Frontotemporal dementia

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Frontotemporal dementia (FTD) includes a diverse range of pathologies that affect predominantly the frontal and temporal lobes. Diagnostic criteria exist[1].
LogoKeyPointsBox.pngFor possible bvFTD 3 out of[1]:
  • Early behavioural disinhibition
  • Early apathy or inertia
  • Early loss of sympathy or empathy
  • Early perseverative, stereotyped or compulsive/ritualistic behaviour
  • Hyperorality and dietary change
The clinical presentation is usually as either a progressive aphasia or as disintegration of personality and behaviour[2]. A major historical correlation was made by Arnold Pick, hence the term Pick's Disease which describes about 30% of the clinical cases. This is one of the tauopathies and characteristic Pick bodies are visible on microscopy. While as with dementia in general, close to a quarter have a strong genetic association, the associations are usually different to that of Alzheimer's disease[3] with the following genes involved mainly in RNA processing and post-transcriptional regulation of gene expression being important[4]:

Contents

Classification

Clinical

  1. Behavioural-variant frontotemporal dementia (bvFTD)
    • Early personality change, disinhibition and apathy
    • Loss of sympathy and empathy
    • Stereotyped behaviours
    • Binge eating or drinking (hyperorality)
    • Poor insight
    • Possibly decreased perception pain
    • About 12% develop motor neuron disease (rarer in other presentations)
    • About 40% develop parkinsonism
    • Early involvement of fronto-insular cortex, orbitofrontal cortex and anterior cingulate-frontal transition zone
  2. Primary progressive aphasia (PPA)
    • Presentation is of progressive dysphasia and other language dysfunction for first 2 years of dementia
      • Can occur in Alzheimer's but usually with visual features thus excluded if:
        1. Prominant early defects in episodic memory, visual memory or visuoperceptial skills
        2. Prominant early behavioural disturbances
  3. Semantic-variant primary progressive aphasia(sv-PPA)
    • Impaired confrontational naming and impaired single word comprehension
    • At least 3 of:
      1. Impaired object knowledge
      2. Surface dyslexia or dysgraphia
      3. Spared repetition
      4. Spared speech production
    • Semantic dysphasia and associative agnosia
    • 90% have frontotemporal lobar degeneration-TDP type C
  4. Non-fluent variant primary progressive aphasia (nfv-PPA)
    • At least one of:
      1. Agrammatism in production
        • Ommission or misuse of grammar
      2. Apraxia of speech
        • speech sound errors
    • At least two of:
      1. Impaired comprehension of complex sentences
      2. Spared single-word comprehension
        • mild anomia for verbs however possible
      3. Spared object knowledge
    • Often caused by frontotemporal lobar degeneration-TDP type A

Pathological

Most cases are associated with abnormal disposition of one of 3 proteins:

  1. Microtubule-associated protein tau (coded by MAPT) causing frontotemporal lobar degeneration-tau
  2. TAR DNA-binding protein 43 (TDP-43)
    • About 50% of cases. Subclassified as:
      1. Frontotemporal lobar degeneration-TDP type A
      2. Frontotemporal lobar degeneration-TDP type B
      3. Frontotemporal lobar degeneration-TDP type C
        • Causes almost all cases of sv-PPA
  3. RNA-binding protein FUS (coded by FUS) causing frontotemporal lobar degeneration-FUS
    • Up to 10% of cases
    • Early onset with severe disinhibition, psychiatric symptoms and no motor or language issues

Differential

The differential diagnosis is wide including most causes of dementia, since perhaps less than 5% of dementia is frontotemporal dementia.

References