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Updated: Aug 23, 2025

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Changing perspectives on frontotemporal dementia: A review.

Julie S Snowden1,2

  • 1Cerebral Function Unit, Manchester Centre for Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK.

Journal of Neuropsychology
|October 31, 2022
PubMed
Summary

Frontotemporal dementia (FTD) understanding has evolved, revealing diverse clinical presentations, underlying pathologies (tau, TDP-43, FUS), and genetic links. Recognizing this heterogeneity is key for diagnosis and treatment.

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Area of Science:

  • Neuroscience
  • Neurology
  • Genetics

Background:

  • Frontotemporal dementia (FTD) was initially viewed as a behavioral and executive disorder.
  • Current understanding recognizes FTD's association with language, conceptual knowledge, and praxis deficits.
  • FTD presents heterogeneously, including links with motor neurone disease (MND), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).

Purpose of the Study:

  • To examine the evolution of frontotemporal dementia (FTD) understanding over four decades.
  • To highlight the recognized heterogeneity in FTD's clinical, pathological, and genetic aspects.
  • To emphasize the importance of understanding FTD diversity for improved clinical outcomes.

Main Methods:

  • Review of literature and clinical observations over the past 40 years.
Keywords:
behavioural variant FTDclinicopathological relationshipsprogressive aphasiasemantic dementia

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  • Analysis of clinical phenotypes, pathological substrates (tau, TDP-43, FUS), and genetic mutations.
  • Correlation of specific clinical features with underlying pathologies and genetic factors.

    • Main Results:

    • FTD understanding has expanded beyond behavioral changes to include language and cognitive alterations.
    • Established associations exist between FTD and other neurodegenerative diseases like MND, PSP, and CBD.
    • Predictable relationships are identified between clinical presentation, pathology (tau, TDP-43, FUS), and genetic mutations (GRN, C9orf72).
    • FTD can present across a wide age range, not exclusively in early-onset cases.

    Conclusions:

    • Understanding the heterogeneity of frontotemporal dementia (FTD) is critical for accurate diagnosis and patient management.
    • Established links between clinical syndromes, specific proteinopathies, and genetic factors aid in subtyping FTD.
    • Further research is needed to resolve classification issues and develop targeted therapies for FTD subtypes.