Cognitive & Neural Impairment in Frontotemporal Dementia

认知的

• 批准号: 6851875
• 负责人: MURRAY GROSSMAN
• 金额: $ 32.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6851875
• 关键词: Alzheimer' s disease; aging; bioimaging /biomedical imaging; cerebral degeneration; clinical research; cognition disorders; comprehension; dementia; frontal lobe /cortex; functional magnetic resonance imaging; human subject; longitudinal human study; neural information processing; neurogenetics; neuropathology; neuropsychological tests; prefrontal lobe /cortex; temporal lobe /cortex

The previous grant period developed clinical and imaging criteria for frontotemporal dementia (FTD) subgroups, and tested hypotheses about the cognitive and neural basis for semantic and grammatical aspects of language. In the current grant period, we propose to continue hypothesis-driven studies of progressive aphasia and systematically investigate the behavioral and neural basis for the social disorder in FTD. SPECIFIC AIM 1: We will examine clinically asymptomatic family members of patients with a tau mutation to define a prodromal form of FTD. We will also pursue longitudinal behavioral and imaging studies to characterize FTD patients with a social disorder, paralleling our work with progressive aphasia. SPECIFIC AIM 2: Semantic deficits in Semantic Dementia (SD) have been related to degraded object knowledge, but the pattern of lost object knowledge is inconsistent. We will test the hypothesis that the diagnostic value of object features is impaired in SD. Cognitive and fMRI data will determine the basis for this disorder, and test whether this is related to left ventral temporal disease. SPECIFIC AIM 3: Quantitative acoustic speech analyses and grammatical agreements, combined with fMRI, will test the hypothesis that there are 2 forms of Progressive Non-fluent Aphasia (PNFA) - impaired grammar in comprehension and expression related to left ventral inferior frontal (BA 45/47) disease, and a dysarthric articulatory disorder related to left frontal opercular and insula disease. SPECIFIC AIM 4: Our two-component model of social functioning includes features of social knowledge, and executive resources that mediate implementing this knowledge in a social context. We will test the hypothesis that a social disorder in FTD is due to poor inhibitory control and limited working memory that govern factors such as the rules associated with social knowledge. We will use cognitive and fMRI data to test the hypothesis that a social disorder is due to interruption of a large-scale neural network that includes right medial orbital frontal cortex and anterior prefrontal cortex.

上一个资助期制定了额颞叶痴呆（FTD）亚组的临床和影像学标准，并测试了有关语言语义和语法方面的认知和神经基础的假设。在当前的资助期内，我们建议继续对进行性失语症进行假设驱动的研究，并系统地研究 FTD 社会障碍的行为和神经基础。具体目标 1：我们将检查 tau 突变患者的临床无症状家庭成员，以确定 FTD 的前驱形式。我们还将开展纵向行为和影像学研究，以表征患有社交障碍的 FTD 患者，与我们对进行性失语症的工作并行。具体目标 2：语义痴呆 (SD) 中的语义缺陷与物体知识退化有关，但是 丢失物体知识的模式不一致。我们将检验以下假设：目标特征的诊断价值在 SD 中受到损害。认知和功能磁共振成像数据将确定这种疾病的基础，并测试这是否与左腹颞叶疾病有关。具体目标 3：定量声学语音分析和语法一致性，结合功能磁共振成像，将检验以下假设：进行性不流利失语症 (PNFA) 有 2 种形式 - 与左腹下额叶相关的理解和表达语法受损 (BA 45 /47) 疾病，以及与左额叶岛盖和岛叶疾病相关的构音障碍性关节障碍。具体目标 4：我们的社会功能的两部分模型包括社会知识的特征以及在社会中调解这些知识的执行资源。 语境。我们将检验这样的假设：FTD 中的社交障碍是由于抑制控制不良和工作记忆有限造成的，这些因素控制着与社会知识相关的规则等因素。我们将使用认知和功能磁共振成像数据来检验以下假设：社交障碍是由于包括右内侧眶额叶皮层和前额叶皮层在内的大规模神经网络的中断造成的。