Cognition in Essential Tremor: A Neuroimaging and Biomarker Study

特发性震颤的认知：神经影像和生物标志物研究

• 批准号: 10604948
• 负责人: Adrianna Marta Ratajska
• 金额: $ 4.19万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-16 至 2025-05-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604948
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Area; Bilateral; Biological Markers; Brain; Cerebellar Diseases; Cerebellum; Clinical; Cognition; Cognitive; Cognitive deficits; Data; Data Analyses; Deep Brain Stimulation; Dementia; Deposition; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Doctor of Philosophy; Elderly; Environment; Essential Tremor; Family; Glial Fibrillary Acidic Protein; Goals; Heterogeneity; Hippocampus; Image; Impaired cognition; Individual; Infrastructure; Kinetics; Language; Light; Link; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medial; Memory; Mentors; Nature; Nerve Degeneration; Neuroanatomy; Neurocognitive; Neurologic Process; Operative Surgical Procedures; Patients; Persons; Phenotype; Plasma; Posture; Prefrontal Cortex; Process; Productivity; Professional Competence; Programming Languages; Research; Resources; Risk; Sampling; Statistical Computing; Subgroup; System; Techniques; Thalamic structure; Training; Tremor; Water; age related; age related neurodegeneration; base; cognitive change; cohort; computerized data processing; dementia risk; disability; epidemiology study; executive function; imaging approach; in vivo; indexing; innovation; interest; motor disorder; multimodality; nervous system disorder; neural; neural correlate; neurofilament; neuroimaging; neuromechanism; neuropathology; non-demented; peer; predictive marker; programs; skills; tau Proteins; tau-1

PROJECT SUMMARY/ABSTRACT Essential tremor (ET) is among the most prevalent neurological disorders in the world. In addition to the hallmark feature of bilateral kinetic tremor, individuals with essential tremor often present with mild cognitive changes that have been primarily characterized as dysexecutive and viewed as being related to abnormalities in cerebello-cortical networks. However, growing evidence suggests that cognitive difficulties can extend beyond the frontal-executive domain, and epidemiological research has shown that individuals with ET are at an increased risk for developing dementia compared to age-matched peers. Prior research conducted by the applicant identified a subgroup of ET patients who had broader cognitive deficits, including poor memory. This gives rise to the question of whether there may be more widespread neural changes occurring outside cerebellar networks in at least a subset of individuals with ET. Indeed, preliminary findings from neuroimaging and neuropathological studies have suggested that there may be a link between ET and Alzheimer’s disease. Further research is warranted to explore this link, including examining biomarkers associated with cognitive decline. The overall goal of the current study is to better understand the neural correlates of cognition in ET. The proposed study aims to 1) identify cognitive phenotypes in ET using a data-driven (cluster analytic) approach and comprehensive neurocognitive assessment, 2) determine whether different cognitive profiles in ET vary in structural brain changes (i.e., free-water, volume), and 3) to explore whether plasma-acquired biomarkers associated with Alzheimer’s disease are elevated in individuals with ET who have memory-related changes relative to those who do not. Innovative features of the proposed study include determining neuroanatomical correlates of cognition in individuals with ET who have different types of cognitive deficits and use of free-water imaging and plasma biomarkers as sensitive and powerful in vivo markers of early neurodegeneration. Findings from this study may increase current understanding about the nature and heterogeneity of cognitive changes in ET, with the potential to provide further information on the link between ET and dementia. The proposed project will also provide the applicant with additional training beyond that included in her Ph.D. program. Specifically, training goals will include 1) hands-on training in magnetic resonance imaging data processing and analysis with emphasis on structural (T1) and free-water imaging, 2) coursework in neural bases and mechanisms underlying cognitive dysfunction in age-related neurological disorders, 3) didactics in plasma biomarkers associated with Alzheimer’s disease and dementia, 4) training in using programming languages for statistical computing and neuroimaging processing, 5) development of professional and career skills. The applicant is supported by a strong research environment with the necessary resources and infrastructure for completion of the proposed project, as well as a productive mentoring team with specific expertise in the proposed areas of study.

项目摘要/摘要 基本树（ET）是世界上最普遍的神经系统疾病之一。除了 双侧动力学树的标志性特征，具有必需树的个体通常具有温和的认知 主要被视为DySexecectect的变化，并被视为与异常有关 在小脑皮层网络中。但是，越来越多的证据表明认知困难可以扩展 除前期域外，并且流行病学研究表明，患有ET的个体 与年龄匹配的同龄人相比，患痴呆症的风险增加。先前的研究由 申请人确定了一个ET患者的亚组，这些患者的认知缺陷不足，包括记忆力不佳。这 引起的问题是，外面是否可能发生更多宽度神经元变化 至少一部分具有ET的个体的小脑网络。确实，来自神经影像学的初步发现 神经病理学研究表明，ET与阿尔茨海默氏病之间可能存在联系。 有必要进一步研究探索此链接，包括检查与认知相关的生物标志物 衰退。当前研究的总体目标是更好地了解ET中认知的神经相关性。 拟议的研究目的是1）使用数据驱动（群集分析）识别ET中的认知表型 方法和全面的神经认知评估，2）确定是否在 等于结构性大脑变化（即自由水，体积）和3） 与记忆相关的ET患者中，与阿尔茨海默氏病有关 相对于那些没有的变化。拟议研究的创新特征包括确定 具有不同类型的认知缺陷和不同类型的ET患者认知的神经解剖学相关性 将自由水成像和等离子体生物标志物用作早期敏感和强大的体内标记 神经变性。这项研究的发现可能会增加对性质和性质的当前理解 ET认知变化的异质性，并有可能提供有关联系的进一步信息 ET和痴呆症。拟议的项目还将为申请人提供其他培训 包括她的博士学位程序。具体而言，培训目标将包括1）磁动手训练 共振成像数据处理和分析，重点是结构（T1）和自由水成像，2） 神经元基础和机制的课程工作与年龄相关的认知功能障碍基础 疾病，3）与阿尔茨海默氏病和痴呆相关的血浆生物标志物中的教学法，4） 使用编程语言进行统计计算和神经影像处理，5） 专业和职业技能。申请人得到了强大的研究环境的支持 完成拟议项目的资源和基础设施以及一支富有成效的心理团队 在拟议的研究领域具有特定的专业知识。