Toward Personalized Prognosis and Outcomes in Primary Progressive Aphasia

原发性进行性失语症的个性化预后和结果

• 批准号: 10634041
• 负责人: BRADFORD C DICKERSON
• 金额: $ 251.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-17 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634041
• 关键词: Acceleration; Affective; Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid; Aphasia; Apraxias; Atrophic; Biological Markers; Brain; Brain imaging; Brain region; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Clinical dementia rating scale; Cognitive; Country; Data; Development; Diagnosis; Diagnostic Procedure; Diagnostic Specificity; Diffusion Magnetic Resonance Imaging; Disease; Family; Frequencies; Frontotemporal Lobar Degenerations; Goals; Image; Individual; International; Language; Language Development; Length; Magnetic Resonance Imaging; Measures; Methods; Modeling; Molecular Diagnosis; Monitor; Motor; Motor Cortex; Nerve Degeneration; Neurodegenerative Disorders; Noise; Outcome; Outcome Measure; Pathology; Patient Monitoring; Patients; Positron-Emission Tomography; Prefrontal Cortex; Primary Progressive Aphasia; Prognosis; Progressive Aphasias; Psycholinguistics; Research; Severities; Signal Transduction; Specificity; Speech; Structure; Sum; Symptoms; Syndrome; Tauopathies; Technology; Tracer; Translating; Work; accurate diagnosis; amyloid imaging; clinical care; cognitive function; efficacious treatment; evidence base; fluorodeoxyglucose positron emission tomography; imaging modality; improved; language impairment; magnetic resonance imaging biomarker; molecular imaging; molecular pathology; neural network; neuropathology; next generation; novel imaging technique; predict clinical outcome; prognostic; prognostic method; prognostication; programs; rate of change; regional atrophy; syntax; tau Proteins; therapeutic development; tool; uptake

Summary/Abstract Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome that involves relentless development of aphasia with relative sparing of other cognitive functions, at least early in its course. There are multiple subtypes as well as multiple underlying pathologies. PPA and its subtypes can be difficult to differentiate from other neurodegenerative disorders and from each other, particularly early in their course. There are currently few clinical tools to assist in the early specific diagnosis of PPA and its subtypes. We have recently made substantial preliminary progress toward the development of novel imaging techniques that could be extremely valuable in early specific diagnosis of the molecular basis of specific pathologies underlying PPA. We propose to use tau and amyloid imaging tracers to attempt to discriminate these underlying molecular pathologies, functional connectivity MRI, diffusion tensor imaging MRI, and morphometric structural MRI to measure and longitudinally monitor markers of neurodegeneration in the language network(s) and other brain regions. In addition to more accurate diagnosis, these measures will likely be important for prognostication and monitoring of decline and the effects of putative therapies. The overall goal of this proposal is to translate these methods from new scientific technologies into clinically useful tools that can be used by clinicians around the country and internationally to improve the diagnostic specificity and assessment capabilities for PPA and its subtypes.

摘要/摘要 原发性进行性失语症 (PPA) 是一种破坏性的神经退行性综合征，涉及 至少，失语症持续发展，而其他认知功能相对较少 在其进程的早期。有多种亚型以及多种潜在的病理。苯丙胺 其亚型可能很难与其他神经退行性疾病区分开来 彼此之间，特别是在他们课程的早期。目前很少有临床工具可以辅助 PPA 及其亚型的早期特异性诊断。 我们最近在小说开发方面取得了实质性的初步进展 成像技术对于分子的早期特异性诊断非常有价值 PPA 的具体病理学基础。我们建议使用 tau 蛋白和淀粉样蛋白成像 示踪剂试图区分这些潜在的分子病理、功能连接 MRI、扩散张量成像 MRI 和形态测量结构 MRI 来测量和 纵向监测语言网络和其他大脑中神经退行性变的标记 地区。除了更准确的诊断之外，这些措施可能对于 预测和监测衰退以及假定疗法的效果。 该提案的总体目标是将这些方法从新的科学技术转化为 转化为临床有用的工具，可供全国和国际各地的临床医生使用 提高PPA及其亚型的诊断特异性和评估能力。