- Clinical science
Frontotemporal dementia (FTD) is a progressive neurodegenerative disease of the frontal and/or temporal lobe generally caused by mutations to proteins in the brain (e.g., Tau, progranulin). Pick's disease, formerly used synonymously with FTD, is actually a specific subtype of FTD that can only be diagnosed pathologically; therefore, the two terms are not synonymous. Onset usually occurs in middle-aged individuals (40–60 years). Early symptoms are characterized by inappropriate social behavior (e.g., disinhibition, apathy), but patients typically continue to exhibit normal intelligence and orientation. As the disease progresses, patients may develop motor deficits and akinetic parkinsonism as an end‑stage syndrome. Diagnosis of FTD is based on a combination of factors, including the clinical criteria of dementia and possible frontotemporal brain atrophy on CT or MRI. Further diagnostic procedures may be considered to rule out other possible causes of dementia. No effective causal treatment for FTD exists and symptomatic treatment is limited to associated symptoms (e.g., depression). The disease usually has a fatal outcome within six years.
- FTD is a heterogeneous group of syndromes that involve degeneration of the frontal, insular, and/or temporal cortices; and manifest with a number of symptoms of dementia. FTD is sometimes still referred to as Pick's disease, but this term should be avoided.
- FTD syndromes are often considered special types of Alzheimer's disease (however, initial symptoms are typically not memory‑related).
- Generally associated with pathological intracellular inclusion bodies; (Pick bodies) that are caused by mutations in tau or progranulin proteins
- Also associated with ubiquitin inclusion bodies hypothesized to be caused by dysfunction of the ubiquitin proteasome system
- Familial predisposition (autosomal dominant): ∼ 10–25% of FTD cases
- Various genes have been associated with inherited forms of FTD (particularly C9ORF72, MAPT, and GRN).
General features of FTD
Early changes in personality and behavior → failure to observe social etiquette
- Disinhibition (e.g., hypersexual behavior)
- Exaggerated emotional display
- Binge eating (particularly of sweet foods)
- Changes in cognitive functioning
- Parkinsonism (in later stages)
- Pyramidal signs (e.g., tendon hyperreflexia, )
Characteristic features of each FTD syndrome
- bvFTD → early changes in personality, apathy
- PNFA → language impairment (e.g., grammatical errors, apraxia)
- SD → language impairment (specifically comprehension)
- PCA → visual disorders (e.g., blurred vision)
- CBS → asymmetric kinetic movement disorder
Patients with FTD display changes to personality and social behavior, but their memory generally remains intact!
The diagnosis of FTD syndromes is based on a combination of factors:
- Clinical diagnosis of a dementia syndrome → see
- Other tests to rule out or confirm specific abnormalities
Pathological changes in FTD are commonly referred to as frontotemporal lobar degeneration (FTLD).
- Atrophy of the temporal and/or frontal lobes
- Often beginning on one side and subsequently affecting both hemispheres
- Nonspecific gliosis ; formation of microvacuoles and loss of neuronal tissue
- Swollen neurons (= pick cells)
Detection of different types of intracellular inclusions in surviving neurons (tau or TDP-43 in approx. 90% of cases)
Pick bodies; (= FTLD-tau) .: cytoplasmic inclusions of aggregated tau proteins
- Associated with Pick's disease
- Found in ∼ 40% of patients with FTLD
- Also found in other neurodegenerative diseases, e.g. progressive supranuclear palsy, corticobasal degeneration, amyotrophic lateral sclerosis (ALS) ̶ Parkinson dementia disease complex of Guam
- Silver stain: classic Pick bodies stain positive, but many patients with tau inclusions stain negative
- FTLD‑TDP: inclusions with hyperphosphorylated TDP‑43 (a protein involved in gene transcription)
- Pick bodies; (= FTLD-tau) .: cytoplasmic inclusions of aggregated tau proteins
The differential diagnoses listed here are not exhaustive.
No curative treatment exists → symptomatic treatment
- Supportive therapy (e.g., behavioral therapy, speech therapy)
- Dietary measures