Progranulin-associated primary progressive aphasia: A distinct phenotype?

The neuropsychological features of the primary progressive aphasia (PPA) syndromes continue to be defined. Here we describe a detailed neuropsychological case study of a patient with a mutation in the progranulin (GRN) gene who presented with progressive word-finding difficulty. Key neuropsychological features in this case included gravely impoverished propositional speech with anomia and prolonged word-finding pauses, impaired speech repetition most marked for sentences, and severely impaired verbal (with preserved spatial) short-term memory. There was a dissociated profile of performance on semantic processing tasks: visual semantic processing was intact, while within the verbal domain, verb comprehension was impaired and processing of nouns was intact on tasks requiring direct semantic processing but impaired on tasks requiring associative or inferential processing. Brain MRI showed asymmetric left cerebral atrophy particularly affecting the temporo-parietal junction, supero-lateral temporal and inferior frontal lobes. This case most closely resembles the PPA syndrome known as the logopenic/phonological aphasia variant (LPA) however there were also deficits of grammar and speech repetition suggesting an overlap with the progressive non-fluent aphasia (agrammatic) variant (PNFA). Certain prominent features of this case (in particular, the profile of semantic impairment) have not been emphasised in previous descriptions of LPA or PNFA, suggesting that GRN may cause an overlapping PPA syndrome but with a distinctive cognitive profile. This neuropsychological evidence suggests that GRN-PPA may result from damage involving the temporo-parietal junction and its functional connections in both the dorsal and ventral language networks, with implications for our understanding of language network pathophysiology.