Semantic Memory and Language Learning in Alzheimer's Disease and Semantic Dementi

描述（由申请人提供）：当今许多工业化国家面临的最重要的公共卫生挑战之一涉及阿尔茨海默病和相关痴呆症的管理。尽管分子生物学的进步让我们有希望找到减缓几种痴呆症进展的药物靶点，但我们的医疗保健系统在有效治疗认知和语言宏观缺陷方面的能力仍然有限，尤其是在语言和人类交流的进行性障碍方面，其中许多反映了概念知识（即语义记忆）的丧失。迄今为止，痴呆症的理论原则语言干预的发展受到两个因素的限制。首先，神经科学缺乏对区域脑损伤如何影响人类语义记忆的组织和完整性的连贯理解。其次，传统的神经心理康复方法认为，在进行性记忆障碍的情况下，学习是不可能的。我们力求通过两个具体目标来克服这些限制。在具体目标1中，我们将在两年的时间里对阿尔茨海默病和语义性痴呆患者进行训练，训练他们使用精心制作的、个性化的大约100个单词的微词典，从而研究语言维护的潜力。患者将通过重复命名和语义特征生成的组合来训练这种高度受限的词汇。这种治疗方法的独特之处在于，它可以保护有限的词汇免受损失，而不是随着疾病严重程度的恶化而临时训练被遗忘的概念。我们将通过前/后结构神经成像和反复使用综合认知电池来检查区域脑灰质、神经心理表现和语言保留之间的相关性。特异性目标2代表了对阿尔茨海默病和语义性痴呆中命名障碍机制本质的补充研究。我们将调查视觉搜索组织的几个方面，参与者命名训练过的和未训练过的图片。眼动追踪的高时间分辨率将对这些患者群体的视觉搜索模式、命名准确性和治疗的潜在效果之间的关系产生重要的见解。我们还将把这些观察到的视觉搜索模式与区域灰质萎缩联系起来。我们将把这些目标放在一个更广泛的语义组织模型的背景下，这个模型将这些临床人群的语义损伤和学习模式联系起来。

DESCRIPTION (provided by applicant): One of the most significant public health challenges facing much of the industrialized world today involves the management of Alzheimer's Disease and associated dementias. Although advances in molecular biology hold promise for identifying drug targets that will slow the progression of several forms of dementia, our healthcare system remains limited in its capacity to effectively treat macro-scale deficits in cognition and language This is especially true with respect to progressive disorders of language and human communication, many of which reflect the loss of conceptual knowledge (i.e., semantic memory). To date, the development of theoretically-principled language interventions for dementia has been limited by two factors. First, neuroscience lacks a cohesive understanding of how regional brain damage impacts the organization and integrity of human semantic memory. Second, traditional neuropsychological rehabilitation approaches assume that learning is not possible in the context of progressive memory disorders. We seek to overcome these limitations through two specific aims. In Specific Aim 1, we will examine the potential for language maintenance over a two year period as we train patients with Alzheimer's Disease and Semantic Dementia on a carefully-crafted, personalized micro-lexicon consisting of approximately 100 words. Patients will train on this highly constrained vocabulary via a combination of repeated naming and semantic feature generation. This treatment approach is unique in that it protects a finite lexicon against loss rather than training forgotten concepts ad hoc as disease severity worsens. We will examine correlations between regional cerebral gray matter, neuropsychological performance, and language retention across time via pre/post structural neuroimaging and repeated administration of a comprehensive cognitive battery. Specific Aim 2 represents a complementary investigation of the nature of the mechanisms underlying naming impairment in Alzheimer's Disease and Semantic Dementia. We will investigate several aspects of visual search organization as participants name trained and untrained pictures. The high temporal resolution of eyetracking will yield essential insights into the relationships between visual search patterns, naming accuracy, and potential effect of treatment in these patient populations. We will also correlate these observed patterns of visual search with regional gray matter atrophy. We will contextualize these aims within the context of a broader model of semantic organization that correlates patterns of semantic impairment and learning in these clinical populations.