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Semantic Dementia

Summary

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  • Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive loss of semantic knowledge and language comprehension
  • It is a variant of frontotemporal lobar degeneration (FTLD) with predominant temporal lobe atrophy
  • Imaging shows characteristic asymmetric anterior temporal lobe atrophy, typically left-sided1

Pathophysiology

  • SD is associated with TDP-43 pathology in most cases
  • Characterised by progressive neuronal loss and gliosis in the anterior temporal lobes
  • Typically asymmetric, with the left side more severely affected
  • Involves the temporal pole, inferior and middle temporal gyri, and fusiform gyrus
  • Relative sparing of the superior temporal gyrus and hippocampus in early stages

Demographics

  • Typically presents in the 50s to 60s
  • No significant gender predilection
  • Rare familial cases reported, but most are sporadic
  • Estimated prevalence of 1-5 per 100,000 individuals

Diagnosis

  • Clinical presentation:
    • Progressive loss of word meaning and object knowledge
    • Fluent speech with semantic paraphasias
    • Surface dyslexia and dysgraphia
    • Preserved episodic memory and visuospatial skills
  • Neuropsychological testing:
    • Impaired semantic memory and naming
    • Preserved phonology, syntax, and working memory
    • Relatively intact episodic memory and visuospatial function
  • Genetic testing:
    • GRN and MAPT mutations in rare familial cases

Imaging

  • MRI findings:
    • Asymmetric anterior temporal lobe atrophy, typically left-sided
    • Progressive atrophy of the temporal pole, inferior and middle temporal gyri
    • Relative sparing of the superior temporal gyrus and hippocampus
    • Involvement of the fusiform gyrus and anterior insula
  • FDG-PET:
    • Hypometabolism in the affected anterior temporal lobe
    • May show more extensive involvement than structural MRI
  • SPECT:
    • Decreased perfusion in the anterior temporal lobe

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Treatment

  • No disease-modifying therapy. The hallmark is asymmetric (usually left) anterior temporal-pole "knife-edge" atrophy, part of the frontotemporal degeneration spectrum

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Alzheimer's Disease Symmetric hippocampal and entorhinal cortex atrophy without anterior-to-posterior gradient; posterior parietal and precuneus hypometabolism on FDG-PET
Frontotemporal dementia (behavioural variant) More symmetric frontal and anterior temporal atrophy; less pronounced asymmetric anterior temporal predominance
Primary Progressive Aphasia (logopenic variant) Left posterior temporal and inferior parietal atrophy rather than anterior temporal lobe predominance
Autoimmune limbic encephalitis Bilateral mesial temporal T2/FLAIR hyperintensity with swelling; may enhance; more acute onset than neurodegenerative atrophy

  1. Klimova et al. Semantic Dementia: A Mini-Review. 2018. Mini reviews in medicinal chemistry - Open in new tab. ↩