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）：额颞痴呆（FTD）仅占所有痴呆症的10-20％，但由于其早期发病年龄与阿尔茨海默氏病（AD）相比，临床上仍然很重要，并且其对核心人类质量的特征性攻击，例如，compasspassion，Insight，Insight和Verbal Communication。与AD中的治疗相比，在症状出现并恶化时，FTD的治疗在基础病理的早期阶段就更有可能成功。在这些症状之前需要检测脑病理学，以开发和评估此类治疗。我们建议使用功能和结构磁共振成像（MRI）来检测脑网络的功能改变，并在没有痴呆症状的人中，额叶和前颞叶中皮层密度的细微变化，但注定会发展为FTD。在与FTD，Paget的骨骼疾病和纳入体肌病相关的染色体上，含瓣膜蛋白的突变（VCP）基因的受试者鉴定出突变的受试者，识别出突变的受试者的识别受试者的明确定义很高。这些人将经过测试，以确保FTD中缺乏症状和典型的认知障碍。将将突变载体与同一家庭的非载体成员进行比较。第一个具体的目的是进行功能性MRI研究，以测量标准工作记忆和字母流利任务期间的额叶和顶叶激活，通常在FTD早期症状的人中表现较差。我们还将执行一个控制对抗命名任务，在初步研究中显示，以在VCP突变载体和非载体中平均激活后时间和枕骨区域的区域。这些数据将使用高级分析和统计技术，判别分析和分层聚类来分析，以识别最有可能发展未来痴呆症的载体。第二个具体目的是比较从VCP突变载体和非载波之间的三维结构图像测得的区域皮质密度。我们将将功能和结构测量与认知测试结果结合起来，以完善我们对痴呆症的预测模型。这些基本研究预计将证明大脑网络的功能改变，并且在严格定义的预性FTD中，区域性降低了皮质密度。