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More Than Words: Extra-Sylvian Neuroanatomic Networks Support Indirect Speech Act Comprehension and Discourse in Behavioral Variant Frontotemporal Dementia
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In: Front Hum Neurosci (2021)
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Digital Speech Analysis in Progressive Supranuclear Palsy and Corticobasal Syndromes
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In: J Alzheimers Dis (2021)
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Automated analysis of lexical features in Frontotemporal Degeneration
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In: Cortex (2021)
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Automated Analysis of Digitized Letter Fluency Data
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In: Front Psychol (2021)
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New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures.
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association, vol 16, iss 1 (2020)
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Utility of the global CDR® plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium.
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association, vol 16, iss 1 (2020)
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| 7 |
New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures.
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association, vol 16, iss 1 (2020)
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Utility of the global CDR® plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium.
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association, vol 16, iss 1 (2020)
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C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts.
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In: Neurology, vol 95, iss 24 (2020)
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| 10 |
C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts
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Utility of the global CDR® plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium
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In: Alzheimers Dement (2020)
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C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts
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Costa, Beatrice; Manzoni, Claudia; Bernal-Quiros, Manuel; Kia, Demis A.; Aguilar, Miquel; Alvarez, Ignacio; Alvarez, Victoria; Andreassen, Ole; Anfossi, Maria; Bagnoli, Silvia; Benussi, Luisa; Bernardi, Livia; Binetti, Giuliano; Blackburn, Daniel; Boada, Mercè; Borroni, Barbara; Bowns, Lucy; Bråthen, Geir; Bruni, Amalia C.; Chiang, Huei-Hsin; Clarimon, Jordi; Colville, Shuna; Conidi, Maria E.; Cope, Tom E.; Cruchaga, Carlos; Cupidi, Chiara; Di Battista, Maria Elena; Diehl-Schmid, Janine; Diez-Fairen, Monica; Dols-Icardo, Oriol; Durante, Elisabetta; Flisar, Dušan; Frangipane, Francesca; Galimberti, Daniela; Gallo, Maura; Gallucci, Maurizio; Ghidoni, Roberta; Graff, Caroline; Grafman, Jordan H.; Grossman, Murray; Hardy, John; Hernández, Isabel; Holloway, Guy J.T.; Huey, Edward D.; Illán-Gala, Ignacio; Karydas, Anna; Khoshnood, Behzad; Kramberger, Milica G.; Kristiansen, Mark; Lewis, Patrick A.; Lleó, Alberto; Madhan, Gaganjit K.; Maletta, Raffaele; Maver, Aleš; Menendez-Gonzalez, Manuel; Milan, Graziella; Miller, Bruce; Mol, Merel O.; Momeni, Parastoo; Moreno-Grau, Sonia; Morris, Chris M.; Nacmias, Benedetta; Nilsson, Christer; Novelli, Valeria; Öijerstedt, Linn; Padovani, Alessandro; Pal, Suvankar; Panchbhaya, Yasmin; Pastor, Pau; Peterlin, Borut; Piaceri, Irene; Pickering-Brown, Stuart; Pijnenburg, Yolande A.L.; Puca, Annibale A.; Rainero, Innocenzo; Rendina, Antonella; Richardson, Anna M.T.; Rogaeva, Ekaterina; Rogelj, Boris; Rollinson, Sara; Rossi, Giacomina; Rossmeier, Carola; Rowe, James B.; Rubino, Elisa; Ruiz, Agustín; Sanchez-Valle, Raquel; Sando, Sigrid B.; Santillo, Alexander F.; Saxon, Jennifer; Scarpini, Elio; Serpente, Maria; Smirne, Nicoletta; Sorbi, Sandro; Suh, EunRan; Tagliavini, Fabrizio; Thompson, Jennifer C.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Van der Zee, Julie; Van Broeckhoven, Christine; van Rooij, Jeroen; Van Swieten, John C.; Veronesi, Arianna; Vitale, Emilia; Waldö, Maria L.; Woodward, Cathy; Yokoyama, Jennifer; Escott-Price, Valentina; Polke, James M.; Ferrari, Raffaele
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In: Neurology (2020)
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Abstract:
OBJECTIVE: We sought to characterize C9orf72 expansions in relation to genetic ancestry and age at onset (AAO) and to use these measures to discriminate the behavioral from the language variant syndrome in a large pan-European cohort of frontotemporal lobar degeneration (FTLD) cases. METHODS: We evaluated expansions frequency in the entire cohort (n = 1,396; behavioral variant frontotemporal dementia [bvFTD] [n = 800], primary progressive aphasia [PPA] [n = 495], and FTLD–motor neuron disease [MND] [n = 101]). We then focused on the bvFTD and PPA cases and tested for association between expansion status, syndromes, genetic ancestry, and AAO applying statistical tests comprising Fisher exact tests, analysis of variance with Tukey post hoc tests, and logistic and nonlinear mixed-effects model regressions. RESULTS: We found C9orf72 pathogenic expansions in 4% of all cases (56/1,396). Expansion carriers differently distributed across syndromes: 12/101 FTLD-MND (11.9%), 40/800 bvFTD (5%), and 4/495 PPA (0.8%). While addressing population substructure through principal components analysis (PCA), we defined 2 patients groups with Central/Northern (n = 873) and Southern European (n = 523) ancestry. The proportion of expansion carriers was significantly higher in bvFTD compared to PPA (5% vs 0.8% [p = 2.17 × 10(−5); odds ratio (OR) 6.4; confidence interval (CI) 2.31–24.99]), as well as in individuals with Central/Northern European compared to Southern European ancestry (4.4% vs 1.8% [p = 1.1 × 10(−2); OR 2.5; CI 1.17–5.99]). Pathogenic expansions and Central/Northern European ancestry independently and inversely correlated with AAO. Our prediction model (based on expansions status, genetic ancestry, and AAO) predicted a diagnosis of bvFTD with 64% accuracy. CONCLUSIONS: Our results indicate correlation between pathogenic C9orf72 expansions, AAO, PCA-based Central/Northern European ancestry, and a diagnosis of bvFTD, implying complex genetic risk architectures differently underpinning the behavioral and language variant syndromes.
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Keyword:
Article
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URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836664/
https://doi.org/10.1212/WNL.0000000000010914
http://www.ncbi.nlm.nih.gov/pubmed/32943482
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| 13 |
Automated analysis of natural speech in amyotrophic lateral sclerosis spectrum disorders
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In: Neurology (2020)
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| 14 |
C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts
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| 15 |
Automated analysis of lexical features in Frontotemporal Degeneration
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In: medRxiv (2020)
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| 16 |
Clinical Correlates of Alzheimer's Disease Cerebrospinal Fluid Analytes in Primary Progressive Aphasia
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| 17 |
A Longitudinal Study of Speech Production in Primary Progressive Aphasia and Behavioral Variant Frontotemporal Dementia
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In: Brain Lang (2019)
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Longitudinal progression of grey matter atrophy in non-amnestic Alzheimer’s disease
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In: Brain (2019)
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| 19 |
Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia
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In: ISSN: 0364-5134 ; EISSN: 1531-8249 ; Annals of Neurology ; https://hal-univ-fcomte.archives-ouvertes.fr/hal-03630161 ; Annals of Neurology, Wiley, 2018, 84 (5), pp.729-740. ⟨10.1002/ana.25333⟩ (2018)
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| 20 |
Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia
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In: ISSN: 0364-5134 ; EISSN: 1531-8249 ; Annals of Neurology ; https://www.hal.inserm.fr/inserm-02749861 ; Annals of Neurology, Wiley, 2018, 84 (5), pp.729-740. ⟨10.1002/ana.25333⟩ (2018)
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