Frontotemporal degeneration has prevalence between 15 and 22 cases per 100,000 in the 45- to 64-year-old age range, and incidence ranges from 1.6 to 4.1 cases per 100,000 (21). It is the second most common form of neurodegenerative dementia in younger people. The socioeconomic burden per patient exceeds that due to Alzheimer disease (Galvin et al 2017). Initial presentation can include insidious changes in a person’s personality and behavior or a slowly evolving aphasia syndrome. Parkinsonian and motor neuron symptoms may also occur, either initially or as the disease progresses. In this article, the author discusses advances in the field of frontotemporal dementia, including discoveries regarding the neuropathological and genetic causes of the disease, revisions in the diagnostic criteria for the clinical syndromes of behavioral variant frontotemporal dementia and primary progressive aphasia, current pharmacological and behavioral interventions, and emerging clinical trials.
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• Since 2011, revised diagnostic criteria have been published for the 3 clinical variants of frontotemporal dementia (FTD): behavioral variant frontotemporal dementia, nonfluent variant primary progressive aphasia, and semantic variant primary progressive aphasia.
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• Corticobasal syndrome, progressive supranuclear palsy, and motor neuron disease/amyotrophic lateral sclerosis are considered to exist within the frontotemporal dementia disease spectrum.
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• The most common frontotemporal dementia-causing genes and pathological proteins have been identified and are actively being pursued for potential disease-modifying therapies.
Historical note and terminology
Over 100 years ago in 1892, Arnold Pick described the first case of a progressive dementia syndrome that involved atrophy of the frontal and temporal lobes (31). However, it was not until 1911 that Alois Alzheimer first described the histopathology in these cases, which he termed “Pick bodies” (01). In the 1920s, Onari and Spatz went on to establish the clinical-pathological relationship, which was subsequently given the name “Pick’s disease” (30). Over time, interest in the disease dwindled as it became apparent that many clinical cases of Pick disease did not display the typical histological signature of Pick cells and Pick bodies on autopsy.
As neuroimaging techniques were developed and refined over the 1980s, frontotemporal atrophy was demonstrated with increasing frequency in vivo, and researchers once again began to take an interest in the disease. The first consensus document for diagnosis and classification of frontotemporal dementia was developed in 1994 through the collaboration of the Lund and Manchester groups (often referred to as the “Lund-Manchester” criteria for frontotemporal dementia) (06). These criteria were further refined in 1998, when Neary and colleagues published the “Consensus on Frontotemporal Lobar Degeneration,” which included diagnostic criteria for the 3 clinical variants of frontotemporal dementia (behavioral, progressive non-fluent aphasia, and semantic dementia) (26). These criteria laid the foundation for clinicians and researchers in the field and have greatly contributed to the proliferation of research on frontotemporal dementia in the past 15 years.
As alluded to above, the concept and nosology of frontotemporal dementia has undergone many revisions since it was first described. Pick disease (30), frontal lobe degeneration (05), dementia of the frontal lobe type (26), and frontotemporal dementia (06) have all been used to describe the disease. The term “Pick complex” has also been suggested to encompass all related clinical and pathological entities of frontotemporal dementia (18). At this time, frontotemporal dementia is used to signify the clinical manifestation of the disease, whereas frontotemporal lobar degeneration is used to describe the disease on pathological examination.