Toward Personalized Prognosis and Outcomes in Primary Progressive Aphasia

总结/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， 失语症的持续发展，至少其他认知功能相对保留， 在其早期过程中。有多种亚型以及多种潜在的病理。PPA 其亚型可能难以与其他神经退行性疾病区分， 尤其是在早期阶段目前几乎没有临床工具可以帮助 对PPA及其亚型的早期特异性诊断有重要意义。 我们最近在发展小说方面取得了实质性的初步进展。 成像技术，可能是非常有价值的早期特异性诊断的分子 PPA的具体病理基础。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学，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的神经变性标志物 地区除了更准确的诊断外，这些措施可能对 对衰退的解释和监测以及假定疗法的效果。 这项提案的总体目标是将这些方法从新的科学技术中转化出来 转化为临床有用的工具，可供全国各地和国际上的临床医生使用， 提高PPA及其亚型的诊断特异性和评估能力。

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.