Frontotemporal Dementia (FTD)

Diseases, ,

Synonyms:

a.k.a. Frontotemporal lobar dementia FTLD

Diagnosis:

Clinical features, plus supportive imaging

Clinical features:

Behavioural symptoms:

  • Progressive change in personality
  • Decline of reasoning
  • Social inappropriateness

Primary progressive aphasia:

  • Anomia (inability to retrieve nouns upon demand),
  • Agrammatism (inappropriate word order or use of prepositions),
  • Loss of semantic knowledge about words and objects

Clinical variants: progressive nonfluent aphasia, semantic dementia,

Findings on Investigations:

CT: symmetric lobar atrophy of the temporal +/-frontal lobes
MRI: symmetric lobar atrophy of the temporal +/-frontal lobes
SPECT:

  • Regional hypoperfusion in frontal & anterior temporal lobes

Pathology:

Brain biopsy or autopsy findings: gold standard
See under the following headings
Tauopathies:

  • Tau accumulates (microtubule associated protein tau MAPT gene chr. 17q21)

Pick disease:

  • Pick bodies = tau positive intraneuronal inclusions in frontotemporal cortex & hippocampus.
  • Pick cells = tau positive neurons with swollen eosinophilic cytoplasm.
  • Cortical Neuronal loss & microvacuolation may occur

Multiple system tauopathy FTLD-MST:

  • Also affects substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus
  • Tau positive intraneuronal & glial inclusions
  • Usually familial

Frontotemporal dementia and parkinsonism linked to chromosome 17 FTLDP-17:

  • A rare familial form

Tau negative FTLD
FTLD with ubiquitin only staining FTLD-U:

  • The ubiquinated protein in the inclusions is TAR DNA binding protein 43 a.k.a. TDP-43 (TARDBP gene chr. 1). Normal neurons have TDP-43 in the nucleus, abnormal neurons have cytoplasmic TDP-43 inclusions.

FTLD with motor neuron disease FTLD-MND:

  • Cortical Microvacuolation & neuronal loss.
  • Subcortical gliosis. Basal ganglia atrophy.
  • Ubiquitin +TDP-43 inclusions in cortical neurons & hippocampal dentate granule cells
  • Degeneration of motor neurons
  • Dementia lacking distinctive histology DLDH

Neuronal intermediate filament inclusion disease (NIFID):

  • Neurofilament positive & alpha-internexin positive cytoplasmic inclusions, ubiquitin positive intranuclear inclusions

Genetic/familial forms in FTD:

  • Mutations in PGRN gene chr. 17q21, the protein is progranulin, causes FTLD-U.
  • Mutations in MAPT gene chr. 17q21, the protein is tau, causes: FTDP-17 or FTLD-MST
Pick’s disease:

Diagnosis, Pick’s disease:

  • CT or MRI: symmetric lobar atrophy of the temporal +/-frontal lobes

Pathology:

  • Autopsy findings are the gold standard
  • This is a form of frontotemporal dementia FTD

Treatment for Frontotemporal dementia:

Supportive care

Related articles: