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Semantic dementia pathology — MRCPsych Paper A MCQ

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HardNeuropathologySemantic dementia pathologyMRCPsych Paper A

A 62-year-old man develops a 3-year progressive loss of single-word comprehension and knowledge about familiar objects. His speech remains fluent and grammatically correct, with preserved repetition and motor speech, but is increasingly empty of meaning. MRI shows marked left-greater-than-right anterior temporal lobe atrophy. Which neuropathological finding is most likely?

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Correct answer: B — FTLD-TDP type C with long TDP-43-positive dystrophic neurites

The clinical syndrome is semantic variant primary progressive aphasia, traditionally termed semantic dementia: progressive degradation of word and object meaning with fluent, grammatically preserved but empty speech and asymmetric anterior temporal atrophy. Its strongest clinicopathological association is FTLD-TDP type C, characterised by long TDP-43-positive dystrophic neurites, especially in superficial cortical layers. Pick-type FTLD-tau is more often associated with behavioural-variant frontotemporal dementia. Alzheimer pathology may underlie logopenic aphasia but is less consistent with preserved repetition and the focal anterior temporal pattern. FTLD-TDP type A is more strongly associated with progranulin-related disease and broader frontoparietal syndromes. FTLD-FUS usually presents with very early-onset behavioural disease rather than the characteristic semantic syndrome.

Reference: Borghesani V et al. Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology. NeuroImage: Clinical. 2020;28:102369. https://pubmed.ncbi.nlm.nih.gov/32798912/