Frontotemporal dementia

Pathogenesis

Frontotemporal dementia refers to a group of dementias characterised pathologically by degeneration of the frontal and temporal lobes at post-mortem. They are clinically and pathologically diverse. The most common histological findings at autopsy are intracellular inclusions of either hyperphosphorylated tau protein or TDP43.

Genetics 

  • Up to 25% of cases are inherited
  • Inheritance: AD
  • Genes:
    • MAPT
    • Progranulin
    • c9ORF72

Epidemiology

  • Age of onset: <65
  • Prevalence: 15 / 100,000 in 45 – 64 year olds

Presentation

Early FTD usually presents with an isolated cognitive deficit.

Behavioural variant:  presents with progressive behavioural change. Key features include:

  • Disinhibition
  • Apathy
  • Hyperorality
  • Compulsive behaviour

Primary progressive aphasia: presents with progressive aphasia with relative sparing of other cognitive domains. There are 3 subtypes:

  • Nonfluent: speech is stuttering, comprehension relatively spared
  • Semantic: impaired comprehension of concepts and naming
  • Logopaenic: impaired word-finding, slow speech

Motor features

  • There is a significant overlap between behavioural-variant FTD and ALS. Many patients develop an ALS-like clinical syndrome.

Investigation

The aim of investigations is to exclude reversible causes for dementia.

Tests

  • Bloods: FBC, U&E, LFT, HIV, B12, TFTs, Calcium
  • MRI: to exclude a structural frontal lesion

Definitive diagnosis, as with all dementias, is based on post-mortem biopsy findings.

Management

  • No effective disease-modifying therapy is available
  • Treatment is symptomatic and supportive