Primary Progressive Aphasia Associated With GRN Mutations: New Insights Into the Nonamyloid Logopenic Variant.
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Saracino Dario, Ferrieux Sophie, Noguès-Lassiaille Marie, Houot Marion, Funkiewiez Aurélie, Sellami Leila, Deramecourt Vincent, Pasquier Florence, Couratier Philippe, Pariente Jérémie, Géraudie Amandine, Epelbaum Stéphane, Wallon David, Hannequin Didier, Martinaud Olivier, Clot Fabienne, Camuzat Agnès, Bottani Simona, Rinaldi Daisy, Auriacombe Sophie, Sarazin Marie, Didic Mira, Boutoleau-Bretonnière Claire, Thauvin-Robinet Christel, Lagarde Julien, Roué-Jagot Carole, Sellal François, Gabelle Audrey, Etcharry-Bouyx Frédérique, Morin Alexandre, Coppola Cinzia, Levy Richard, Dubois Bruno, Brice Alexis, Colliot Olivier, Gorno-Tempini Maria Luisa, Teichmann Marc, Migliaccio Raffaella, Le Ber Isabelle, French Research Network on FTD/FTD-ALS
Аннотация
METHODS: Patients with PPA carrying GRN mutations (PPA-GRN) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and gray matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls and patients with sporadic PPA.
RESULTS: Among the 235 patients with PPA, 45 (19%) carried GRN mutations, and we studied 32 of these. We showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (n = 13, 41%), followed by nonfluent/agrammatic (nfvPPA; n = 9, 28%) and mixed forms (n = 8, 25%). Semantic variant was rather rare (n = 2, 6%). Patients with lvPPA, qualified as nonamyloid lvPPA, presented canonical logopenic deficit. Seven of 13 had a pure form; 6 showed subtle additional linguistic deficits not fitting criteria for mixed PPA and hence were labeled as logopenic-spectrum variant. GM atrophy involved primarily left posterior temporal gyrus, mirroring neuroanatomic changes of amyloid-positive-lvPPA. Patients with nfvPPA presented agrammatism (89%) rather than apraxia of speech (11%).
CONCLUSIONS: This study shows that the most frequent PPA variant associated with GRN mutations is nonamyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that the language network may be affected at different levels. GRN testing is indicated for patients with PPA, whether familial or sporadic. This finding is important for upcoming GRN gene-specific therapies.