Progressive Aphasia Cognition Anatomy and Progression

描述（由申请人提供）：言语和语言障碍往往是神经退行性疾病的首发表现，如额颞叶变性、皮质基底变性和阿尔茨海默病。当缺陷局限于语言症状至少两年时，称为原发性进行性失语症。在疾病的第一阶段，对患者的语言、认知和解剖特征的描述可以为早期诊断症状的潜在病因提供关键信息。然而，在痴呆症诊所很少评估言语和语言功能。此外，原发性进行性失语症的大规模、纵向临床和神经影像学研究的数据还不能帮助指导临床医生。在这项研究中，我们建议对200多名原发性进行性失语症患者的语言和解剖学特征进行详细的五年纵向调查。由于加州大学旧金山分校记忆和衰老中心在非典型和早发性痴呆方面有一个国际知名的研究项目，所以这个大型队列研究将成为可能。一般的神经心理学，神经学，功能和大多数神经影像学数据也将作为记忆和衰老中心其他正在进行的项目的一部分收集。我们将结合现代认知和神经影像学分析技术，分离出在进行性失语症中受到影响的言语和语言系统的子成分及其相应的解剖损伤部位。我们对40名患者的初步数据已经表明，特定的言语和语言缺陷与脑萎缩的显著局灶性模式相对应。我们还将跟踪疾病的进展五年，并应用统计模型来研究语言和解剖特征的变化如何相互关联，与功能损害的变化以及研究期结束时的病因诊断。从这项研究中收集的证据将增加我们对言语和语言功能的神经基础的认识，并为早期治疗最有效的神经退行性疾病的诊断提供关键数据。

DESCRIPTION (provided by applicant): Speech and language impairments can often be the first manifestation of neurodegenerative diseases such as frontotemporal lobar degeneration, corticobasal degeneration and Alzheimer's disease. When the deficits remain limited to language symptoms for at least two years, the term primary progressive aphasia applies. Characterization of the linguistic, cognitive and anatomical features of patients in this first stage of the diseases could provide critical information for early diagnosis of the underlying etiology of the symptoms. However, speech and language functions are rarely assessed in the setting of dementia clinics. Moreover, data from large-scale, longitudinal clinical and neuroimaging studies of primary progressive aphasia have not been available to help guide clinicians. In this study, we propose to perform a detailed, five-year longitudinal investigation of the linguistic and anatomical features of over 200 patients with primary progressive aphasia. This large cohort will be possible because the UCSF Memory and Aging Center has an internationally renowned program of research in atypical and early-onset dementias. General neuropsychological, neurological, functional and most neuroimaging data will also be collected as part of other ongoing projects at the Memory and Aging Center. We will combine modem cognitive and neuroimaging analysis techniques to isolate the subcomponents of the speech and language system that are affected in progressive aphasia and their corresponding sites of anatomical damage. Our preliminary data from 40 patients already show that specific speech and language deficits correspond to remarkably focal patterns of brain atrophy. We will also follow the progression of the disease for five years, and apply statistical models to investigate how changes in language and anatomical features correlate with each other, with changes in functional impairment and with etiological diagnosis at the end of the study period. Evidence gathered from this research will increase our knowledge about the neural basis of speech and language functions and provide crucial data for the diagnosis of neurodegenerative diseases in their early stages, when treatment can be most effective.