Optimizing Targeted Interventions for Primary Progressive Aphasia

优化原发性进行性失语症的针对性干预措施

• 批准号: 10712767
• 负责人: Jessica D Richardson
• 金额: $ 36.46万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712767
• 关键词: Adjuvant Therapy; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Aphasia; Applications Grants; Award; Behavior; Brain; Cephalic; Clinical; Communication impairment; Consensus; Data Set; Development; Disease; Disease Management; Electric Stimulation; Electrodes; Electroencephalography; Etiology; Failure; Foundations; Frontotemporal Dementia; Functional disorder; Funding; Future; Goals; Guidelines; Instruction; Intervention; Investigation; Knowledge; Life; Mission; Modeling; National Institute on Deafness and Other Communication Disorders; Nature; Neurobiology; Organism; Outcome; Parents; Persons; Population; Primary Progressive Aphasia; Progressive Aphasias; Prophylactic treatment; Protocols documentation; Public Health; Recovery; Research; Resource Sharing; Stroke; Time; Treatment outcome; United States National Institutes of Health; Variant; brain based; burden of illness; clinical translation; disability; economic impact; improved; innovation; neurological rehabilitation; neurophysiology; neuroregulation; parent grant; personalized approach; prevent; psychosocial; stroke-induced aphasia; therapy development; tool; transcranial direct current stimulation; translational potential; treatment optimization; wasting

PROJECT SUMMARY/ABSTRACT Treatment options for primary progressive aphasia (PPA), a communication disorder associated with fronto- temporal dementia (FTD) or Alzheimer’s Disease (AD) pathology, are extremely limited, and the psychosocial and economic impacts of PPA are devastating. Knowledge of modifiable brain targets has not been harnessed to catalyze meaningful treatment outcomes. Transcranial electrical stimulation (tES) allows systematic investi- gations of the effects of brain target engagement and has strong clinical translational potential. While tES re- search in PPA is encouraging, the over-reliance on tES protocols and recovery models used for stroke-induced aphasia, rather than the development of approaches motivated by PPA neurobiology, has prevented vertical progress in PPA treatment development. The fundamental underlying pathophysiology of progressive aphasia warrants tailored approaches to intervention. There is a critical need for rigorous investigations that facilitate identification of treatments capable of engaging modifiable brain targets for prophylaxis, restitution, and overall improved disease management in PPA and other AD/ADRD. Failure to meet this need will unnecessarily delay treatment advancements for clinical populations with no time to waste. The long-term goal of both the parent grant and this supplement is to optimize neurorehabilitation for aphasia, whether due to stable or progressive etiology, with clinically translatable brain-based treatments. The overall objective of this project is to strengthen the impact of a current project on tES in stroke-induced aphasia (R01DC018282) by identifying and optimizing adjunctive treatments that engage brain targets in people with PPA. This requires a neurotargeting foundation grounded in PPA (rather than stroke) neurobiology and disease trajectory. Innovative pipelines developed in the parent grant will be leveraged and combined with innovations in brain target selection specific to PPA and its three consensus-based variants to develop essential tES tools and guidelines. Two specific aims will be pursued: 1) Develop pipelines and guidelines for targeted modulation of intact cortex for each PPA variant; and 2) Use EEG to identify networks for targeting with tES for each PPA variant. Under the first aim, a shareable pipeline for E-field modeling of multi-electrode transcranial direct current stimulation (tDCS) will be developed, as will a normative dataset of modeled E-field distributions. Under the second aim, spectral EEG differences between controls and people with PPA will be localized, laying the groundwork for future research with tran- scranial alternating current stimulation (tACS). These contributions will be significant because the anticipated development and sharing of resources will advance the validity and inferential precision of tES research for PPA and other AD/ADRD, supporting development of future grant applications specific to neuromodulatory ad- juvant treatments in these clinical populations who are in desperate need of innovations.

项目总结/摘要 原发性进行性失语症（PPA）的治疗选择，这是一种与额- 颞叶痴呆（FTD）或阿尔茨海默病（AD）病理学的研究非常有限， PPA的经济影响是毁灭性的。关于可改变的大脑目标的知识还没有被利用 催化有意义的治疗结果。经颅电刺激（tES）允许系统研究 脑靶点参与的影响，并具有很强的临床转化潜力。当tES重新- PPA中的搜索是令人鼓舞的，过度依赖tES协议和用于中风诱导的恢复模型， 失语症，而不是PPA神经生物学激发的方法的发展，阻止了垂直 PPA治疗进展。进行性失语症的基本病理生理学 需要采取有针对性的干预办法。迫切需要进行严格的调查， 确定能够使可改变的大脑靶点参与预防、恢复和整体治疗的治疗方法。 改善PPA和其他AD/ADRD的疾病管理。如果不能满足这一需要， 为临床人群提供先进的治疗方法，刻不容缓。父母双方的长期目标 补助金和这种补充是优化失语症的神经康复，无论是由于稳定或进行性 病因学，以及临床上可转化的基于大脑的治疗。该项目的总体目标是加强 通过识别和优化当前项目对卒中诱发性失语症tES的影响（R 01 DC 018282） 在PPA患者中进行脑靶向的连续治疗。这需要神经靶向基础 基于PPA（而不是中风）神经生物学和疾病轨迹。开发的创新管道 父母补助金将与PPA特定的脑靶向选择创新相结合， 它的三个基于共识的变量，以开发基本的tES工具和指导方针。两个具体目标将是 1）为每个PPA变体的完整皮质的靶向调制开发管道和指南;以及 2)使用EEG识别每个PPA变体的tES靶向网络。在第一个目标下， 将开发用于多电极经颅直流电刺激（tDCS）的电场建模的管道， 建模的电场分布的标准数据集也是如此。在第二个目标下，频谱EEG差异 对照组和PPA患者之间的差异将被本地化，为未来的研究奠定基础， 颅内交流电刺激（tACS）。这些贡献将是巨大的，因为预计 资源的开发和共享将提高tES研究的有效性和推理精度， PPA和其他AD/ADRD，支持未来特定于神经调节AD的拨款申请的开发， 在这些急需创新的临床人群中进行辅助治疗。