Deconstructing the transdiagnostic nature of language symptoms in frontotemporal dementias

Primary progressive aphasia (PPA) is a group of neurodegenerative disorders featuring primary-language impairments and typically classified into three-variants: semantic, non-fluent and logopenic. Yet their language profiles significantly overlap. Language deficits can also occur in other frontotemporal dementias (FTD) like progressive supranuclear palsy and corticobasal syndrome, suggesting that language symptoms are transdiagnostic. Though brain atrophy determines language difficulties, similar atrophy profiles often are related to different language deficits, and different atrophies can cause similar impairments (e.g., logopenic/non-fluent PPA). We apply a transdiagnotic approach to link the language variantions across FTD-PPA spectrum to their underlying neuroanatomical factors. Principal component analysis identified three language dimensions (motor-speech/phonology, semantics and syntax) and thirteen atrophic dimensions, including temporal, frontal, parietal regions. While anterior temporal lobe atrophy predicts semantic impairments, frontoparietal atrophies predict motor-speech/phonology, and syntax. Atrophy and language variations across FTD-PPA syndromes are deconstructed on a brain-behaviour continuum, with only semantic variants being clearly separate.