Rehabilitation of speech and language in primary progressive aphasia

描述（由申请人提供）：原发性进行性失语症（PPA）是由支持言语和语言的大脑区域的神经变性引起的沟通能力逐渐下降。PPA是一种毁灭性的疾病，可以影响50多岁的成年人，剥夺他们在社会中沟通和发挥作用的能力。在过去的十年中，PPA的认知和神经基础已经得到了很好的表征，并确定了三个主要的变体。基于这些工作，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，非常需要对行为治疗的有效模式进行研究。该项目的长期目标是提供基于证据的治疗方法，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种PPA综合征中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影像学技术，以确定治疗成功的解剖预测。这项研究有三个主要目标，建立在我们以前的工作的结果：1）评估剂量修改的价值，以证明治疗的词汇检索的逻辑和语义变体的PPA 2）建立一种新的治疗的疗效，句法和语音生产nonfluent/agrammatic PPA，和3），以确定灰色和白色物质的预测反应，在每个变量的治疗。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，参与者将参加针对每个变体的认知语言特征的行为治疗，并将在治疗后随访长达一年，以确定康复的长期影响。这项雄心勃勃的研究和必要的招聘将是可能的，因为通过UCSF记忆和衰老中心，在PPA研究领域的领先机构，及其资助的项目提供给该项目的资源。目前的研究将提供有关PPA康复策略疗效的基本证据，以及面对神经退行性变恢复的解剖学基础，有可能改善这种衰弱状况的个人的临床护理。

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.