Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management

Summary

Patients with behavioural-variant frontotemporal dementia (bvFTD) present with insidious changes in personality and interpersonal conduct that indicate progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation, and decision making. The underlying pathological changes are heterogeneous and are characterised by various intraneuronal inclusions. Biomarkers to detect these histopathological changes in life are becoming increasingly important with the development of disease-modifying drugs. Gene mutations have been found that collectively account for around 10–20% of cases. Recently, criteria proposed for bvFTD define three levels of diagnostic certainty: possible, probable, and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process, with support from neuropsychological testing designed to detect impairment in decision making, emotion processing, and social cognition. Brain imaging is important for increasing the level of diagnostic certainty. A recently developed staging instrument shows much promise for monitoring patients and evaluating therapies, which at present are aimed at symptom amelioration. Carer education and support remain of paramount importance.

Introduction

Frontotemporal dementia (FTD) is the clinical diagnostic term now preferred to describe patients with a range of progressive dementia syndromes associated with focal atrophy of the orbitomesial frontal and anterior temporal lobes.¹ Epidemiological studies suggest that FTD is the second most common cause of young-onset dementia after Alzheimer's disease (AD).2, 3 Two independent studies from the UK revealed a prevalence of around 15 cases per 100 000 population aged 45–64 years (95% CI 8–27 per 100 000).² Although thought to be a rare cause of dementia after age 65 years, FTD might be more common than assumed because older adults rarely undergo the types of investigation needed to establish a confident diagnosis in vivo and are not generally followed to autopsy.

Unlike AD, both the clinical profile and the underlying pathological changes are heterogeneous in FTD. Two broad presentations are recognised: progressive deterioration in social function and personality, known as behavioural-variant FTD (bvFTD), and insidious decline in language skills, known as primary progressive aphasia, which can, in turn, be subdivided according the predominant pattern of language breakdown into progressive non-fluent aphasia and semantic dementia.4, 5, 6 The syndrome of FTD overlaps with motor neuron disease (MND) both clinically and pathologically, and with some of the extrapyramidal motor disorders. Around 10% of patients with FTD develop clinical and neurophysiological evidence of MND,7, 8 and, similarly, patients with MND show behavioural and/or language changes that, in some instances, are severe enough to qualify for a diagnosis of FTD.⁹ Of the extrapyramidal disorders, corticobasal degeneration and progressive supranuclear palsy show substantial overlap with FTD and share the finding of abnormal tau pathology.¹⁰

This is a broad and rapidly evolving field; therefore, in this Review, we have focused on the clinical aspects of bvFTD because there have been recent authoritative reviews of the aphasic syndromes.4, 6 Our aim is to place advances in the diagnosis, staging, and management of bvFTD within the context of recent pathological and genetic discoveries. The assessment of any patient with suspected bvFTD should involve behavioural and neuropsychiatric tests, assessment of everyday abilities, cognitive testing, and neuroimaging. Various blood and CSF biomarkers are under development, but are not yet available for routine clinical application. Genetic testing is advised for those at high risk of a gene mutation (figure 1).¹¹