Primary Progressive Aphasia: Neural Bases and Rehabilitation

描述（由申请人提供）：原发性进行性失语症（PPA）是由影响语言皮层的神经退行性疾病引起的语言技能逐渐下降。PPA患者的口语和书面语言障碍的典型模式已经在文献中描述（Gorno-Tempini et al.，2004; Hodges等人，1992; Neary等人，1998年）;然而，在特定的语言领域的赤字的神经和认知基础是一个值得进一步调查的领域。此外，PPA患者目前没有得到临床专业人员的推荐和服务，包括语言病理学家。事实上，PPA中观察到的语言障碍的行为治疗的效用还有待系统地探索。这个为期三年的项目的长期目标是描述PPA患者语言下降的认知和神经解剖学基础，并研究每种PPA变体中语言治疗的效用。具体而言，该项目的目的是探讨灰色和白色物质异常和PPA的关键语言域的损害之间的关系，以评估实用的理论动机的行为治疗与障碍的个人词汇检索，并检查解剖和行为预测语言治疗的反应。为了实现这些目标，30名PPA患者和30名正常对照者将接受一项全面的语言测试，包括句法、语义、语音和正字法领域的测试。将使用基于体素的形态测量（VBM）和弥散张量成像（DTI）评价区域灰质萎缩和白色束完整性，这些成像测量将与复合语言测量相关。此外，PPA的每个诊断变体中的五个人将被给予独特的治疗方案，该方案旨在利用备用的认知过程，同时试图补救和/或补偿受损的过程。将通过检查训练和未训练项目和任务的表现，以及通过评估完成结构化治疗后的维持情况，来表征每个PPA变体中对行为治疗的反应。最后，治疗前的措施，灰色和白色物质的完整性，以及模式的表现对复合语言措施将检查相对于治疗的反应。这些分析将为PPA患者的神经解剖损伤与其语言特征和对行为治疗反应能力之间的关系提供重要证据。 公共卫生相关性：该项目与公共卫生的相关性源于其提供有关原发性进行性失语症的性质和治疗的关键信息的能力，并有可能加强这种衰弱性疾病患者的临床管理和康复。

DESCRIPTION (provided by applicant): Primary progressive aphasia (PPA) is a gradual decline in language skills that results from neurodegenerative disease affecting language cortex. The typical patterns of spoken and written language impairments in individuals with PPA have been characterized in the literature (Gorno-Tempini et al., 2004; Hodges et al., 1992; Neary et al., 1998); however, the neural and cognitive bases for deficits in specific language domains are an area that warrants further investigation. In addition, individuals with PPA are currently under-referred and underserved by clinical professionals, including speech-language pathologists. In fact, the utility of behavioral treatment for the language impairments observed in PPA has yet to be systematically explored. The long-term goals of this three-year project are to characterize the cognitive and neuro anatomical bases for language decline in individuals with PPA and also to examine the utility of language treatment in each of the PPA variants. Specifically, the project aims to explore the relation between gray and white matter abnormalities and impairment to critical language domains in PPA; to assess the utility of theoretically motivated behavioral treatment for lexical retrieval in individuals with the disorder; and to examine anatomical and behavioral predictors of response to language treatment. In order to accomplish these aims, 30 individuals with PPA and 30 normal controls will be administered a comprehensive language battery comprising tests in the domains of syntax, semantics, phonology, and orthography. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) will be used to evaluate regional gray matter atrophy and white matter tract integrity and these imaging measures will be correlated with composite language measures. In addition, five individuals in each diagnostic variant of PPA will be administered a unique treatment protocol designed to capitalize on spared cognitive processes while attempting to remediate and/or compensate for impaired processes. Response to behavioral treatment in each PPA variant will be characterized by examining performance on trained and untrained items and tasks and by assessing maintenance following completion of structured treatment. Finally, pre-treatment measures of gray and white matter integrity as well as patterns of performance on composite language measures will be examined relative to response to treatment. These analyses will provide important evidence regarding the relation between neuro anatomical damage in PPA patients and their language characteristics and ability to respond to behavioral treatment. PUBLIC HEALTH RELEVANCE: This project's relevance to public health stems from its capacity to provide critical information regarding the nature and treatment of primary progressive aphasia, with the potential to enhance clinical management and rehabilitation of individuals with this debilitating disorder.