度或中度TBI病史的患者（PD+TBI）患者 （PD-TBI）。我们还假设PD+TBI组将显示运动和非运动的下降幅度更大 随着时间的流逝（即两年），运动症状以及生活质量的降低。而且，我们预测 大脑量，特别是在PD和/或TBI中实现的病理学大脑区域（即额叶纹状体 与PD-TBI相比，PD+TBI组的区域将大大减少。我们将检查 这些符号，生活质量和相关生物标志物之间的关系。 九十个非痴呆的人患有PD和中度或中度TBI病史（PD+TBI; n = 45）或 没有TBI病史（PD-TBI; n = 45）将被纳入拟议的研究。招聘过度降低15％ 建立以说明主题属性或无法使用的数据，并确保有足够的样本 尺寸。所有参与者将被管理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），神经精神症状（例如抑郁，动画，冷漠，PTSD）， 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。基线， 参与者还将进行结构磁共振成像（MRI）扫描。数据将是主要的 使用多个线性回归分析以及线性和多变量随机效应建模进行分析。 这项研究的结果将提高我们对轻度或中等TBI历史的影响的理解 关于与PD相关的症状，生活质量和脑形态计量学。此外，结果将提供必不可少的 关于TBI和PD在神经心理学症状和其他方面的相互作用的数据 相关的临床结果。最终，这项研究将提供重要的信息，以指导临床医生 高危患者的识别，管理和治疗，这反过来可能会显着影响临床 在VA医疗保健系统以及更大的科学界内外实践。