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Frontotemporal Dementia (FTD)

Summary

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  • Progressive neurodegenerative disorder affecting frontal and temporal lobes
  • Characterised by behavioural changes, language deficits, and executive dysfunction
  • Imaging shows atrophy in frontal and/or temporal lobes, with functional changes on PET/SPECT

Pathophysiology

  • Abnormal accumulation of tau protein or TDP-43 in neurons
  • Three main subtypes:
    • Behavioural variant (bvFTD)
    • Semantic variant primary progressive aphasia (svPPA)
    • Nonfluent variant primary progressive aphasia (nfvPPA)
  • Associated with mutations in genes such as MAPT, GRN, and C9orf72

Demographics

  • Second most common cause of early-onset dementia after Alzheimer's disease
  • Typically affects individuals aged 45-65 years
  • Male to female ratio approximately 1:1
  • Prevalence estimated at 15-22 per 100,000 individuals

Diagnosis

  • Based on clinical presentation, neuropsychological testing, and neuroimaging
  • Core diagnostic features:
    • bvFTD: Behavioural disinhibition, apathy, loss of empathy, perseverative behaviours
    • svPPA: Loss of word meaning, impaired object recognition
    • nfvPPA: Agrammatism, apraxia of speech
  • Genetic testing for familial cases
  • Cerebrospinal fluid biomarkers (e.g., tau, TDP-43) may aid in diagnosis

Imaging

  • Structural MRI:
    • Atrophy in frontal and/or temporal lobes
    • bvFTD: Frontal, anterior temporal, and insular atrophy
    • svPPA: Asymmetric anterior temporal lobe atrophy (often left > right)
    • nfvPPA: Left inferior frontal and insular atrophy
  • Functional imaging (PET/SPECT):
    • Hypometabolism/hypoperfusion in affected regions
    • FDG-PET shows reduced glucose metabolism in frontal and temporal lobes
  • Advanced MRI techniques:
    • Diffusion tensor imaging (DTI) shows white matter tract degeneration
    • Resting-state fMRI reveals altered functional connectivity patterns

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  • 60-year-old patient presented with behavioural change and speech changes.
  • MRI showed left frontal and temporal atrophy; the superior frontal gyrus was knife-blade thin.
  • FDG-PET showed marked hypometabolism in the frontal and temporal lobes.
  • Amyloid PET was negative with preserved grey-white matter differentiation.

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  • 65-year-old patient presented after a significant deterioration in cogntive function, depression and various forms of socially inappropriate behaviour.
  • CT showed marked right anterior temporal atrophy and milder atrophy in the basal frontal lobes around the rectus gyri.

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  • A 60-year-old patient presented with disinhibition and impaired naming and verbal memory.
  • MRI showed pronounced anterior temporal, milder left parietal, and no frontal lobe atrophy. There was particularly pronounced atrophy of the amygdalae.
  • CSF amyloid markers were normal, making Alzheimer's disease unlikely. Genetic testing revealed a MAPT mutuation as the cause of frontotemporal dementia.

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  • A 60-year-old patient presented with disinbition and language disturbance.
  • MRI showed marked frontal and mild hippocampal atrophy with preservation of the amygdalae.
  • Genetic testing revealed a progranulin mutation.

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  • A 60-year-old patient presented with apathy and increased weight. The patient's partner reported episodes of reckless spending in the preceeding year. The patient had a strong family history for dementia.
  • MRI showed symmetrical frontal lobe atrophy. The frontal horns were larger than the trigones. The olfactory sulci were wided ("Crab sign").
  • Genetic testing revealed a C9ORF72 mutation as the cause of the frontotemporal dementia.

Treatment

  • No disease-modifying treatments currently available
  • Symptomatic management:
    • Selective serotonin reuptake inhibitors (SSRIs) for behavioural symptoms
    • Antipsychotics for severe behavioural disturbances (use with caution)
    • Speech and language therapy for language variants
  • Non-pharmacological interventions:
    • Cognitive rehabilitation
    • Caregiver education and support
  • Ongoing clinical trials for potential disease-modifying therapies:
    • Tau-targeted therapies
    • Antisense oligonucleotides for genetic forms
  • Multidisciplinary care approach involving neurologists, psychiatrists, and allied health professionals

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Alzheimer's Disease Prominent memory loss early in disease course; hippocampal atrophy on imaging
Vascular Dementia Stepwise decline; evidence of cerebrovascular disease on imaging
Normal Pressure Hydrocephalus Enlarged ventricles out of proportion to sulcal atrophy; tight high convexity sulci; no focal frontal or temporal atrophy