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.