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.

项目总结/摘要： 原发性进行性失语症（PPA）是由神经退行性脑病引起的临床痴呆综合征， 语言障碍为主要特征。PPA与两种主要类型的潜在神经病理学相关： 阿尔茨海默病（AD）神经病理学和额颞叶变性（FTLD）神经病理学。研究 在过去的几年里，由于FTLD引起的痴呆症的进展、知识和兴趣蓬勃发展， 专用资源（例如，先进的研究和治疗额颞叶变性[ARTFL]），其中 为我们进一步了解疾病和开发治疗方法提供了令人兴奋的新机会。 不幸的是，由于AD而患有PPA的个体在此过程中大部分成为孤儿;未能满足病理学诊断， FTLD研究的入选标准和不符合AD临床试验的临床标准，这些临床试验往往侧重于 具有更典型的遗忘表型的个体。这是不幸的，因为个人与PPA由于AD 占所有PPA病例的45%，这些个体是AD相关治疗的潜在可行候选者。 拟议的研究将纵向和定量表征临床，认知，功能， 具有与AD一致的生物标志物发现的PPA个体的神经解剖学和分子特征 （本项目称为PPA-ADbio+）。目的1a将定量表征形态测量学中的纵向变化 （使用结构MRI）、功能连接性（使用静息状态MRI）、tau累积（使用[18F]-AV-1451 Tau-1451）。 PET）和临床特征（使用详细的神经心理学测试） 年度访问。目标1b将说明目标1a中衡量的变量之间的时间关系。这个项目 代表了使用相对较新的tau的纵向过程的第一个前瞻性多维研究之一 PPA-ADbio+个体中的生物标志物[18 F]-AV-1451。除了他们的理论兴趣，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相关，这将为治疗提供信息 为这一相对缺乏服务的痴呆症人群制定战略。