Determinants of neurodegenerative decline in the aphasic variant of Alzheimer's disease

阿尔茨海默病失语症变体神经退行性衰退的决定因素

• 批准号: 9656047
• 负责人: EMILY J ROGALSKI
• 金额: $ 101.62万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9656047
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid; Anatomy; Anomia; Aphasia; Atrophic; Benchmarking; Biological Markers; Biometry; Brain; Brain Diseases; Caring; Cessation of life; Clinical; Clinical Markers; Clinical Trials; Cognitive; Data; Data Set; Databases; Dementia; Development; Disease; Disease Marker; Disease Progression; Enrollment; Frontotemporal Lobar Degenerations; Funding; Future; Goals; Image; Individual; Infrastructure; Investigation; Knowledge; Language; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Memory Loss; Methods; Molecular; Nerve Degeneration; Neurobiology; Neuropsychological Tests; Neuropsychology; Orphan; Outcome; Participant; Pathologic; Patients; Performance; Phenotype; Population; Positron-Emission Tomography; Primary Progressive Aphasia; Procedures; Process; Protocols documentation; Recording of previous events; Research; Research Personnel; Resources; Rest; Risk Factors; Staging; Structure; Syndrome; Therapeutic; Therapeutic Trials; Time; Variant; Visit; clinical biomarkers; clinical center; clinically relevant; connectome; expectation; experience; frontotemporal degeneration; high risk; in vivo; inclusion criteria; interest; language impairment; longitudinal course; morphometry; multimodality; neurobehavior; neuroimaging; neuropathology; novel therapeutics; programs; prospective; recruit; research study; tau Proteins; tau aggregation; treatment strategy; volunteer

PROJECT SUMMARY/ABSTRACT: Primary progressive aphasia (PPA) is a clinical dementia syndrome caused by neurodegenerative brain disease, with language impairment as the primary feature. PPA is associated with two main classes of underlying neuropathology: Alzheimer’s disease (AD) neuropathology and frontotemporal lobar degeneration (FTLD) neuropathology. Research advances, knowledge and interest in dementias due to FTLD have flourished over the past few years allowing for new dedicated resources (e.g., Advancing Research and Treatment for Frontotemporal Degeneration [ARTFL]), which promise exciting new opportunities for advancing our understanding the disease and for developing therapeutics. Unfortunately, individuals with PPA due to AD have been largely orphaned during this process; failing to meet pathologic inclusion criteria for FTLD studies and failing to meet clinical criteria for AD clinical trials, which tend to focus on individuals with the more typical amnestic phenotype. This is unfortunate because individuals with PPA due to AD represent up to 45% of all PPA cases and these individuals are potentially viable candidates for AD-related therapeutics. The proposed study will longitudinally and quantitatively characterize the clinical, cognitive, functional, neuroanatomic and molecular features of individuals with PPA who have biomarker findings consistent with AD (termed PPA-ADbio+ for this project). Aim 1a will quantitatively characterize longitudinal changes in morphometry (using structural MRI), functional connectivity (using resting state MRI), tau accumulation (with [18F]-AV-1451 Tau- PET) and clinical profiles (using detailed neuropsychological testing) of 50 PPA-ADbio+ participants at 3 consecutive annual visits. Aim 1b will characterize the temporal relationship among the variables measured in Aim 1a. This project represents one of the first prospective multidimensional studies of longitudinal course using the relatively new tau biomarker [18F]-AV-1451 in PPA-ADbio+ individuals. In addition to their theoretical interest, the results from this study are relevant for defining objective biomarkers of disease type and progression, which will inform therapeutic treatment strategies for this relatively underserved dementia population.

项目摘要/摘要： 主要进行性失语症（PPA）是由神经退行性脑疾病引起的临床痴呆综合征， 语言障碍是主要特征。 PPA与两个基本神经病理学的主要类别相关： 阿尔茨海默氏病（AD）神经病理学和额颞叶变性（FTLD）神经病理学。研究 在过去的几年中，由于FTLD引起的痴呆症的进步，知识和兴趣浮动，允许新的 专用资源（例如，额颞变性的研究和治疗[ARTFL]），这是 有望促进我们理解疾病和发展治疗的新机会。 不幸的是，在此过程中，由于AD引起的PPA的个体在很大程度上被孤儿院。未能遇到病理学 FTLD研究的纳入标准，无法满足AD临床试验的临床标准，这些标准倾向于关注 患有更典型的羊膜表型的人。这是不幸的，因为由于广告而患有PPA的人 最多代表所有PPA病例的45％，这些人可能是与广告相关的治疗剂的可行候选者。 拟议的研究将纵向和定量地表征临床，认知，功能， 具有生物标志物发现与AD一致的PPA个体的神经解剖学和分子特征 （该项目称为PPA-ADBIO+）。 AIM 1A将定量地表征形态计量学的纵向变化 （使用结构MRI），功能连通性（使用静止状态MRI），Tau积累（使用[18F] -AV-1451 TAU- 50 ppa-adbio+参与者的PET）和临床轮廓（使用详细的神经心理学测试）连续3个 年度访问。 AIM 1B将表征AIM 1A中测得的变量之间的临时关系。这个项目 代表使用相对较新的TAU的第一个纵向课程的前瞻性多维研究之一 PPA-ADBIO+个体中的生物标志物[18F] -AV-1451。除了它们的理论兴趣外，这项研究的结果是 与定义疾病类型和进展的客观生物标志物有关，这将为治疗治疗提供信息 这种相对服务不足的痴呆症人群的策略。