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Primary Progressive Aphasia Associated With GRN Mutations: New Insights Into the Non-amyloid Logopenic Variant
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Saracino, Dario; Ferrieux, Sophie; NOGUES-LASSIAILLE, Marie; Houot, Marion; FUNKIEWIEZ, Aurelie; Sellami, Leila; Deramecourt, Vincent; Pasquier, Florence; Couratier, Philippe; PARIENTE, Jeremie; GERAUDIE, Amandine; Epelbaum, Stephane; Wallon, David; Hannequin, Didier; Martinaud, Olivier; Clot, Fabienne; CAMUZAT, Agnes; Bottani, Simona; Rinaldi, Daisy; Auriacombe, Sophie; Sarazin, Marie; Didic, Mira; Boutoleau-Bretonnière, Claire; Thauvin-Robinet, Christel; Lagarde, Julien; ROUE-JAGOT, Carole; SELLAL, Francois; Gabelle, Audrey; ETCHARRY-BOUYX, Frederique; 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
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In: ISSN: 0028-3878 ; EISSN: 1526-632X ; Neurology ; https://hal.archives-ouvertes.fr/hal-03281660 ; Neurology, American Academy of Neurology, 2021, ⟨10.1212/wnl.0000000000012174⟩ (2021)
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Abstract:
International audience ; OBJECTIVE: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with progranulin (GRN) mutations, and study their neuroanatomical correlates. METHODS: PPA patients carrying GRN mutations (PPA-GRN) were selected amongst a national prospective research cohort of 1,696 frontotemporal dementia (FTD) patients, including 235 patients with PPA. All PPA patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and grey matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls, and sporadic PPA patients. RESULTS: Among the overall population of 235 patients, 45 (19%) carried GRN mutations. We studied 32 of these and showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (13, 41%), followed by non-fluent/agrammatic (nfvPPA: 9, 28%) and mixed forms (8, 25%). Semantic variant was rather rare (2, 6%). LvPPA patients, qualified as non-amyloid-lvPPA, presented canonical logopenic deficit. Seven out of 13 had a pure form, six showed subtle additional linguistic deficits not fitting criteria for mixed PPA, hence labelled as "logopenic-spectrum variant". GM atrophy primarily involved left posterior temporal gyrus, mirroring neuroanatomical changes of amyloid-positive-lvPPA. NfvPPA patients presented agrammatism (89%) rather than apraxia of speech (11%). CONCLUSIONS: This study shows that most frequent PPA variant associated with GRN mutations is non-amyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that language network may be affected at different levels. GRN testing is indicated for PPA patients, whether familial or sporadic. This finding is important for upcoming GRN gene-specific therapies.
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Keyword:
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie; Dementia aphasia; Frontotemporal dementia
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URL: https://hal.archives-ouvertes.fr/hal-03281660/document
https://hal.archives-ouvertes.fr/hal-03281660/file/NEUROLOGY-2020-153064v3-LeBer.pdf
https://hal.archives-ouvertes.fr/hal-03281660
https://doi.org/10.1212/wnl.0000000000012174
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Language Network Connectivity Increases in Early Alzheimer’s Disease
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In: J Alzheimers Dis (2021)
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Structural, Microstructural, and Metabolic Alterations in Primary Progressive Aphasia Variants
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In: ISSN: 1664-2295 ; Frontiers in Neurology ; https://hal.inria.fr/hal-01897015 ; Frontiers in Neurology, Frontiers, 2018, 9, ⟨10.3389/fneur.2018.00766⟩ (2018)
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Structural, microstructural and metabolic alterations in Primary Progressive Aphasia variants
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In: Annual meeting of the Organization for Human Brain Mapping - OHBM 2018 ; https://hal.inria.fr/hal-01764289 ; Annual meeting of the Organization for Human Brain Mapping - OHBM 2018, Jun 2018, Singapore, Singapore (2018)
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Inter-individual variability in discourse informativeness in elderly populations
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Structural, Microstructural, and Metabolic Alterations in Primary Progressive Aphasia Variants
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Inter-individual variability in discourse informativeness in elderly populations ...
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Inter-individual variability in discourse informativeness in elderly populations ...
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Pauses During Autobiographical Discourse Reflect Episodic Memory Processes in Early Alzheimer’s Disease
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