Familial Presenile Dementia with Bitemporal Atrophy

Abstract

This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer’s disease.

18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology inMAPTmutation carriers

“…The p.R406W mutation in the gene encoding the tau protein ( MAPT c.1216C>T; R406W) on chromosome 17 results in neurofibrillary tangles that are similar to the neurofibrillary tangles in Alzheimer’s disease at an ultrastructural level (Ghetti et al , 2015). Many cases with this mutation present with slowly progressive episodic memory impairment, which in many ways clinically resembles Alzheimer’s disease (Ostojic et al , 2004; Passant et al , 2004). Previous neuropathological examination of R406W mutation carriers revealed tau-positive neurofibrillary tangles and neurites.…”

Evidence for a Common Founder and Clinical Characteristics of Japanese Families with the MAPT R406W Mutation

“…The R406W mutation in exon 13 of MAPT was previously described in different ethnic backgrounds [6,7,8,9,10,11,12]. The patients with the R406W mutation showed a relatively late onset age with an average of 56 years.…”

The Tau R406W Mutation Causes Progressive Presenile Dementia with Bitemporal Atrophy

“…The visuospatial ability and praxis were preserved after 13 years of illness. CT and MRI showed bilateral temporal lobe atrophy and white matter changes in the frontal lobes [4,5]. Neuropathological data from the pedigree are unfortunately not available to date.…”