Cognitive & Neural Impairment in Frontotemporal Dementia

认知的

• 批准号: 7803657
• 负责人: MURRAY GROSSMAN
• 金额: $ 41.33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7803657
• 关键词: 3 year old; Agreement; Alzheimer' s Disease; Anterior; Aphasia; Atrophic; Behavior; Behavioral; Biological Neural Networks; Brothers; Case Study; Categories; Characteristics; Clinical; Cognition; Cognitive; Comparative Study; Comprehension; Data; Defect; Development; Diagnostic; Disease; Disinhibition; Dysarthria; Family member; Frontotemporal Dementia; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Genotype; Grant; Image; Impairment; Inferior; Inherited; Insula of Reil; Interruption; Joints; Judgment; Knowledge; Language; Left; Longitudinal Studies; Magnetic Resonance Imaging; Medial; Mediating; Modeling; Monitor; Morphology; Names; Non-aphasic; Parents; Patients; Pattern; Personality; Phenotype; Population; Prefrontal Cortex; Prevalence; Process; Protocols documentation; Receptive aphasia; Relative (related person); Reporting; Resolution; Resources; Risk; Sampling; Semantic Dementias; Semantic memory; Semantics; Short-Term Memory; Social Environment; Social Functioning; Source; Speech; Speech Acoustics; Structure; Subgroup; Testing; Work; aphasic; base; cerebral atrophy; clinical care; cognitive function; comparative; corticobasal degeneration; diagnostic accuracy; frontal lobe; improved; insight; memory process; mild neurocognitive impairment; relating to nervous system; social; tau mutation

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.

上一个赠款时期开发了额颞痴呆（FTD）亚组的临床和成像标准，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。在当前的赠款期间，我们建议继续以假设为驱动性失语症的研究，并系统地研究FTD社会障碍的行为和神经基础。具体目标1：我们将检查具有TAU突变患者的临床无症状家庭成员，以定义FTD的前驱形式。我们还将进行纵向行为和成像研究，以表征患有社会障碍的FTD患者，与我们的工作与进行性失语症相似。特定目的2：语义痴呆（SD）的语义缺陷与降解的对象知识有关，但是 丢失的对象知识的模式是不一致的。我们将检验以下假设：SD中对象特征的诊断值受损。认知和fMRI数据将确定这种疾病的基础，并测试这是否与左腹颞疾病有关。 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.特定目的4：我们的社会功能的两部分模型包括社会知识的特征，以及在社会中实施这些知识的执行资源 语境。我们将检验以下假设：FTD中的社会障碍是由于抑制性控制差和有限的工作记忆，该假设控制了与社会知识相关的规则等因素。我们将使用认知和fMRI数据来检验以下假设：社会障碍是由于包括右侧轨道额叶皮层和前额叶前皮质的大规模神经网络的中断。