A standardised, multilingual, Mini Linguistic State Examination (MLSE) for classifying and monitoring Primary Progressive Aphasia

痴呆是一种复杂的、多方面的临床状态，在脑病理的生物学机制和分子结构以及这些病理对脑功能的影响方面表现出显著的差异。重要的是，并不是所有的痴呆症患者都患有阿尔茨海默病(尽管这仍然是最常见的潜在疾病)，也不是所有的人都会经历健忘作为精神困难的第一个迹象。近年来被广泛研究的一种痴呆症表现是一种以理解和/或产生言语和语言的选择性困难开始的类型--一种被称为原发性进行性失语(PPA)的模式。由于语言是一种如此复杂的心理能力，依赖于许多广泛分布的大脑区域，PPA可以采取多种形式。目前，人们认识到了三种截然不同的模式。一些患者体会到理解单词或物体意义的能力降低(“语义痴呆”)，而在另一些患者中，问题出在单词和句子的产生上(“渐进性非流利性失语”)。第三组出现的问题较轻，并且无法重复口语句子(对数进行性失语症)。在病理学层面上，这三种痴呆症证候相去甚远，难以在生活中确定其生物学基础。提高对疾病的了解应该会导致疾病特效性治疗的发展，但由于它们相对罕见(不到5%的痴呆症病例以PPA开始)，临床试验将需要大规模的国际合作，这些合作将不可避免地包括说英语以外的语言的患者。这种语言社区的多样性显然会在主要影响语言本身的情况下带来问题。因此，这个项目的主要目标是为共同的描述性货币奠定基础，在这种货币中，可以描述三种类型的PPA，并在相同的尺度上量化患者的能力，无论他们被评估的语言是什么。为了实现这一目标，我们将开发一种简短的语言评估工具，允许根据一套共同的标准区分三种PPA综合征，并使用相同的严重程度随着时间的推移进行监测。鉴于微型智力状态检查(MMSE)在定义和量化痴呆症方面的世界性影响和重要性，这项简短的语言测试将被命名为微型语言状态检查(MLSE)。该仪器的目的是全面而简短的，并能够由临床医生使用，而不是在语言评估方面有专门的专业知识。试图同时开发世界上所有主要语言的MLSE版本是不现实的，因此我们将专注于两种欧洲语言：英语和意大利语，这两种语言分别约有3.6亿人和6000万人。我们将确保MLSE产生的分类与专家临床医生目前认可的分类相同，方法是对照专家的临床意见和中风后患者患失语症的模式来验证测试。我们还将在已知与每种变异相关的磁共振成像表现中寻找验证。当英语和意大利语版本的仪器完全开发和验证后，我们将从与运动相关的神经退行性疾病(如帕金森氏病)患者群体中收集更多数据，以便更深入地了解这些疾病组对大脑的影响，并确定通过康复可以提高患者生活质量的方法。

Dementia is a complex and multifaceted clinical state, which shows marked variations in the biological mechanisms and molecular structure of brain pathology, and in the effects that these pathologies have on brain function. Importantly, not all people with dementia are suffering from Alzheimer's disease (though this remains the commonest underlying pathology), and not all experience forgetfulness as the first sign of mental difficulty. One type of dementia presentation that has been extensively studied over recent years is one that begins with selective difficulty understanding and/or producing speech and language - a pattern known as primary progressive aphasia (PPA). Because language is such a complex mental ability, and relies on a number of widely distributed brain areas, PPA can take a variety of forms. Currently, three distinct patterns are recognised. Some patients experience a reduced ability to appreciate the meaning of words or objects ('semantic dementia'), while in others the problems lie in the production of words and sentences ('progressive nonfluent aphasia'). A third group displays milder problems, along with a striking inability to repeat spoken sentences ('logopenic progressive aphasia'). At the level of pathology these three dementia syndromes are far from distinct, making their biological basis difficult to determine during life. Improved understanding should lead to the development of disease specific treatments, but because of their relative rarity (less than 5% of cases of dementia begin with PPA), clinical trials will necessitate large scale, international collaborations, and these will inevitably include patients who speak languages other than English. Such a diversity of language communities will obviously present problems in the context of a condition that primarily affects language itself. The principal aim of this project, therefore, is to lay the foundations of a common descriptive currency, in which the three types of PPA can be described, and patients' abilities quantified on the same scale, regardless of the language in which they are assessed. To achieve this, we will develop a brief language assessment instrument, which will allow the three PPA syndromes to be distinguished from one another on a common set of criteria and monitored over time using equivalent levels of severity. In view of the worldwide impact and importance of the Mini Mental State Examination (MMSE) in defining and quantifying dementia more generally, this brief language test will be given the title of the Mini Linguistic State Examination (or 'MLSE'). The instrument is intended to be comprehensive yet brief, and capable of being administered by clinicians without special expertise in language assessment. It would be unrealistic to try to develop versions of the MLSE for all the world's major languages at once, so we will concentrate on two European languages: English and Italian, the native languages of around 360 million and 60 million people, respectively. We will ensure that the same classifications emerge from the MLSE as are currently recognized by expert clinicians by validating the test against expert clinical opinion, and against the patterns of aphasia suffered by patients following a stroke. We will also look for validation in the MR imaging appearances that are known to be associated with each variant. When English and Italian versions of the instrument have been fully developed and validated, we will gather additional data from populations of patients with movement related neurodegenerative disorders (such as Parkinson's disease) in order to gain deeper insights into the effects of these groups of disorders on the brain, and to identify ways in which sufferers' quality of life can be improved through rehabilitation.