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

为失语症治疗的个性化医疗奠定基础：恢复性治疗反应的遗传和认知预测因素

• 批准号: 10242811
• 负责人: Stacy M Harnish
• 金额: $ 46.42万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242811
• 关键词: Alleles; Anomia; Aphasia; Apolipoproteins; Behavioral; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Chronic; Clinical; Cognition; Cognitive; Cues; Data; Family; Foundations; Genetic; Genetic Polymorphism; Genotype; Goals; Healthcare; Individual; Intervention; Language; Language Disorders; Language Therapy; Link; Mission; Names; National Institute on Deafness and Other Communication Disorders; Neuronal Plasticity; Outcome; Participant; Patient-Focused Outcomes; Patients; Pattern; Persons; Play; Probability; Prognosis; Public Health; Recovery; Regimen; Reporting; Research; Resource Allocation; Role; Sample Size; Services; Shiners; Short-Term Memory; Source; Stimulus; Stimulus Generalization; Testing; Therapeutic; Training; Treatment outcome; Triage; Work; aphasia recovery; base; clinical decision-making; cognitive skill; experience; gene therapy; genetic analysis; improved; individual patient; innovation; method development; patient response; personalized medicine; post stroke; response; restorative treatment; saliva sample; stroke-induced aphasia; treatment planning; treatment response

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.

项目摘要 不完全了解患者的具体因素，决定是否有人会 对中风后语言治疗反应良好限制了方法的发展， 解释变异性的来源。很有可能遗传学在 中风后的语言恢复，但很少有研究致力于调查这一点 链接.这一工作的长期目标是最大限度地提高失语症治疗的反应， 将患者特异性因素纳入与治疗计划相关的决策中。整体 本申请的目的是识别患者特异性因素的模式， 候选基因和认知技能与治疗结果的关系。的 中心假设是ApoE和BDNF基因型之间存在关系， 工作记忆对刺激泛化的影响拟议项目的理由是， 确定影响治疗反应的因素将有助于更好地估计 预后，改善个体的分类，使其进入适当的治疗方案，并直接靶向 认知因素来最大化行为收益。该项目的两个具体目标是 确定（1）ApoE和BDNF基因型影响个体的程度， 失语症对治疗有反应;（2）工作记忆能力与刺激获得有关 以及治疗后的刺激泛化。慢性卒中后失语症患者 将接受认知和语言评估，并提供唾液样本进行遗传学检查。 分析之前，参与线索图片命名治疗的命名障碍。预期 结果是将认知评分和BDNF和ApoE的基因型整合到制定 个体患者对恢复性治疗反应的概率。这种贡献 预期意义重大，因为它将允许更明智的临床决策， 更好地将资源分配给适当的治疗，从而在该领域取得进展 走向更加个性化的医疗，而不是一刀切的临床方法。的 在申请人看来，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，申请人提出， 用于临床和研究，以改善患者的治疗效果。