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

项目总结/摘要 当今许多工业化国家面临的最重大的公共卫生挑战之一是， 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 承诺确定药物靶点，将减缓几种形式的痴呆症的进展，我们的医疗保健 系统在有效治疗认知和语言的宏观缺陷方面的能力仍然有限。这是 尤其是在语言和人类交流的进行性障碍方面，其中许多 反映概念知识的损失（即，语义记忆）。到目前为止，理论上- 针对痴呆症的原则性语言干预受到两个因素的限制。首先，神经科学缺乏 对区域性脑损伤如何影响人类组织和完整性的理解 语义记忆其次，传统的神经心理康复方法假设学习是 在进行性记忆障碍的情况下是不可能的。我们力求通过以下方式克服这些局限性： 两个具体目标。在具体目标1中，我们将研究两年以上语言保持的潜力 在我们训练阿尔茨海默病和语义性痴呆患者的过程中， 一个由大约100个单词组成的个性化微词典。患者将在这种高度受限的 通过重复命名和语义特征生成相结合的方法来生成词汇。这种治疗方法是 它的独特之处在于，它保护有限的词汇免受损失，而不是像疾病一样训练被遗忘的概念。 严重程度我们将研究局部大脑灰质，神经心理， 通过前/后结构神经成像和重复的 一个全面的认知电池的管理。具体目标2是一项补充调查 阿尔茨海默病和语义学中命名障碍的机制的本质 痴呆我们将调查视觉搜索组织的几个方面， 未经训练的图片眼动追踪的高时间分辨率将产生对关系的重要见解 视觉搜索模式、命名准确性和这些患者的潜在治疗效果之间的关系 人口。我们还将把这些观察到的视觉搜索模式与区域性灰质萎缩联系起来。 我们将把这些目标置于一个更广泛的语义组织模型的上下文中， 这些临床人群的语义障碍和学习模式。

PROJECT SUMMARY/ABSTRACT 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.