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: 10248571
• 负责人: STEPHANIE Ann COSENTINO
• 金额: $ 102.63万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10248571
• 关键词: Address; Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Amyloid beta-Protein; Astrocytes; Autopsy; Blood Vessels; Cerebellar Diseases; Cerebellum; Cessation of life; Characteristics; Clinical; Cognition; Cognitive; Cognitive deficits; Complex; Consensus; Counseling; Cytoplasmic Inclusion; Data; Dementia; Development; Diagnosis; Elements; Enrollment; Essential Tremor; Executive Dysfunction; General Population; Goals; Health; High Prevalence; Hospitalization; Impaired cognition; Individual; Kinetics; Knowledge; Lead; Lewy Bodies; Link; Measures; Memory; Memory impairment; Motor; Movement Disorders; Neurobehavioral Manifestations; Neurologic; Outcome; Parkinson Disease; Pathologic; Pathology; Patients; Phenotype; Prevalence; Process; Progressive Supranuclear Palsy; Prospective cohort; Relative Risks; Research; Risk Factors; Severities; Side; Sum; Tauopathies; Tremor; Visit; base; clinical predictors; cognitive process; cognitive testing; cohort; epidemiology study; falls; follow up assessment; follow-up; high risk; mild cognitive impairment; motor disorder; neocortical; nervous system disorder; neuropathology; outcome prediction; prognostic; prospective; tau Proteins; tau aggregation; tau-1; virtual

Essential tremor (ET) is among the most prevalent neurological diseases. Although it was long considered a purely motor disorder, ET is increasingly being regarded as more complex, with an emerging recognition of cognitive dysfunction. While cognitive deficits can be mild, other patients dement. Several epidemiological studies reveal a higher prevalence of mild cognitive impairment (MCI) and 1.5 to 2-fold increased risk of Alzheimer's disease (AD) in ET. Yet the study of cognition/dementia in ET is nascent. Our data are limited and patchy - the most basic “whats” (i.e., clinical features, clinical course) and “whys” (i.e., postmortem basis) are uncharted. In sum, there is a cognitive side to ET, and we know little about it. For the past 4 years, we have established and begun to follow an ET cohort to address several of these unknowns (Clinical-Pathological Study of Cognitive Impairment in ET, COGNET). COGNET is the largest (230 enrolled; 195 living), most comprehensive, and only active prospective cohort of ET patients. Key elements are detailed, motor-free, longitudinal cognitive testing, consensus cognitive diagnoses (normal cognition [NC], MCI, dementia), and autopsy data. The study called for a baseline and two follow-up assessments. Currently, mean follow-up from baseline is only 1.50 ± 0.21 years (range = 0.31 - 2.29). Thirty-five died. The data have allowed us to begin to characterize the cognitive deficits in ET and study their pathological bases. Yet, there remain large, obvious gaps in knowledge. First, clinically, are the cognitive impairments in ET progressive? Do they progress at a faster rate than in the general population? What are the conversion rates to MCI and dementia? What are the clinical predictors of cognitive decline? Are cognitive deficits characteristic of AD predictive of worse clinical outcomes? It turns out that we know virtually nothing about the predictors, course and outcomes of cognitive impairments in ET, and such information cannot simply be taken from the general population. With a cohort now successfully assembled and longitudinal cognitive phenotyping ongoing, COGNET is poised to tackle important prognostic issues regarding the predictors and dynamics of cognitive deficits in ET (Aim 1). Second, pathologically, what is the basis for cognitive deficits in ET? Our studies point to heterogeneous deficits with heterogeneous bases, including AD pathologies. We only have 35 postmortems, and our nascent study of the pathological basis for cognitive deficits must grow and come to maturity (Aim 2). We now propose to continue this cohort, adding new measures to characterize the predictors and outcomes of cognitive impairments in ET. We propose enrolling 100 additional ET cases (proposed total n = 295). AIM 1. To provide the first long-term prospective, longitudinal characterization of cognition in ET to address unanswered prognostic questions about cognitive impairment in ET (e.g., conversion rates to MCI and dementia). AIM 2. To finalize our clinicopatho- logical study of ET by comparing the neuropathological features of 100 ET to 300 matched non-ET cases, and identifying the cognitive predictors of specific neuropathologies, particularly AD and other tauopathies.

原发性震颤(ET)是最常见的神经系统疾病之一。尽管长期以来它被认为是 单纯的运动障碍，ET越来越被认为是更复杂的，随着对 认知功能障碍。虽然认知障碍可能是轻微的，但其他患者会精神错乱。几种流行病学 研究表明，轻度认知功能障碍(MCI)的患病率更高，患病风险增加1.5至2倍 ET中的阿尔茨海默病(AD)。然而，对ET中认知/痴呆的研究还处于起步阶段。我们的数据是有限的 斑块--最基本的“什么”(即临床特征、临床病程)和“为什么”(即尸检依据)是 未知之地。总而言之，外星人有认知的一面，我们对此知之甚少。在过去的4年里，我们已经 建立并开始遵循ET队列，以解决其中几个未知问题(临床-病理 ET认知障碍研究，Cognet)Cognet是最大的(230名注册人员；195名在册人员)， 全面的，且只有一个积极的ET患者预期队列。关键要素是详细的、无电机的、 纵向认知测试、共识认知诊断(正常认知、MCI、痴呆症)，以及 尸检数据。这项研究需要一个基线和两个后续评估。目前，平均后续行动来自 基线仅为1.50±0.21年(范围为0.31~2.29)。其中35人死亡。这些数据使我们能够开始 描述ET的认知缺陷，并研究其病理基础。然而，仍然存在着巨大的、显而易见的 知识上的差距。首先，在临床上，ET患者的认知障碍是进行性的吗？他们的进步速度是不是 比一般人的速度快吗？MCI和痴呆症的转化率是多少？什么是 认知功能减退的临床预测指标？阿尔茨海默病的认知缺陷是否预示着更糟糕的临床 结果呢？事实证明，我们对认知的预测因素、过程和结果几乎一无所知 这些信息不能简单地从普通人群中获取。与一群人 现在已经成功组装，纵向认知表型正在进行，Cognet准备解决 与ET认知缺陷的预测因素和动力学有关的重要预后问题(目标1)。第二, 病理上，ET认知障碍的基础是什么？我们的研究指出了不同的赤字 不同的碱基，包括AD的病理。我们只有35具身体，而我们对 认知缺陷的病理基础必须成长和成熟(目标2)。我们现在提议继续 这一队列，增加了新的措施来表征ET中认知障碍的预测因素和结果。 我们建议增加100个ET病例(建议总数n=295)。目标1.提供第一个长期的 对ET患者认知的前瞻性、纵向描述，以解决未回答的预后问题 ET中的认知障碍(例如，MCI和痴呆症的转化率)。目标2.最终确定我们的临床病理- 通过比较100例ET和300例匹配的非ET患者的神经病理特征对ET的逻辑研究，以及 确定特定神经病变的认知预测因子，特别是阿尔茨海默病和其他神经官能症。