La démence frontotemporale : aspects cliniques et morphologiques

Abstract

Frontotemporal dementia (FTD) includes a heterogeneous group of sporadic and familial neuropsychiatric diseases. Together with dementia with Lewy bodies it is, after Alzheimer's disease, the second most common form of dementia in the presenile age. Unlike the incidence of Alzheimer's disease, which increases with age, frontotemporal dementia only rarely begins after the age of 75 and more often affects people in midlife. Based on consensus guidelines, three distinct clinical entities can be distinguished in frontotemporal dementia: frontotemporal dementia per se, primary progressive aphasia and semantic dementia. The core clinical phenotype of frontotemporal dementia per se consists of gradual and progressive changes in behaviour. The most common presentation is an early change in social behaviour and personal conduct, often associated with lack of inhibition, resulting in impulsive or inappropriate behaviour. In primary progressive aphasia, patients present with troubles in the expression of language, marked by problems using the correct word but with well-preserved understanding of word meaning. With progression of the disease, less and less language is used until the patient is virtually mute (non fluent aphasia). In semantic dementia, patients present with problems naming and understanding word meaning in the context of fluent, effortless and grammatically correct speech output (fluent aphasia). Both types of language disturbance occur in the setting of relative preservation of other cognitive domains, such as memory. All FTD patients have in common a circumscribed cortical atrophy of the frontal and/or the anterior temporal lobes although variations in the anatomical distribution of the pathology largely determine the associated clinical syndromes just mentioned. Pathologically, Pick's disease, corticobasal degeneration and familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) have been reported as the histological substrate of frontotemporal dementia. However, dementia of the frontal type and the motor neuron disease inclusion dementia (MNDID) are the most frequent neuropathological subtypes of frontotemporal dementia. Both are characterised by neuronal loss, astrocytic gliosis, laminar spongiosis affecting cortical laminae I-III and, in some cases, by an astrocytic gliosis and a cell loss in the striatum, the thalamus and the substantia nigra. Motor neuron disease inclusion dementia is further defined by the presence of characteristic ubiquitin-containing intracytoplasmic inclusions in granule cells of the dentate gyrus and in the cell somata and neurites of superficial neocortical neurons. By immunohistochemistry, these inclusions are found to react with anti-ubiquitin antibodies but not with antibodies to tau protein. However, the nature of the associated protein accumulating with ubiquitin in this disorder remains elusive. The recent finding of familial cases of frontotemporal dementia with ubiquitin-positive but tau-negative neuronal inclusions suggests that there might be a genetic background to this type of pathological process. In contrast to dementia of the frontal type and to motor neuron disease inclusion dementia, Pick's disease, corticobasal degeneration and FTDP-17 are characterised by abundant filamentous nerve cell inclusions made of the microtubule-associated protein tau.