frontotemporal dementia

Last edited 09/2018 and last reviewed 08/2023

Frontotemporal dementia

• refers to a diverse group of conditions that collectively are a major cause of young onset dementia
  • is an umbrella clinical term that encompasses a group of neurodegenerative diseases characterised by progressive deficits in behaviour, executive function, or language
    • first description of a patient with frontotemporal dementia was made by Arnold Pick in 1892
• Alois Alzheimer recognised the characteristic association with Pick bodies and named the clinicopathological entity Pick's disease, which led to the use of Pick's disease as a synonym for frontotemporal dementia
  
  
• produces selective brain atrophy involving the frontal and temporal lobes, requiring brain magnetic resonance imaging for accurate diagnosis
  • use either: FDG-PET or perfusion SPECT.
    
    
• is a common type of dementia, particularly in patients younger than 65 years
  • substantially less common than Alzheimer's disease, with estimates of population prevalence ranging from four to 15 per 100 000 before age 65 years in European and US epidemiological studies (1)
    • although onset is typically in the sixth decade of life, it may begin as early as the third or as late as the ninth decade, and the prevalence of FTD in older age groups has almost certainly been underestimated (1)
      
      
• can mimic many psychiatric disorders because of the prominent behavioural features
  • present chiefly as progressive aphasia or as disintegration of personality and behaviour that may be misdiagnosed as a psychiatric disorder
    
    
• up to about 20% of cases arise from dominant mutations in one of three major causative genes (2)
  • an autosomal dominant inheritance pattern or identifiable disease-causing mutations in around 10-20% of cases across large published series
  • most familial cases of FTD have mutations in the microtubule associated protein tau (MAPT) or progranulin (GRN) genes or the hexanucleotide repeat expansion in the C9ORF72 gene
    
    
• commonly associated with other neurological impairment, in particular parkinsonism or motor neurone disease
  
  
• clinical features
  • three clinical variants:
    • behavioural-variant frontotemporal dementia, which is associated with early behavioural and executive deficits
    • non-fluent variant primary progressive aphasia, with progressive deficits in speech, grammar, and word output
    • semantic-variant primary progressive aphasia, which is a progressive disorder of semantic knowledge and naming
  • about 12.5% of patients with behavioural-variant frontotemporal dementia develop motor neuron disease, typically including upper motor neuron signs (hyper-reflexia, extensor plantar response, spasticity), lower motor neuron signs (weakness, muscle atrophy, fasciculations), dysarthria, dysphagia, and pseudobulbar affect (3)
    • mild features of motor neuron disease can occur in up to 40% of patients with frontotemporal dementia
      
      
• treatment remains supportive, but patients and families need extensive counselling, future planning, and involvement of social and mental health services
  • no approved disease-modifying drugs are available for the treatment of frontotemporal dementia (1,5)
  • focused on management of behavioural symptoms
    • severity of compulsion, agitation, aggressiveness, impulsivity, and aberrant eating behaviour can improve with the use of selective serotonin reuptake inhibitors (4)
    • behavioural abnormalities can be managed with low doses of atypical antipsychotics (4) - however caution should be used when treating elderly patients with dementia with atypical antipsychotics because of increased risk of mortality secondary to cardiac events, falls, and infections
    • cholinesterase inhibitors are not beneficial
    • memantine does not improve or delay progression of frontotemporal dementia symptoms

Reference:

• Warrend JD et al. Frontotemporal dementia. BMJ. 2013; 347: 827.
• Vieira RT, Caixeta L, Machado S, et al. Epidemiology of early-onset dementia: a review of the literature. Clin Pract Epidemiol Ment Health. 2013; 9:88-95.
• Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor neuron dysfunction in frontotemporal dementia. Brain. 2011; 134:2582-94.
• Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2013; 11:CD00662
• NICE (June 2018).Dementia