The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry

Abstract

The primary goal of this article is to critically discuss the syndromic overlap that exists between early behavioural variant frontotemporal dementia (bvFTD)--the most common clinical syndrome associated with frontotemporal lobar degeneration (FTLD)--and several primary psychiatric disorders. We begin by summarising the current state of knowledge regarding FTLD, including the recent discovery of FTLD-causative genetic mutations. Clinicopathological correlations in FTLD are subsequently discussed, while emphasising that clinical syndromes of FTD are dictated by the distribution of FTLD pathology in the brain. We then review a large number of cases with suspected and confirmed bvFTD that had previously been diagnosed with a primary psychiatric disorder. The clinical and neuroscientific implications of this overlap are discussed, focusing on the importance of early diagnosis for clinical and therapeutic reasons. We propose that largely due to the paucity of biomarkers for primary psychiatric disorders, and the limited use of FTLD-related biomarkers by psychiatrists at present, it is very difficult to separate patients with early bvFTD from those with primary psychiatric disorders based on clinical grounds. Furthermore, specific limitations of the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria for bvFTD may inadvertently discourage recognition of bvFTD in mental health settings. Clinically, more research is needed to develop tools that allow early differentiation of bvFTD from primary psychiatric disease, as bvFTD therapies will likely be most effective in the earliest stages of disease. From a neuroscience perspective, we argue that bvFTD provides an excellent paradigm for investigating the neural basis of psychiatric disorders.

Keywords: BEHAVIOURAL DISORDER; DEMENTIA; FRONTAL LOBE; NEUROPSYCHIATRY; PSYCHIATRY.

Figure 1

Lateral (A and C) and medial (B and D) views of the right hemisphere of a male patient with behavioural variant frontotemporal dementia (bvFTD) due to frontotemporal lobar degeneration (FTLD) τ-Pick’s disease (A and B) compared to an age-matched normal brain (C and D) (A and C were flipped for easier comparison). The dorsolateral prefrontal cortex (DLPFC) is seen on the lateral surface of the brain, anterior to the primary motor and premotor cortices (indicated by yellow stars above) in the frontal lobe. In a normal brain (C), the volume of cortical gyri (folds) and the width of sulci (grooves) of the DLPFC are roughly equal to those of gyri and sulci in more posterior brain regions. In the affected brain (A) there is prominent atrophy (volume loss) of gyri within the DLPFC, leading to widening of sulci compared to more posterior brain regions; this atrophy pattern is striking when compared to the DLPFC of the normal brain (C). A similar degree of atrophy can be seen on the medial/mesial surface of the frontal lobe of the affected brain (B) compared to the normal brain (D); the affected brain shows prominent atrophy of the anterior cingulate gyrus (blue stars) and superior frontal gyrus (red stars), as well as the orbitofrontal cortex (pink stars).

Figure 2

Brain MRI T1 of the patient presented in figure 2 7 years before death due to frontotemporal lobar degeneration (FTLD) τ-Pick’s disease (A–C) compared to an age-matched normal control (D–F). There is prominent atrophy of the orbitofrontal cortex seen on axial T1 images (A); note prominent widening of the olfactory sulcus (A, white arrow) compared to normal (D). There is also prominent atrophy of the mesial frontal lobes seen on axial T1 images (B), as indicated by space between yellow arrowheads, compared to normal (E). On sagittal views, there is significant atrophy of the superior frontal gyrus and anterior cingulate gyrus (C) compared to normal (F).