1 Stroke and Dementia Research Centre, St George's, University of London, Cranmer Terrace, London, SW17 0RE UK.
Brain. 2013 Dec;136(Pt 12):3727-37. doi: 10.1093/brain/awt269. Epub 2013 Oct 18.
Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer's disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer's disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer's disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer's disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer's disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer's disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer's disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends over the three stages of disease in syntactic complexity, semantic and lexical content. The findings suggest, first, that there is a progressive disruption in language integrity, detectable from the prodromal stage in a subset of patients with Alzheimer's disease, and secondly that measures of semantic and lexical content and syntactic complexity best capture the global progression of linguistic impairment through the successive clinical stages of disease. The identification of disease-specific language impairment in prodromal Alzheimer's disease could enhance clinicians' ability to distinguish probable Alzheimer's disease from changes attributable to ageing, while longitudinal assessment could provide a simple approach to disease monitoring in therapeutic trials.
尽管间歇性记忆障碍的隐匿病史是阿尔茨海默病的典型表现症状，但详细的神经心理学分析常常显示出其他认知领域的缺陷，包括语言。我们团队的先前研究表明，语言变化可能反映在典型阿尔茨海默病的早期阶段的连贯言语生成中。本研究的目的是确定可用于检查阿尔茨海默病纵向损伤模式的连贯言语特征。从我们的一个纵向衰老和痴呆队列研究的 15 名前参与者中获得了连贯言语样本，在这些参与者中，阿尔茨海默病在生前被诊断，并在死后得到证实。所有患者在转化为可能的阿尔茨海默病之前的 6 至 18 个月内，均符合轻度认知障碍的临床和神经心理学标准。在这些患者的亚组中，获得了神经心理学数据，这些数据既在转化为阿尔茨海默病时获得，也在疾病严重程度从轻度进展到中度时获得。从这些患者中获得了后续疾病阶段的连贯言语样本。使用 Cookie Theft 图片描述任务获取口语语言样本。使用句法复杂性、词汇内容、言语生成、流畅性和语义内容的测量方法对样本进行分析。个体病例分析显示，在阿尔茨海默病的前驱阶段，语言出现了微妙的变化，三分之二的轻度认知障碍患者的连贯言语显示出显著但异质的变化。然而，轻度认知障碍阶段的损伤并不一定意味着在轻度或中度疾病阶段存在缺陷，这表明非语言因素对某些方面的表现有影响。随后对这些措施的检查显示，句法复杂性、语义和词汇内容方面存在显著的线性趋势。研究结果表明，首先，在阿尔茨海默病患者的亚组中，从前驱阶段开始，就存在语言完整性的逐渐破坏，其次，语义和词汇内容以及句法复杂性的测量方法最能捕捉到语言损伤在疾病连续临床阶段的整体进展。在前驱性阿尔茨海默病中识别出特定于疾病的语言损伤，可以增强临床医生区分可能的阿尔茨海默病与归因于衰老的变化的能力，而纵向评估则可以为治疗试验中的疾病监测提供一种简单的方法。
