Primary Progessive Aphasia: Cognition, Anatomy and Progression

言语和语言缺陷通常是神经退行性疾病的最初症状，例如 额颞叶变性、皮质基底节变性和阿尔茨海默病。当演讲和 如果语言缺陷至少持续两年，则适用术语<$primary progressive aphasia <$（PPA）。 在疾病的初始阶段对语言障碍的表征可以提供关键信息 早期鉴别诊断。然而，言语和语言功能很少被评估的设置， 痴呆症诊所，机会往往会失去。此外，来自大规模纵向临床和 PPA的神经影像学研究无法指导临床医生进行诊断、预后和 治疗决定。 我们提出了一个详细的，为期四年的纵向研究的语言，解剖和病理特征， 超过200例原发性进行性失语症患者。这一大型队列的累积将是可能的，因为 加州大学旧金山分校记忆和衰老中心是美国国立卫生研究院资助的非典型和早发性 痴呆症该计划还将提供一般神经心理学，神经学，神经病理学和 大多数神经成像数据。在aim 1中，我们将详细的语言测试分数与区域灰质相关联 在目标2中，扩散张量成像和功能MRI将用于研究结构性改变。 和功能连接的语言网络在PPA;在目标3中，我们将关联死后 组织病理学和体内皮质淀粉样蛋白结果与纵向临床，认知和解剖数据， 发现每种神经退行性疾病的典型进展模式。 从这项研究中收集的证据将增加我们对语音神经基础的了解， 语言功能，并为神经退行性疾病的早期诊断提供重要数据。 阶段，治疗最有效的阶段

Speech and language deficits are often the very first symptoms of neurodegenerative diseases, such as frontotemporal lobar degeneration, corticobasal degeneration and Alzheimer¿s disease. When speech and language deficits remain isolated for at least two years, the term ¿primary progressive aphasia¿ (PPA) applies. Characterization of the linguistic impairments in this initial stage of the disease can provide critical information for early differential diagnosis. However, speech and language functions are rarely assessed in the setting of dementia clinics and the opportunity is often lost. Moreover, data from large-scale longitudinal clinical and neuroimaging studies of PPA are not available to guide clinicians in making diagnostic, prognostic and therapeutic decisions. We propose a detailed, four-year longitudinal study of the linguistic, anatomical and pathological features of over 200 patients with primary progressive aphasia. The accrual of this large cohort will be possible because the UCSF Memory and Aging Center is the site of an NIH-funded research program in atypical and early-onset dementias. This program will also provide general neuropsychological, neurological, neuropathological and most neuroimaging data. In aim 1 we will correlate scores in detailed language tests and regional gray matter volumes; in aim 2 diffusion tensor imaging and functional MRI will be used to investigate alteration in structural and functional connectivity in the language network in PPA; and in aim 3 we will associate post-mortem histopathological and in-vivo cortical amyloid findings with longitudinal clinical, cognitive and anatomical data to find patterns of progression typical of each neurodegenerative disease. 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