Imaging Brain Function/Structure in Presymptomatic FTD

症状前 FTD 的脑功能/结构成像

• 批准号: 7094778
• 负责人: Charles Dennis Smith
• 金额: $ 31.07万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094778
• 关键词: aging; behavioral /social science research tag; bioimaging /biomedical imaging; brain disorder diagnosis; brain imaging /visualization /scanning; brain mapping; clinical research; cognition; dementia; disease /disorder onset; early diagnosis; executive function; family genetics; functional magnetic resonance imaging; gene mutation; genetic carriers; human subject; language; magnetic resonance imaging; mathematical model; neurogenetics; neuropsychological tests; short term memory

DESCRIPTION (provided by applicant): Frontotemporal dementia (FTD) represents only 10-20% of all dementias, but remains important clinically because of its earlier age of onset compared to Alzheimer's disease (AD), and its characteristic attack on core human qualities ,e.g..compassion, insight and verbal communication. Treatment of FTD, as in AD, is more likely to succeed when applied in the early stages of the underlying pathology than in later stages, when symptoms appear and worsen. Detection of brain pathology is needed prior to these symptoms in order to develop and evaluate such treatments. We propose to use functional and structural magnetic resonance imaging (MRI) to detect brain network functional alterations, and subtle changes in cortical density in the frontal and anterior temporal lobes, in persons without dementia symptoms, but who are destined to develop FTD. The high likelihood of developing FTD is well-defined in identified subjects with mutations in the valosin-containing protein (VCP) gene on chromosome 9 associated with FTD, Paget's disease of bone, and inclusion-body myopathy. These persons will be tested to insure the absence of symptoms and typical cognitive impairments in FTD. Mutation carriers will be compared to non-carrier members of the same families. The first specific aim is to perform functional MRI studies to measure frontal and parietal activation during standard working memory and letter fluency tasks typically performed poorly in persons with early symptoms of FTD. We will also perform a control confrontation naming task, shown in preliminary studies to activate regions of the posterior temporal and occipital regions equally in VCP mutation carriers and in non-carriers. These data will be analyzed using advanced analytical and statisitical techniques, discriminant analysis and hierarchical clustering, to identify carriers most likely to develop future dementia. The second specific aim is to compare regional cortical density measured from three-dimensional structural images between VCP mutation carriers and non-carriers. We will combine the functional and structural measures with cognitive test results to refine our predictive model for dementia. These fundamental studies are expected to demonstrate brain network functional alterations and regionally decreased cortical density in rigorously-defined presymptomatic FTD.

描述（由申请人提供）：额颞叶痴呆 (FTD) 仅占所有痴呆症的 10-20%，但由于与阿尔茨海默氏病 (AD) 相比，其发病年龄较早，且其对人类核心品质的特征性攻击，因此在临床上仍然很重要，例如同情心、洞察力和言语沟通。与 AD 一样，FTD 的治疗在潜在病理的早期阶段比在症状出现并恶化的后期阶段更有可能成功。在出现这些症状之前需要检测大脑病理学，以便开发和评估此类治疗方法。我们建议使用功能和结构磁共振成像（MRI）来检测没有痴呆症状但注定会发展为 FTD 的人的大脑网络功能改变以及额叶和前颞叶皮质密度的细微变化。在已确定的 9 号染色体上含有缬洛辛蛋白 (VCP) 基因突变的受试者中，与 FTD、佩吉特骨病和包涵体肌病相关的受试者发生 FTD 的可能性很高。这些人将接受测试，以确保没有 FTD 症状和典型认知障碍。突变携带者将与同一家族的非携带者成员进行比较。第一个具体目标是进行功能性 MRI 研究，以测量标准工作记忆和字母流畅性任务中额叶和顶叶的激活，这些任务通常在具有 FTD 早期症状的人中表现不佳。我们还将执行一项控制对抗命名任务，初步研究表明，VCP 突变携带者和非携带者的后颞叶和枕叶区域均等地激活。这些数据将使用先进的分析和统计技术、判别分析和层次聚类进行分析，以确定最有可能发展为未来痴呆症的携带者。第二个具体目标是比较从 VCP 突变携带者和非携带者之间的三维结构图像测量的区域皮质密度。我们将把功能和结构测量与认知测试结果结合起来，以完善我们的痴呆症预测模型。这些基础研究预计将证明严格定义的症状前 FTD 中大脑网络功能的改变和区域皮质密度的降低。