Clinical Pathological Study of Cognitive Impairment in Essential Tremor

特发性震颤认知障碍的临床病理学研究

• 批准号: 9276148
• 负责人: STEPHANIE Ann COSENTINO
• 金额: $ 55.68万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276148
• 关键词: Age; Alzheimer' s Disease; Amnestic Disorder; Autopsy; Biochemical; Brain; Cerebellar Diseases; Cessation of life; Characteristics; Clinical; Clinical Research; Cognition; Cognitive; Cognitive deficits; Complex; Counseling; Data; Dementia; Development; Diagnosis; Disease; Elderly; Essential Tremor; Evaluation; Executive Dysfunction; Future; Goals; Gold; Harvest; Human; Impaired cognition; Investigation; Lead; Life; Link; Literature; Maps; Memory; Modeling; Molecular Profiling; Motor; Nature; Neurobehavioral Manifestations; Neurologic; Neuropsychological Tests; Neuropsychology; Participant; Pathologic; Pathology; Patients; Plant Roots; Prevalence; Process; Progressive Supranuclear Palsy; Protein Isoforms; Purkinje Cells; Relative Risks; Reporting; Research; Research Personnel; Research Proposals; Risk; Risk Factors; Sampling; Secondary to; Severities; Shapes; Sum; Swelling; Tauopathies; Testing; Tremor; Update; base; cognitive development; cognitive performance; cognitive process; complement C2a; demented; epidemiology study; executive function; imaging study; mild cognitive impairment; motor disorder; nervous system disorder; novel; outcome forecast; population based; prognostic; prospective; repository; stem; tau Proteins; tissue resource

PROJECT SUMMARY Essential tremor (ET) is one of the most prevalent neurological diseases. Although the most recognizable clinical feature of ET is tremor, there is emerging evidence that non-motor features (esp. cognitive dysfunction) may be present. A growing number of studies are showing that ET patients have poorer cognitive performance than age-matched controls, yet the cognitive profile among ET patients with cognitive problems has yet to be fully characterized. In some ET patients, the cognitive problems are quite severe. Recent epidemiological studies have demonstrated that ET patients are more likely to have mild cognitive impairment (MCI) than age-matched controls, and an increased risk of dementia (relative risk = 1.64 - 1.89). While ET appears to be a risk factor for the development of cognitive impairment, the cause of cognitive impairment in ET is not currently known. There is early evidence that ET may be associated with an increased risk of developing disorders characterized by tau pathology. The overall goal of the proposed research is to determine the clinical and pathological characteristics of cognitive impairment associated with ET. To accomplish this goal, we plan to perform neuropsychological examinations during life and post-morbid neuropathological examinations on participants in the Essential Tremor Centralized Brain Repository (ETCBR), a well-characterized sample of 250 elderly ET cases who have all already agreed to brain donation (R01NS042859, E. Louis). While their tremor has been well-characterized, neuropsychological testing has been limited to a gross global cognitive evaluation. A central hypothesis for the proposed research is that the majority of ET patients with MCI and dementia will have disorders characterized by tau pathology (Alzheimer's disease or progressive supranuclear palsy). Our 5-year research proposal has two specific aims: Aim 1: Characterize the cognitive profile and assign diagnoses of normal cognition, MCI, or dementia in 250 ET patients at baseline and every 18 months. Aim 2: Characterize the neuropathological features of 100 brains of patients with ET harvested in Years 1 - 5, including >70 with cognitive impairment. This aim will include neuropathological and biochemical studies to characterize the molecular signature of the tau protein. The study will test several hypothesized clinical and clinical-pathological relationships (Hypotheses 1A-C, 2A-C). We expect that the proposed research will elucidate the processes of dementia in ET and, in due course, shape the counseling and treatment of ET patients with cognitive symptoms. We anticipate that these will be the gold standard data for the study and characterization of cognitive impairment in ET for years to come, and a tissue resource for future investigators.

项目摘要 特发性震颤（ET）是最常见的神经系统疾病之一。虽然最 ET的可识别的临床特征是震颤，有新的证据表明，非运动特征 (esp.认知功能障碍）可能存在。越来越多的研究表明， 与年龄匹配的对照组相比，患者的认知能力较差， 在患有认知问题的ET患者中，尚未完全表征。在一些ET 患者的认知问题相当严重。最近的流行病学研究表明， 表明ET患者更有可能患有轻度认知障碍（MCI）， 年龄匹配的对照组，痴呆的风险增加（相对风险= 1.64 - 1.89）。当ET 似乎是认知障碍发展的危险因素，认知障碍的原因是 ET损伤目前尚不清楚。有早期证据表明ET可能与 具有发展以tau病理学为特征的疾病的增加的风险。总目标 研究的目的是确定认知障碍的临床和病理特征， 与ET相关的损伤。为了实现这一目标，我们计划进行神经心理学 对参与者进行的生命期间检查和病后神经病理学检查 特发性震颤集中式大脑储存库（ETCBR），一个250例样本的良好表征 已经同意捐献大脑的老年ET病例（R 01 NS 042859，E. Louis）。 虽然他们的震颤已经得到了很好的表征，但神经心理学测试仅限于 总体认知评估这项研究的一个中心假设是， 大多数患有MCI和痴呆的ET患者将患有以tau蛋白为特征的疾病， 病理学（阿尔茨海默病或进行性核上性麻痹）。我们的5年研究 该提案有两个具体目标：目标1：描述认知概况并分配诊断 在基线和每18个月时，250名ET患者的正常认知、MCI或痴呆。目的 2：描述100例ET患者脑的神经病理学特征， 1 - 5岁，包括>70岁的认知障碍。这一目标将包括神经病理学和 生物化学研究来表征tau蛋白的分子特征。这项研究将测试 几个假设的临床和临床病理关系（假设1A-C，2A-C）。 我们希望这项研究能够阐明ET和ET中痴呆的过程， 适时、塑造ET患者认知症状的咨询与治疗。我们 预计这些将是研究和表征的金标准数据， 未来几年ET的认知障碍，以及未来研究人员的组织资源。