Rehabilitation of speech and language in primary progressive aphasia

描述(申请人提供)：原发性进行性失语症(PPA)是一种由于支持言语和语言的大脑区域的神经退化而导致的沟通能力的逐渐下降。产后焦虑症是一种毁灭性的疾病，可以影响到50多岁的S这样的成年人，剥夺他们在社会中沟通和发挥作用的能力。在过去的十年里，人们已经很好地描述了PPA的认知和神经基础，并识别了三种主要的变体。在这项工作的基础上，我们现在准备研究基于现代认知和神经解剖学概念的行为治疗。为了在这一独特的患者群体中建立最佳的临床实践，对有效的行为治疗模式的研究是非常必要的。该项目的长期目标是提供循证治疗方法，解决PPA三种变体中每一种的特定认知-语言特征。我们的治疗方法旨在利用与每个PPA综合征保留的解剖回路相关的备用认知功能。在这个框架内，我们将应用现代神经成像技术来确定治疗成功的解剖学预测因素。这项研究有三个主要目标，建立在我们以前工作的基础上：1)评估剂量修改对对数和语义PPA变体中词汇提取的有效治疗的价值；2)建立一种新的治疗不流利/无语法PPA的句法和言语产生的有效性；以及3)确定每种变体对治疗反应的灰质和白质预测因子。为了实现这些目标，我们将招募24名PPA患者，他们将接受全面的多学科评估和神经成像。随后，参与者将参加根据每个变体的认知-语言特征量身定做的行为治疗，并将在治疗后进行长达一年的跟踪，以确定康复的长期效果。这项雄心勃勃的研究和必要的招募将是可能的，因为该项目可以通过加州大学旧金山分校的记忆和衰老中心及其资助的项目获得资源，该中心是PPA研究领域的领先机构。目前的研究将为PPA康复策略的有效性以及面对神经退行性变恢复的解剖学基础提供基本证据，有可能改善这种衰弱疾病患者的临床护理。

DESCRIPTION (provided by applicant): Primary progressive aphasia (PPA) is a gradual decline in communication ability caused by neurodegeneration of brain regions that support speech and language. PPA is a devastating condition that can affect adults as young as their 50's, depriving them of the ability to communicate and function in society. In the past decade, the cognitive and neural bases of PPA have been well characterized and three main variants have been identified. Based on this body of work, we are now poised to investigate behavioral treatments that are grounded in modern cognitive and neuroanatomical concepts. Research into effective modes of behavioral treatment is greatly needed in order to establish best clinical practices in this unique patient population. The long-term objectives of this project are to provid evidence-based treatment methods addressing the specific cognitive-linguistic profiles of each of the three variants of PPA. Our treatment approach is designed to capitalize on spared cognitive functions that are associated with preserved anatomical circuits in each PPA syndrome. Within this framework, we will apply modern neuroimaging techniques to identify anatomical predictors of treatment success. The study has three main goals that build on the findings of our previous work: 1) to assess the value of dose modifications to a proven treatment for lexical retrieval in logopenic and semantic variants of PPA 2) to establish the efficacy of a novel treatment for syntax and speech production in nonfluent/agrammatic PPA, and 3) to determine gray and white matter predictors of response to treatment in each variant. In order to accomplish these aims, we will enroll 24 individuals with PPA, who will undergo a comprehensive multidisciplinary evaluation and neuroimaging. Subsequently, participants will be enrolled in behavioral treatment tailored to the cognitive-linguistic profile of each variant an will be followed for up to a year post-treatment in order to determine long-term effects of rehabilitation. This ambitious study and the necessary recruitment will be possible because of resources available to the project through the UCSF Memory and Aging Center, a leading institution in the field of PPA research, and its funded projects. The current study will provide fundamental evidence regarding the efficacy of rehabilitation strategies in PPA as well as the anatomical bases for recovery in the face of neurodegeneration, with the potential to improve clinical care for individuals with this debilitating condition.