ANDI – The Australian normative and dementia imaging collaborative network: Software tools for large databases

sults: Immunohistochemical staining of post-mortem brain tissue reveals two major patterns based on the presence of interneuronal inclusions. The first pattern is a build up of tau either in the form of classic Pick bodies, or diffuse neuronal and glial typically seen in patients with mutations of the tau gene. The second major pattern consists of TDP-43 inclusions found in those with MND associated FTD and more recently with patients with progranulin gene mutations. Up to a third of patients have a positive family history and two major causative gene mutations occur on chromosome 17: the microtubule associated protein tau (MAPT) gene and the progranulin gene. Familial motor neuron disease with FTD has been linked to chromosome 9 although no gene is yet identified. Three main variants are recognised. Patients with the behavioural variant present with insidiously progressive changes in personality and behaviour. There is impaired judgement, a lack of initiation and apathy. Social skills deteriorate and there can be socially inappropriate behaviour, disinhibition, obsessive–compulsive and ritualized behaviour. Emotional labiality and mood swings are seen, but psychotic phenomena are rare. Simple bedside cognitive screening tests such as the MiniMental State Examination (MMSE:) are insensitive. Imaging reveals changes in the orbital and mesial frontal cortex and the pathology underlying is very variable. In semantic dementia there is a progressive loss in conceptual knowledge causing anomia and impaired comprehension of words, objects, or faces. Patients are unable to understand less frequent words and fail on a range of semantically based tasks. Repetition of words is normal even though patients are unaware of their meaning. Imaging reveals consistent anterior temporal atrophy and the underlying pathology is TDP-43 positive. In progressive non-fluent aphasia there is a gradual loss of expressive language abilities with impairments in the phonological and grammatical aspects of language production. Repetition of multisyllabic words and phrases is impaired but, in contrast to semantic dementia, word comprehension is well preserved. Imaging if often normal and the pathology is typically tau-positive. Conclusions: The diagnosis of FTD is based on the clinical, neuropsychological, and imaging assessments. There is emerging evidence of some correspondence between clinical phenotype and underlying pathology which has implications for counseling and for prognosis.