see also:

• dementia

• the 2nd most common cause of dementia in those under 65yrs age, and the 4th most common cause in those over 65 yrs of age (when vascular and Lewy Body dementia become more common)
• characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes

• prevalence 9-22 per 100,000 persons
• 1.6 to 2.3 new cases per 100,000 person-years
• peak age of onset between the ages of 50 and 65

• most are sporadic with no known genetic cause
• ~40% are genetic
  • mutations in the Tau gene (MAPT gene)
    • over 40 mutations known and can cause FTLD-tau
    • frontotemporal dementia and parkinsonism linked to q arm of chromosome 17 (FTDP-17)
      • MAPT mutations account for up to 50% of FTDP-17 cases
      • very rare (100 families worldwide) an autosomal dominant with incomplete penetrance
      • behavioral and personality changes
        • may include disinhibition, apathy, poor judgment, compulsive behavior, hyperreligiosity, alcoholism, illicit drug addiction, verbal and physical aggression, and abusive behaviors
      • cognitive impairment
        • progressive speech difficulties with non-fluent aphasia and executive function disorders
        • later echolalia, palilalia, verbal and vocal perseverations develop and eventually, mutism and progressive dementia set in
      • FTDP-17 Parkinsonism motor symptoms but with lack of resting tremor and poor or no response to levodopa therapy
  • mutations in the progranulin gene (PGRN)
    • can cause FTLD-TDP43
  • mutations in the CHMP2B gene
    • associated with a rare behavioural syndrome with ubiquitin positive pathology
  • hypermorphic mutations in the VCP gene
    • cause a TDP-43-positive FTLD which is associated with multisystem proteinopathy (MSP) which includes Paget's disease and inclusion body myopathy
  • hypomorphic mutation in the VCP gene
    • cause a unique type of FTLD-tau called vacuolar tauopathy with neurofibrillary tangles and neuronal vacuoles
  • mutations in the TDP-43 gene (known as TARBP or TAR DNA-binding protein)
    • very rare cause of FTLD, more commonly cause ALS
    • may be linked to C9ORF72 gene

• most have tau or ubiquitin inclusions on histology

• Pick bodies - tau positive inclusion bodies
• 45% of cases
• subtypes:
  • Pick's disease
  • corticobasal degeneration
  • progressive supranuclear palsy

• ubiquitin and TDP-43 positive, tau negative, FUS negative inclusion bodies
• ~50% of cases
• 5 subtypes:
  • Type A
  • Type B
    • often associated with ALS and C9ORF72 mutations
  • Type C
    • often associated with semantic dementia
  • Type D
    • associated with VCP mutations
  • Type E
    • has been associated with behavioral variant of frontotemporal dementia with a rapid clinical course

• rare genetic/pathological subtype
• single-digit percentage of cases

• 3 main clinical subtypes characterized by impairments in specific neural networks:
  • behavioural-variant frontotemporal dementia (bvFTD) accounts for 36-50% of cases
    • impaired social cognition
    • apathy or disinhibition
    • complex planning problems
    • frontal reflexes such as palmomental reflex sign
    • affects a frontomedian network
  • semantic dementia
    • fluent aphasia, anomia, impaired comprehension of word meaning, and visual associative agnosia (inability to match semantically-related pictures or objects)
    • mainly related to the inferior temporal poles and amygdalae
    • presumably the type affecting actor Bruce Willis
  • progressive nonfluent aphasia
    • progressive difficulties with speech production - hesitant, effortful speech, return of childhood stutter
    • affects the entire left frontotemporal network for phonological and syntactical processing

• varies with clinical subtype
• median survival times ranging from less than 3 years to over 12 years from the onset of symptoms
• generally progresses more rapidly than Alzheimer's dementia (AD)

• cognitive testing
• MRI
• [18F]fluorodeoxyglucose positron emission tomography (FDG-PET)

• ALS can present with frontotemporal dementia
  • FTD with Motor Neuron Disease (FTD-MND/ALS)
• see also dementia

• nil known

• no current Rx