Laying the Groundwork for Personalized Medicine in Aphasia Therapy: Genetic an Cognitive Predictors of Restorative Treatment Response

项目摘要 对决定某人是否会这样做的特定于患者的因素的理解不完全 中风后对语言治疗反应良好限制了目标或目标方法的发展 解释了可变性的来源。有很大可能遗传因素在 中风后语言恢复，但致力于研究这一点的研究很少 链接。这项工作的长期目标是通过以下方式最大限度地提高对失语症治疗的反应 将患者特有的因素纳入与治疗计划相关的决策中。整体而言 此应用程序的目标是确定患者特定因素的模式，包括两个 候选基因和认知技能，表明与治疗结果的关系。这个 中心假说是载脂蛋白E和脑源性神经营养因子的基因型之间会有关系，并且 工作记忆对刺激的概括。拟议项目的理由是 确定影响治疗反应性的因素将有助于更好地估计 预后，改进了对个体进行适当治疗方案的分选和直接靶向 以最大化行为收益的认知因素。该项目的两个具体目标是 确定(1)载脂蛋白E和脑源性神经营养因子基因对个体的影响程度 失语症对治疗有反应；(2)工作记忆能力与刺激获得有关 失调症治疗后的刺激泛化。慢性卒中后失语症患者 将接受认知和语言评估，并为遗传学提供唾液样本 在参加线索图片命名疗法之前的分析。预期中的 结果是将BDNF和ApoE的认知分数和基因型别整合到公式中 个体患者对恢复性治疗的反应概率。这一贡献是 预计将具有重大意义，因为它将允许更知情的临床决策和 更好地将资源分配给适当的治疗，从而在该领域取得进展 走向更个性化的医学，而不是一刀切的临床方法。这个 在申请者看来，拟议的研究是创新的，因为它代表了一个实质性的 通过量化遗传和认知变异性的来源来脱离现状 可能会影响对恢复性治疗的反应，申请者提出的可能是 用于临床和研究，以改善患者的预后。

Project Summary Incomplete understanding of patient-specific factors that determine whether someone will respond well to language therapy after stroke limits the development of methods to target or account for sources of variability. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. The long-term goal of this line of work is to maximize response to aphasia therapy by incorporating patient-specific factors into decisions related to treatment planning. The overall objective of this application is to identify patterns of patient-specific factors including two candidate genes and cognitive skills that show a relationship with treatment outcomes. The central hypothesis is that there will be a relationship between ApoE and BDNF genotypes, and working memory on stimulus generalization. The rationale for the proposed project is that the identification of factors that impact treatment responsiveness will allow for better estimation of prognosis, improved triage of individuals into appropriate therapy regimens and direct targeting of cognitive factors to maximize behavioral gains. The two specific aims of the project are to determine the degree to which (1) ApoE and BDNF genotypes influence how individuals with aphasia respond to therapy, and (2) working memory abilities are related to stimulus acquisition and stimulus generalization after anomia therapy. Individuals with chronic post-stroke aphasia will undergo cognitive and language assessment, and provide a saliva sample for genetic analysis prior to participating in a cued picture-naming therapy for anomia. The expected outcomes are to integrate cognitive scores and genotypes for BDNF and ApoE into formulating probabilities of individual patient responsiveness to restorative therapy. This contribution is expected to be significant because it will allow for more informed clinical decision making and better allocation of resources to appropriate treatments, thereby making advances in the field toward more personalized medicine, as opposed to a one-size-fits-all clinical approach. The proposed research is innovative, in the applicants' opinions, because it represents a substantive departure from the status quo by quantifying sources of genetic and cognitive variability that may influence responsiveness to restorative therapy, which the applicants propound can be used both clinically and in research to improve patient outcomes.