Neurobehavioral features of frontotemporal dementia
What are the neurobehavioral characteristics of frontotemporal dementia (FTLD) ?
Frontotemporal dementia (FTLD) is a heterogeneous group of disorders that is variable in clinical presentation and has several different associated pathologic findings.
FTLD is typically divided into three clinical syndromes: behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA or PPA).
BvFTD typically has a behavioral onset, which can be primarily orbitofrontal (disinhibited), primarily dysexecutive, or primarily medial dorsal (psychomotor retardation and apathy) in character.
SD and PNFA have language onsets (see below).
All three have an earlier age of onset (average 55 years), a more rapid progression, and a higher genetic susceptibility (40% familial) than AD. In early-onset dementia, its frequency is equal to AD.
Corticobasal syndrome and progressive supranuclear palsy are two related diseases that are not classified as FTD but often share some symptoms with FTD.
They can also be due to mutations in the same genes as FTD. FTD can also occur in conjunction with amyotrophic lateral sclerosis (ALS) (FTD/ALS).
Pathologically, FTD is associated with several different findings in limbic, paralimbic, temporal, and anterior frontal regions: neurofibrillary tangles (tau pathology), Pick bodies (tau pathology), fused in sarcoma inclusions (FUS), Tar DNA binding protein-43 inclusions (TDP-43), and rarely changes without distinctive histopathology.
It is somewhat difficult to correlate a specific clinical syndrome with the underlying pathology, but FTD/ALS and SD are both highly associated with ubiquitin and TDP-43 inclusions.
Five genetic mutations have thus far been identified in familial FTD. The most common are mutations in the tau ( MAPT ) and progranulin ( PGRN ) genes on chromosome 17.
