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Progranulin-associated primary progressive aphasia: a distinct phenotype?
Jonathan D Rohrer1, Sebastian J Crutch, Elizabeth K Warrington
1Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, UK. rohrer@dementia.ion.ucl.ac.uk
Neuropsychologia
|September 22, 2009
Summary
A progranulin (GRN) gene mutation caused a unique primary progressive aphasia (PPA) overlapping logopenic/phonological and non-fluent aphasia variants, presenting distinct semantic deficits and word-finding difficulties.
Area of Science:
- Neuroscience
- Genetics
- Linguistics
Background:
- Primary progressive aphasia (PPA) syndromes are defined by progressive language impairment.
- Progranulin (GRN) gene mutations are a known cause of frontotemporal dementia, often presenting with PPA.
- Understanding the specific neuropsychological profiles associated with genetic PPA subtypes is crucial for diagnosis and management.
Observation:
- A case study of a patient with a GRN gene mutation revealed progressive word-finding difficulty.
- Key features included impoverished propositional speech, anomia, impaired sentence repetition, and poor verbal short-term memory.
- Semantic processing showed a dissociation: intact visual semantics, impaired verbal verb comprehension, and noun processing deficits in associative/inferential tasks.
Findings:
- The patient's presentation resembled logopenic/phonological aphasia (LPA) but also showed features of progressive non-fluent aphasia (PNFA), suggesting an overlapping syndrome.
- Distinctive semantic impairments, particularly in verbal associative and inferential processing, were noted.
- Brain MRI revealed left cerebral atrophy affecting temporo-parietal, temporal, and frontal lobes.
Implications:
- GRN mutations may lead to an overlapping PPA syndrome with a unique cognitive profile, distinct from classic LPA and PNFA.
- The findings suggest GRN-PPA involves damage to the temporo-parietal junction and its connections within dorsal and ventral language networks.
- This case deepens our understanding of language network pathophysiology in PPA and highlights the importance of genetic factors in PPA subtypes.
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