Frontotemporal degeneration: a basis for clinical trials

额颞叶变性：临床试验的基础

• 批准号: 7112235
• 负责人: DAVID S KNOPMAN
• 金额: $ 39.36万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7112235
• 关键词: Alzheimer' s disease; apolipoprotein E; clinical research; cognition; cognition disorders; dementia; frontal lobe /cortex; functional ability; human subject; longitudinal human study; magnetic resonance imaging; neural degeneration; neuroimaging; pathologic process; patient oriented research; tau proteins; temporal lobe /cortex

DESCRIPTION (provided by applicant): In order to test drugs in patients with tauopathies, knowledge of the natural history of the frontotemporal lobar dementias (FTLD) must be expressed in terms suitable for designing clinical trials. Without valid estimates of change over 6 or 12 months, instruments appropriate for trials and sample sizes for the trials simply cannot be determined. We are proposing a 4 year, multi-site, longitudinal study of patients with FTLD in which we will recruit subjects using standardized criteria. The specific aims of this project are 1) determine the ratio between change and variance in cognitive, behavioral and functional instruments in order to estimate power to detect treatment effects with each instrument in future clinical trials; 2) perform serial MR imaging to determine the magnitude of change and its variance in global and regional frontal or temporal brain volume in order to estimate power to detect treatment effects on brain volume in future clinical trials; 3) develop a composite FTLD-subtype-specific cognitive instrument for use in clinical trials; and 4) determine whether ApoE genotype and tau haplotype are associated with rate of progression on cognitive, behavioral, functional or imaging in FTLD. We propose to involve 3 Alzheimer Disease Centers (Mayo Rochester/Jacksonville, UCLA and Arizona) plus the University of California- San Francisco to recruit 120 patients with FTLD. We shall recruit patients with the behavioral-dysexecutive syndrome of fronto-temporal dementia, patients with semantic dementia, and patients with progressive nonfluent aphasia. Operational criteria for these 3 syndromes have been developed that will meet rigorous standards suitable for clinical trial recruitment. Subjects will be examined with cognitive, behavioral, functional assessments as well as MR imaging at baseline and 12 months. Key outcomes will include estimates of change and its variability over 1 year on MR imaging, change on cognitive tasks including the composite task, and change on functional and behavioral measures. While the study will also develop a wealth of new knowledge about the relationships between cognition, behavior and brain structure in FTLD, the essential product of this study will be the principles underlying a rationale design for trials of drugs for FTLD.

描述（由申请人提供）：为了在tau蛋白病患者中测试药物，必须以适合设计临床试验的术语表达对额颞叶痴呆（FTLD）自然史的了解。如果没有对6个月或12个月的变化进行有效的估计，就无法确定适用于试验的工具和试验的样本量。我们提议对FTLD患者进行一项为期4年的多中心纵向研究，我们将使用标准化标准招募受试者。本项目的具体目标是：1）确定认知、行为和功能工具的变化和方差之间的比率，以估计未来临床试验中每种工具检测治疗效果的功效;（二）进行系列MR成像，以确定整体和局部额叶或颞叶脑体积的变化幅度及其方差，以估计检测治疗对大脑影响的功效在未来的临床试验中的体积; 3）开发用于临床试验的复合FTLD亚型特异性认知工具;和4）确定ApoE基因型和tau单倍型是否与FTLD中认知、行为、功能或成像的进展率相关。 我们建议涉及3个阿尔茨海默病中心（马约罗切斯特/杰克逊维尔、加州大学洛杉矶分校和亚利桑那州）以及加州-旧金山弗朗西斯科，以招募120例FTLD患者。我们将招募额颞叶痴呆的行为执行障碍综合征患者、语义性痴呆患者和进行性非流利性失语患者。已经制定了这3种综合征的操作标准，这些标准将符合适用于临床试验招募的严格标准。将在基线和12个月时对受试者进行认知、行为、功能评估以及MR成像检查。关键结局将包括1年内MR成像变化及其变异性的估计值、认知任务（包括复合任务）的变化以及功能和行为指标的变化。虽然这项研究还将开发大量关于FTLD中认知，行为和大脑结构之间关系的新知识，但这项研究的基本成果将是FTLD药物试验的基本设计原则。

项目成果

Effects of age and dementia on temporal cycles in spontaneous speech fluency.

• DOI: 10.1016/j.jneuroling.2011.06.002
• 发表时间: 2011-10
• 期刊: JOURNAL OF NEUROLINGUISTICS
• 影响因子: 2
• 作者: Pakhomov, Serguei V. S.;Kaiser, Eden A.;Boley, Daniel L.;Marino, Susan E.;Knopman, David S.;Birnbaum, Angela K.
• 通讯作者: Birnbaum, Angela K.

A computerized technique to assess language use patterns in patients with frontotemporal dementia.

一种计算机化技术，用于评估额颞痴呆患者的语言使用模式。

• DOI: 10.1016/j.jneuroling.2009.12.001
• 发表时间: 2010-03-01
• 期刊: JOURNAL OF NEUROLINGUISTICS
• 影响因子: 2
• 作者: Pakhomov, Serguei V. S.;Smith, Glenn E.;Marino, Susan;Birnbaum, Angela;Graff-Radford, Neill;Caselli, Richard;Boeve, Bradley;Knopman, David S.
• 通讯作者: Knopman, David S.