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

描述(申请人提供)：当今许多工业化国家面临的最重大的公共卫生挑战之一涉及阿尔茨海默氏症和相关痴呆的管理。尽管分子生物学的进步有望识别药物靶点，从而减缓几种形式的痴呆症的进展，但我们的医疗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，尤其是对于语言和人类交流的进行性障碍，其中许多反映了概念知识(即语义记忆)的丧失。到目前为止，理论上原则性的语言干预痴呆症的发展受到两个因素的限制。首先，神经科学缺乏对局部脑损伤如何影响人类语义记忆的组织和完整性的统一理解。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。我们试图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检查语言保持的可能性，同时我们将在一个由大约100个单词组成的精心制作的个性化微词典上培训阿尔茨海默病和语义性痴呆患者。患者将通过重复命名和语义特征生成相结合的方式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，它保护有限的词典免受损失，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重复使用综合认知电池来检验局部大脑灰质、神经心理表现和语言记忆随时间的相关性。具体目标2代表了对阿尔茨海默病和语义性痴呆中命名障碍机制的性质的补充调查。我们将调查视觉搜索组织的几个方面，因为参与者说出训练过的和未训练过的图片。眼球追踪的高时间分辨率将对这些患者群体中视觉搜索模式、命名准确性和潜在治疗效果之间的关系产生重要的洞察力。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。我们将在一个更广泛的语义组织模型的背景下将这些目标联系起来，该模型将这些临床人群中的语义损害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.