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: 10205999
• 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/10205999
• 关键词: Anxiety; Attention; Biological Markers; Brain; Brain Stem; Brain region; Caring; Chronic; Clinical; Cognition; Cognitive; Cognitive deficits; Color; Communities; Corpus striatum structure; Data; Data Set; Development; Diagnosis; Enrollment; Ensure; Equipment and supply inventories; Executive Dysfunction; Health; Healthcare Systems; Hospitals; Impaired cognition; Impairment; Incidence; Individual; Injury; Institutes; Knowledge; Linear Regressions; Link; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measures; Mediator of activation protein; 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; 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; Structure; Symptoms; Testing; Time; Traumatic Brain Injury; United States; Veterans; Visit; Work; base; brain volume; clinical practice; clinically relevant; cognitive function; comorbidity; disability; 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) 在美国非常普遍 州和残疾的主要原因，特别是在我们国家的退伍军人中。新出现的证据表明 轻度或中度 TBI 是后来发展为 PD 的关键危险因素。然而，人们对其影响知之甚少 轻度或中度 TBI 对 PD 症状的影响。具体来说，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 PD 的神经病理学。我们小组的初步工作表明，有远程轻中度病史 TBI 与更大的认知缺陷 (d' = 0.77) 和衰退 (d' = 1.54)、神经精神症状升高相关 症状 (d’ = .55)、运动功能下降 (d’ = .71)、生活质量差 (d’ = .62)，以及 PD 中的脑容量 (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）检查症状 全面、标准化的电池，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 可能导致这种共病的神经病理学基础； 5）确定关系 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。这样的 这些知识将增进我们对轻度至中度 TBI 对 PD 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）的影响 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（即大脑 PD 中的形态测量学）。我们假设认知（特别是执行功能）、神经精神 PD 的症状（例如抑郁、焦虑）、运动功能和生活质量会明显恶化 有轻度或中度 TBI 病史 (PD+TBI) 的患者与无 TBI 病史的 PD 患者相比 （PD-TBI）。我们还假设 PD+TBI 组的运动能力和非功能能力将出现更大程度的下降。 随着时间的推移（即两年），运动症状以及生活质量下降。此外，我们预测 脑容量，特别是与 PD 和/或 TBI 相关的特征性脑区域（即额纹状体） 与 PD-TBI 组相比，PD+TBI 组中的区域）将显着减少。我们将检查 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 且有轻度或中度 TBI 病史的非痴呆个体 (PD+TBI；n = 45) 或 无 TBI 病史（PD-TBI；n = 45）将被纳入拟议的研究。超额招聘15% 旨在解释受试者流失或无法使用的数据，并确保样本的动力充足 尺寸。所有参与者都将接受一系列神经心理学测试来测量认知能力（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 个月随访时进行。在基线处， 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模型进行分析。 这项研究的结果将加深我们对轻度或中度 TBI 病史影响的理解 帕金森病相关症状、生活质量和大脑形态测量。此外，结果将提供必要的 关于 TBI 和 PD 相互作用对神经心理症状和其他症状进展的数据 相关的临床结果。最终，这项研究将为指导临床医生提供重要信息 高危患者的识别、管理和治疗，这反过来又可能对临床产生重大影响 在 VA 医疗保健系统以及更大的科学界内部和外部进行实践。