Published online by Cambridge University Press: 05 August 2016
Historically, classification schemas for degenerative dementias were framed around the clinical and pathological phenomenology of the illness. With improved understanding of the molecular basis for many degenerative conditions, traditional taxonomies are being replaced by molecule-based schemas. Nowhere has this transition been more evident than with frontotemporal dementia (FTD) where, until recently, FTD (or Pick's disease) was used to define a group of patients with selective degeneration of frontotemporal cortex in whom Alzheimer's disease (AD) pathology was absent. With the discovery of tau exon mutations (Poorkaj et al., 1998; Spillantini & Goedert, 1998; Clark et al., 1998) and intron mutations (Hutton et al., 1998) in familial cases with selective frontotemporal degeneration, a clinical/pathological syndrome suddenly had a well-defined molecular and genetic basis. This work clarified the importance of tau protein in the pathogenesis of both sporadic and familial FTD and many hoped that this would lead to a molecule-based diagnostic schema for FTD. However, not all cases with tau pathology have selective frontotemporal anatomic involvement and there are many patients with selective frontotemporal degeneration in whom tau pathology is absent (Kertesz et al., 2000). This has left the field somewhat in limbo with many patients falling in between clinical, pathological or molecule-based diagnostic criteria. Thus, although new insights about abnormalities in tau metabolism are an important piece of the FTD story, it is clear that other factors contribute to producing the clinical syndrome that is recognizable as FTD.
Despite still unresolved issues related to nomenclature, FTD represents an important disorder with distinctive epidemiology, genetics, neuropathology, clinical features and treatment. Importantly, it is possible to diagnose most FTD patients during life (Lopez et al., 1999) and to differentiate them from patients with AD. Because FTD has a distinctivepattern or brain degeneration, it offers many clues to the function of the frontal and anterior cortical regions.
Terminology and epidemiology
In recent years FTD has been recognized as a common cause for degenerative dementia. However, in many clinical settings FTD is rarely, if ever, diagnosed. One problem limiting its recognition is that many patients present with psychiatric symptoms (Gustafson, 1993; Lesser et al., 1989) and do not develop a dementia until much later in the course of their illness. Persistent variability in the diagnostic accuracy and diagnostic suspicion from site to site has compounded the confusion related to the epidemiological features of FTD.