Frontotemporal dementia
In this chapter by David Perry and Howard Rosen, the clinical syndrome of frontotemporal dementia (FTD) and its underlying pathological etiologies (frontotemporal lobar degeneration (FTLD)) are reviewed. Newly developed diagnostic criteria for FTD have been developed, which identify three core clinical syndromes: (i) behavioral variant FTD (bvFTD), (ii) semantic variant primary progressive aphasia (svPPA, also called semantic dementia), and (iii) nonfluent variant primary progressive aphasia (nfvPPA). The most common presentation is bvFTD, with initial symptoms that might include apathy, disinhibition, loss of empathy, and other personality changes and MRI revealing relative atrophy of the fronto-insular cortex and underlying white matter. Cognitive testing often reveals relative deficits in executive function, although cognition might be relatively preserved early in the disorder. The hallmark features of svPPA include word-finding deficits and loss of semantic knowledge for words and objects, with MRI usually revealing relative atrophy in the left anterior temporal lobe. Bilateral temporal lobe atrophy becomes more prevalent over the course of the disease with additional frontal lobe involvement and behavioral symptoms including loss of empathy, and compulsions might appear (although they are not usually a presenting feature as in bvFTD). Slow and effortful speech is a classic feature of nfvPPA, with frank mutism being common over the course of the disease. MRI typically reveals asymmetric atrophy of the left inferior frontal cortex. Other clinical syndromes, including motor neuron disease (i.e., amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS)), can overlap significantly with FTD syndromes and are referred to as FTD spectrum disorders. The underlying neuropathology of FTD is complex, and research in this field is evolving rapidly. As a general guideline, svPPA tends to be associated with TDP-43 pathology, nfvPPA tends to be associated with tau pathology, and bvFTD is associated with a variety of pathologies (TDP-43, tau, FUS, PSP, and CBD). Treatments for these disorders are currently symptomatic, although clinical trials are in development.