Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia

Kiran Samra; Amy M Macdougall; Arabella Bouzigues; Martina Bocchetta; David M Cash; Caroline V Greaves; Rhian S Convery; Chris Hardy; John C van Swieten; Harro Seelaar; Lize C Jiskoot; Fermin Moreno; Raquel Sanchez-Valle; Robert Laforce; Caroline Graff; Mario Masellis; Maria Carmela Tartaglia; James B Rowe; Barbara Borroni; Elizabeth Finger; Matthis Synofzik; Daniela Galimberti; Rik Vandenberghe; Alexandre de Mendonça; Chris R Butler; Alexander Gerhard; Simon Ducharme; Isabelle Le Ber; Isabel Santana; Florence Pasquier; Johannes Levin; Markus Otto; Sandro Sorbi; Jason D Warren; Jonathan D Rohrer; Lucy L Russell; Sónia Afonso; Maria Rosario Almeida; Sarah Anderl-Straub; Christin Andersson; Anna Antonell; Silvana Archetti; Andrea Arighi; Mircea Balasa; Myriam Barandiaran; Nuria Bargalló; Robart Bartha; Benjamin Bender; Alberto Benussi; Maxime Bertoux; Anne Bertrand; Valentina Bessi; Sandra Black; Sergi Borrego-Ecija; Jose Bras; Alexis Brice; Rose Bruffaerts; Agnès Camuzat; Marta Cañada; Valentina Cantoni; Paola Caroppo; Miguel Castelo-Branco; Olivier Colliot; Thomas Cope; Vincent Deramecourt; María De Arriba; Giuseppe Di Fede; Alina Díez; Diana Duro; Chiara Fenoglio; Camilla Ferrari; Catarina B Ferreira; Nick Fox; Morris Freedman; Giorgio Fumagalli; Aurélie Funkiewiez; Institut Du Cerveau; Alazne Gabilondo; Roberto Gasparotti; Serge Gauthier; Stefano Gazzina; Giorgio Giaccone; Ana Gorostidi; Rita Guerreiro; Carolin Heller; Tobias Hoegen; Begoña Indakoetxea; Vesna Jelic; Hans-Otto Karnath; Ron Keren; Gregory Kuchcinski; Tobias Langheinrich; Thibaud Lebouvier; Maria João Leitão; Albert Lladó; Gemma Lombardi; Sandra Loosli; Carolina Maruta; Simon Mead; Lieke Meeter; Gabriel Miltenberger; Rick Van Minkelen; Sara Mitchell; Katrina Moore; Benedetta Nacmias; Annabel Nelson; Linn Öijerstedt; Jaume Olives; Sebastien Ourselin; Alessandro Padovani; Jessica Panman; Janne M Papma; Yolande Pijnenburg; Cristina Polito; Enrico Premi; Sara Prioni; Catharina Prix; Rosa Rademakers; Veronica Redaelli; Daisy Rinaldi; Tim Rittman; Ekaterina Rogaeva; Adeline Rollin; Pedro Rosa-Neto; Giacomina Rossi; Martin Rossor; Beatriz Santiago; Dario Saracino; Sabrina Sayah; Elio Scarpini; Sonja Schönecker; Elisa Semler; Rachelle Shafei; Christen Shoesmith; Imogen Swift; Miguel Tábuas-Pereira; Mikel Tainta; Ricardo Taipa; David Tang-Wai; David L Thomas; Paul Thompson; Hakan Thonberg; Carolyn Timberlake; Pietro Tiraboschi; Emily Todd; Philip Van Damme; Mathieu Vandenbulcke; Michele Veldsman; Ana Verdelho; Jorge Villanua; Carlo Wilke; Ione Woollacott; Elisabeth Wlasich; Henrik Zetterberg; Miren Zulaica

doi:10.1093/braincomms/fcad036

Journal Articles Brain Communications Year : 2023

Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia

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Kiran Samra

Function : Author

Amy M Macdougall

Function : Author

Arabella Bouzigues

Function : Author

Martina Bocchetta

Function : Author
PersonId : 1363148
ORCID : 0000-0003-1814-5024

David M Cash

Function : Author
PersonId : 1364325
ORCID : 0000-0001-7833-616X

Caroline V Greaves

Function : Author

Rhian S Convery

Function : Author

Chris Hardy

Function : Author

John C van Swieten

Function : Author

Harro Seelaar

Function : Author
PersonId : 1343222
ORCID : 0000-0003-1989-7527

Lize C Jiskoot

Function : Author
PersonId : 1365754
ORCID : 0000-0002-1120-1858

Fermin Moreno

Function : Author

Raquel Sanchez-Valle

Function : Author
PersonId : 1336817
ORCID : 0000-0001-7750-896X

Robert Laforce

Function : Author

Caroline Graff

Function : Author
PersonId : 1343225
ORCID : 0000-0002-9949-2951

Karolinska Institutet [Stockholm]

Mario Masellis

Function : Author

Maria Carmela Tartaglia

Function : Author

James B Rowe

Function : Author

Barbara Borroni

Function : Author
PersonId : 1336812
ORCID : 0000-0001-9340-9814

Elizabeth Finger

Function : Author

Matthis Synofzik

Function : Author
PersonId : 1183781
ORCID : 0000-0002-2280-7273

Daniela Galimberti

Function : Author

Rik Vandenberghe

Function : Author
PersonId : 1343227
ORCID : 0000-0001-6237-2502

Alexandre de Mendonça

Function : Author

Chris R Butler

Function : Author

Alexander Gerhard

Function : Author
PersonId : 1365755
ORCID : 0000-0002-8071-6062

Simon Ducharme

Function : Author
PersonId : 1336818
ORCID : 0000-0002-7309-1113

Isabelle Le Ber

Function : Author

Institut du Cerveau = Paris Brain Institute

Isabel Santana

Function : Author

Florence Pasquier

Function : Author
PersonId : 1163029
ORCID : 0000-0001-9880-9788
IdRef : 03434991X

Institut de Pathologie [CHU Lille]

Johannes Levin

Function : Author

Markus Otto

Function : Author

Sandro Sorbi

Function : Author

Jason D Warren

Function : Author

Jonathan D Rohrer

Function : Author

Lucy L Russell

Function : Author
PersonId : 1364153

Sónia Afonso

Function : Author

Maria Rosario Almeida

Function : Author

Sarah Anderl-Straub

Function : Author

Christin Andersson

Function : Author

Anna Antonell

Function : Author

Silvana Archetti

Function : Author

Andrea Arighi

Function : Author

Mircea Balasa

Function : Author

Myriam Barandiaran

Function : Author

Nuria Bargalló

Function : Author

Robart Bartha

Function : Author

Benjamin Bender

Function : Author

Alberto Benussi

Function : Author

Maxime Bertoux

Function : Author

Anne Bertrand

Function : Author

Institut du Cerveau = Paris Brain Institute

Valentina Bessi

Function : Author

Sandra Black

Function : Author

Sergi Borrego-Ecija

Function : Author

Jose Bras

Function : Author

Alexis Brice

Function : Author
PersonId : 1104774
ORCID : 0000-0002-0941-3990
IdRef : 050512935

Institut du Cerveau = Paris Brain Institute

Rose Bruffaerts

Function : Author

Agnès Camuzat

Function : Author

Institut du Cerveau = Paris Brain Institute

Marta Cañada

Function : Author

Valentina Cantoni

Function : Author

Paola Caroppo

Function : Author

Miguel Castelo-Branco

Function : Author

Olivier Colliot

Function : Author

Institut du Cerveau = Paris Brain Institute

Thomas Cope

Function : Author

Vincent Deramecourt

Function : Author

Excellence Laboratory LabEx DISTALZ

María De Arriba

Function : Author

Giuseppe Di Fede

Function : Author

Alina Díez

Function : Author

Diana Duro

Function : Author

Chiara Fenoglio

Function : Author

Camilla Ferrari

Function : Author

Catarina B Ferreira

Function : Author

Nick Fox

Function : Author

Morris Freedman

Function : Author

Giorgio Fumagalli

Function : Author

Aurélie Funkiewiez

Function : Author

Institut du Cerveau = Paris Brain Institute

Institut Du Cerveau

Function : Author

Institut du Cerveau = Paris Brain Institute

Alazne Gabilondo

Function : Author

Roberto Gasparotti

Function : Author

Serge Gauthier

Function : Author

Stefano Gazzina

Function : Author

Giorgio Giaccone

Function : Author

Ana Gorostidi

Function : Author

Rita Guerreiro

Function : Author

Carolin Heller

Function : Author

Tobias Hoegen

Function : Author

Begoña Indakoetxea

Function : Author

Vesna Jelic

Function : Author

Hans-Otto Karnath

Function : Author

Ron Keren

Function : Author

Gregory Kuchcinski

Function : Author

Excellence Laboratory LabEx DISTALZ

Tobias Langheinrich

Function : Author

Thibaud Lebouvier

Function : Author
PersonId : 754049
IdHAL : thibaud-lebouvier
ORCID : 0000-0002-6630-394X
IdRef : 177112190

Excellence Laboratory LabEx DISTALZ

Maria João Leitão

Function : Author

Albert Lladó

Function : Author

Gemma Lombardi

Function : Author

Sandra Loosli

Function : Author

Carolina Maruta

Function : Author

Simon Mead

Function : Author

Lieke Meeter

Function : Author

Gabriel Miltenberger

Function : Author

Rick Van Minkelen

Function : Author

Sara Mitchell

Function : Author

Katrina Moore

Function : Author

Benedetta Nacmias

Function : Author

Annabel Nelson

Function : Author

Linn Öijerstedt

Function : Author

Jaume Olives

Function : Author

Sebastien Ourselin

Function : Author

Alessandro Padovani

Function : Author

Jessica Panman

Function : Author

Janne M Papma

Function : Author

Yolande Pijnenburg

Function : Author

Cristina Polito

Function : Author

Enrico Premi

Function : Author

Sara Prioni

Function : Author

Catharina Prix

Function : Author

Rosa Rademakers

Function : Author

Veronica Redaelli

Function : Author

Daisy Rinaldi

Function : Author

Institut du Cerveau = Paris Brain Institute

Tim Rittman

Function : Author

Ekaterina Rogaeva

Function : Author

Adeline Rollin

Function : Author

Excellence Laboratory LabEx DISTALZ

Pedro Rosa-Neto

Function : Author

Giacomina Rossi

Function : Author

Martin Rossor

Function : Author

Beatriz Santiago

Function : Author

Dario Saracino

Function : Author

Institut du Cerveau = Paris Brain Institute

Sabrina Sayah

Function : Author

Institut du Cerveau = Paris Brain Institute

Elio Scarpini

Function : Author

Sonja Schönecker

Function : Author

Elisa Semler

Function : Author

Rachelle Shafei

Function : Author

Christen Shoesmith

Function : Author

Imogen Swift

Function : Author

Miguel Tábuas-Pereira

Function : Author

Mikel Tainta

Function : Author

Ricardo Taipa

Function : Author

David Tang-Wai

Function : Author

David L Thomas

Function : Author

Paul Thompson

Function : Author

Hakan Thonberg

Function : Author

Carolyn Timberlake

Function : Author

Pietro Tiraboschi

Function : Author

Emily Todd

Function : Author

Philip Van Damme

Function : Author

Mathieu Vandenbulcke

Function : Author

Michele Veldsman

Function : Author

Ana Verdelho

Function : Author

Jorge Villanua

Function : Author

Carlo Wilke

Function : Author

Ione Woollacott

Function : Author

Elisabeth Wlasich

Function : Author

Henrik Zetterberg

Function : Author

Miren Zulaica

Function : Author

Abstract

Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3 T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia -not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.

Keywords

primary progressive aphasia GRN c9orf72 MAPT primary progressive aphasia GRN c9orf72 MAPT

Domains

Neurons and Cognition [q-bio.NC] Human genetics

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fcad036.pdf (5.95 Mo)

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https://hal.sorbonne-universite.fr/hal-04515740

Submitted on : Thursday, March 21, 2024-5:55:59 PM

Last modification on : Thursday, November 7, 2024-2:21:19 PM

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hal-04515740 , version 1 (21-03-2024)

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HAL Id : hal-04515740 , version 1
DOI : 10.1093/braincomms/fcad036

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Kiran Samra, Amy M Macdougall, Arabella Bouzigues, Martina Bocchetta, David M Cash, et al.. Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia. Brain Communications, 2023, 5, ⟨10.1093/braincomms/fcad036⟩. ⟨hal-04515740⟩

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Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia

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