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

痴呆症是一种复杂和多方面的临床状态，其在脑病理学的生物学机制和分子结构以及这些病理学对脑功能的影响方面显示出显著的变化。重要的是，并非所有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病理学），并且并非所有人都将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从选择性理解困难和/或产生言语和语言开始的-这种模式被称为原发性进行性失语症（PPA）。由于语言是一种复杂的心理能力，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，人们认识到三种不同的模式。有些患者会出现理解单词或物体意义的能力下降（“语义性痴呆”），而另一些患者的问题在于单词和句子的产生（“进行性非流利性失语症”）。第三组表现出较轻的问题，沿着明显的不能重复口语句子（“逻辑缺失性进行性失语症”）。在病理学水平上，这三种痴呆综合征远非不同，使得它们的生物学基础在生活中难以确定。提高认识应该会导致疾病特异性治疗的发展，但由于其相对罕见（不到5%的痴呆病例开始与PPA），临床试验将需要大规模的国际合作，这些将不可避免地包括讲英语以外的语言的患者。在主要影响语言本身的情况下，语言社区的这种多样性显然会带来问题。因此，该项目的主要目的是为共同的描述性货币奠定基础，其中可以描述三种类型的PPA，并以相同的尺度量化患者的能力，而无论评估时使用何种语言。为了实现这一目标，我们将开发一个简单的语言评估工具，这将允许三个PPA综合征在一套共同的标准上相互区分，并使用同等的严重程度进行长期监测。鉴于简易精神状态检查（MMSE）在定义和量化痴呆症方面的全球影响和重要性，这种简短的语言测试将被称为简易语言状态检查（或“MLSE”）。该工具的目的是全面而简短，并能够由临床医生管理，没有特殊的语言评估专业知识。试图同时为世界上所有主要语言开发MLSE版本是不现实的，因此我们将集中精力开发两种欧洲语言：英语和意大利语，这两种语言分别是大约3.6亿和6000万人的母语。我们将确保MLSE出现的分类与专家临床医生目前认可的分类相同，通过验证专家临床意见和卒中后患者失语症的模式来验证该测试。我们还将在已知与每个变体相关的MR成像表现中寻找验证。当英语和意大利语版本的仪器已经完全开发和验证，我们将从运动相关的神经退行性疾病（如帕金森病）患者人群中收集更多的数据，以更深入地了解这些疾病对大脑的影响，并确定患者的生活质量可以通过康复来改善的方式。

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.