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.

项目概要/摘要 特发性震颤（ET）是世界上最常见的神经系统疾病之一。 双侧运动性震颤的标志性特征，患有特发性震颤的个体通常表现出轻度认知功能 主要被定性为执行不良并被视为与异常有关的变化 然而，越来越多的证据表明认知困难可能会延长。 超出了额叶执行域，流行病学研究表明，患有 ET 的人 与年龄相匹配的同龄人相比，患痴呆症的风险增加。 申请人确定了 ET 患者的一个亚组，他们具有更广泛的认知缺陷，包括记忆力差。 引发了一个问题：外部是否可能发生更广泛的神经变化 事实上，神经影像学的初步发现至少在一部分 ET 患者中存在小脑网络。 神经病理学研究表明，ET 与阿尔茨海默病之间可能存在联系。 需要进一步的研究来探索这种联系，包括检查与认知相关的生物标志物 当前研究的总体目标是更好地了解 ET 认知的神经相关性。 拟议的研究旨在 1) 使用数据驱动（聚类分析）来识别 ET 的认知表型 方法和综合神经认知评估，2）确定不同的认知特征是否存在 ET 在大脑结构变化（即自由水、体积）方面有所不同，并且 3) 探讨是否血浆获得性 在患有记忆相关疾病的 ET 患者中，与阿尔茨海默病相关的生物标志物升高 所提出的研究的创新特征包括确定那些不这样做的人的相对变化。 具有不同类型认知缺陷的 ET 个体认知的神经解剖学相关性 使用自由水成像和血浆生物标志物作为早期早期敏感和强大的体内标志物 这项研究的结果可能会增加目前对神经退行性变的性质和认识。 ET 认知变化的异质性，有可能提供关于两者之间联系的进一步信息 ET 和痴呆症。拟议的项目还将为申请人提供除此之外的额外培训。 具体来说，培训目标将包括 1) 磁学实践培训。 共振成像数据处理和分析，重点是结构 (T1) 和自由水成像，2) 年龄相关神经系统认知功能障碍的神经基础和机制课程 疾病，3) 与阿尔茨海默病和痴呆症相关的血浆生物标志物的教学，4) 培训 使用编程语言进行统计计算和神经影像处理，5）开发 申请人拥有强大的研究环境和必要的支持。 完成拟议项目的资源和基础设施，以及富有成效的指导团队 在拟议的研究领域具有特定的专业知识。