A new framework for conceptualizing symptoms in frontotemporal dementia: From animal models to the clinic

Abstract

Behavioural-variant frontotemporal dementia is characterized by a number of ostensibly disparate clinical features, which have largely been considered independently. This update proposes an integrated conceptual framework for these symptoms, by bringing together findings from animal studies, functional neuroimaging and behavioural neurology. The combined evidence indicates that many of the clinical symptoms-such as altered eating behaviour; overspending and susceptibility to scams; reduced empathy and socially inappropriate behaviour; apathy and stereotyped/ritualistic behaviour-can be conceptualized as a common underlying deficiency in goal-directed behaviour and the concomitant emergence of habits. This view is supported by similarities between the characteristic patterns of frontostriatal and insular atrophy in behavioural-variant frontotemporal dementia and the circuitry of homologous brain regions responsible for goal-directed and habitual behaviour in animals. Appreciating the impact of disturbance in goal-directed behaviour provides a new, integrated understanding of the common mechanisms underpinning prototypical clinical symptoms in behavioural-variant frontotemporal dementia. Furthermore, by drawing parallels between animal and clinical research, this translational approach has important implications for the development and evaluation of novel therapeutic treatments, from animal models through to behavioural interventions and clinical trials in humans.