Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia

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Abstract
Importance Grammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable. Objective To develop a measure of grammatical comprehension and examine this comparatively in PPA variants and behavioural-variant frontotemporal degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in white matter tracts. Design Case–control study. Setting Academic medical centre. Participants 39 patients with variants of PPA (naPPA=12, lvPPA=15 and svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls. Main outcome measure Grammatical comprehension accuracy. Results Patients with naPPA had selective difficulty understanding cleft sentence structures, while all PPA variants and patients with bvFTD were impaired with sentences containing a centre-embedded subordinate clause. Patients with bvFTD were also impaired understanding sentences involving short-term memory. Linear regressions related grammatical comprehension difficulty in naPPA to left anterior-superior temporal atrophy and reduced FA in corpus callosum and inferior frontal-occipital fasciculus. Difficulty with centre-embedded sentences in other PPA variants was related to other brain regions. Conclusions and relevance These findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.

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