Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort

Martina Bocchetta; Emily G Todd; Arabella Bouzigues; David M Cash; Jennifer M Nicholas; Rhian S Convery; Lucy L Russell; David L Thomas; Ian B Malone; Juan Eugenio Iglesias; John C van Swieten; Lize C Jiskoot; Harro Seelaar; Barbara Borroni; Daniela Galimberti; Raquel Sanchez-Valle; Robert Laforce; Fermin Moreno; Matthis Synofzik; Caroline Graff; Mario Masellis; Maria Carmela Tartaglia; James B Rowe; Rik Vandenberghe; Elizabeth Finger; Fabrizio Tagliavini; Alexandre de Mendonça; Isabel Santana; Chris R Butler; Simon Ducharme; Alexander Gerhard; Adrian Danek; Johannes Levin; Markus Otto; Sandro Sorbi; Isabelle Le Ber; Florence Pasquier; Jonathan D Rohrer; Aitana Sogorb Esteve; Annabel Nelson; Carolin Heller; Caroline V Greaves; Hanya Benotmane; Henrik Zetterberg; Imogen J Swift; Kiran Samra; Rachelle Shafei; Carolyn Timberlake; Thomas Cope; Timothy Rittman; Alberto Benussi; Enrico Premi; Roberto Gasparotti; Silvana Archetti; Stefano Gazzina; Valentina Cantoni; Andrea Arighi; Chiara Fenoglio; Elio Scarpini; Giorgio Fumagalli; Vittoria Borracci; Giacomina Rossi; Giorgio Giaccone; Giuseppe Di Fede; Paola Caroppo; Pietro Tiraboschi; Sara Prioni; Veronica Redaelli; David Tang-Wai; Ekaterina Rogaeva; Miguel Castelo-Branco; Morris Freedman; Ron Keren; Sandra Black; Sara Mitchell; Christen Shoesmith; Robart Bartha; Rosa Rademakers; Jackie Poos; Janne M Papma; Lucia Giannini; Rick van Minkelen; Yolande Pijnenburg; Benedetta Nacmias; Camilla Ferrari; Cristina Polito; Gemma Lombardi; Valentina Bessi; Michele Veldsman; Christin Andersson; Hakan Thonberg; Linn Öijerstedt; Vesna Jelic; Paul Thompson; Tobias Langheinrich; Albert Lladó; Anna Antonell; Jaume Olives; Mircea Balasa; Nuria Bargalló; Sergi Borrego-Ecija; Ana Verdelho; Carolina Maruta; Catarina B Ferreira; Gabriel Miltenberger; Frederico Simões Do Couto; Alazne Gabilondo; Ana Gorostidi; Jorge Villanua; Marta Cañada; Mikel Tainta; Miren Zulaica; Myriam Barandiaran; Patricia Alves; Benjamin Bender; Carlo Wilke; Lisa Graf; Annick Vogels; Mathieu Vandenbulcke; Philip van Damme; Rose Bruffaerts; Koen Poesen; Pedro Rosa-Neto; Serge Gauthier; Agnès Camuzat; Alexis Brice; Anne Bertrand; Aurélie Funkiewiez; Daisy Rinaldi; Dario Saracino; Olivier Colliot; Sabrina Sayah; Catharina Prix; Elisabeth Wlasich; Olivia Wagemann; Sandra Loosli; Sonja Schönecker; Tobias Hoegen; Jolina Lombardi; Sarah Anderl-Straub; Adeline Rollin; Gregory Kuchcinski; Maxime Bertoux; Thibaud Lebouvier; Vincent Deramecourt; Beatriz Santiago; Diana Duro; Maria João Leitão; Maria Rosario Almeida; Miguel Tábuas-Pereira; Sónia Afonso

doi:10.1093/braincomms/fcad061

Journal Articles Brain Communications Year : 2023

Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort

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Martina Bocchetta

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

UCL Institute of Neurology, Queen Square [London]

Brunel University London [Uxbridge]

Emily G Todd

Function : Author
PersonId : 1365752
ORCID : 0000-0003-1551-5691

UCL Institute of Neurology, Queen Square [London]

Arabella Bouzigues

Function : Author

UCL Institute of Neurology, Queen Square [London]

David M Cash

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

UCL Institute of Neurology, Queen Square [London]

University College of London [London]

Jennifer M Nicholas

Function : Author

London School of Hygiene and Tropical Medicine

Rhian S Convery

Function : Author

UCL Institute of Neurology, Queen Square [London]

Lucy L Russell

Function : Author

UCL Institute of Neurology, Queen Square [London]

David L Thomas

Function : Author

UCL Institute of Neurology, Queen Square [London]

UCL Queen Square Institute of Neurology

Ian B Malone

Function : Author
PersonId : 1365753
ORCID : 0000-0001-7512-7856

UCL Institute of Neurology, Queen Square [London]

Juan Eugenio Iglesias

Function : Author

Massachusetts General Hospital [Boston]

Harvard Medical School [Boston]

John C van Swieten

Function : Author

Erasmus University Medical Center [Rotterdam]

Lize C Jiskoot

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

Erasmus University Medical Center [Rotterdam]

Harro Seelaar

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

Erasmus University Medical Center [Rotterdam]

Barbara Borroni

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

Università degli Studi di Brescia = University of Brescia

Daniela Galimberti

Function : Author

Università degli Studi di Milano = University of Milan

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Raquel Sanchez-Valle

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

Institut d'Investigacions Biomèdiques August Pi i Sunyer

Robert Laforce

Function : Author

CHU de Québec–Université Laval

Fermin Moreno

Function : Author

Hospital Universitario Donostia [San Sebastian, Spain]

Matthis Synofzik

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

Hertie Institute for Clinical Brain Research [Tubingen]

German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen

Caroline Graff

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

Karolinska Institutet [Stockholm]

Karolinska University Hospital [Solna, Sweden]

Mario Masellis

Function : Author

Sunnybrook Research Institute [Toronto]

Maria Carmela Tartaglia

Function : Author

Tanz Center Research in Neurodegenerative Diseases [Toronto]

James B Rowe

Function : Author

Cambridge University Hospitals - NHS

University of Cambridge [UK]

Rik Vandenberghe

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

Catholic University of Leuven = Katholieke Universiteit Leuven

Elizabeth Finger

Function : Author

University of Western Ontario

Fabrizio Tagliavini

Function : Author

Fondazione IRCCS Istituto Neurologico "Carlo Besta"

Alexandre de Mendonça

Function : Author

Universidade de Lisboa = University of Lisbon = Université de Lisbonne

Isabel Santana

Function : Author

Chris R Butler

Function : Author

University of Oxford

Simon Ducharme

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

McGill University = Université McGill [Montréal, Canada]

Alexander Gerhard

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

Wolfson Molecular Imaging Centre

Universität Duisburg-Essen = University of Duisburg-Essen [Essen]

Adrian Danek

Function : Author
PersonId : 1355517
ORCID : 0000-0001-8857-5383

Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München

Johannes Levin

Function : Author

German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen

Munich Cluster of Systems Neurology

Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München

Markus Otto

Function : Author

Universitätsklinikum Ulm - University Hospital of Ulm

Sandro Sorbi

Function : Author

Università degli Studi di Firenze = University of Florence = Université de Florence

Fondazione Don Carlo Gnocchi

Isabelle Le Ber

Function : Author

Institut du Cerveau = Paris Brain Institute

CHU Pitié-Salpêtrière [AP-HP]

Florence Pasquier

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

Lille Neurosciences & Cognition - U 1172

Jonathan D Rohrer

Function : Author

UCL Institute of Neurology, Queen Square [London]

Aitana Sogorb Esteve

Function : Author

Annabel Nelson

Function : Author

Carolin Heller

Function : Author

Caroline V Greaves

Function : Author

Hanya Benotmane

Function : Author

Henrik Zetterberg

Function : Author

Imogen J Swift

Function : Author

Kiran Samra

Function : Author

Rachelle Shafei

Function : Author

Carolyn Timberlake

Function : Author

Thomas Cope

Function : Author

Timothy Rittman

Function : Author

Alberto Benussi

Function : Author

Enrico Premi

Function : Author

Roberto Gasparotti

Function : Author

Silvana Archetti

Function : Author

Stefano Gazzina

Function : Author

Valentina Cantoni

Function : Author

Andrea Arighi

Function : Author

Chiara Fenoglio

Function : Author

Elio Scarpini

Function : Author

Giorgio Fumagalli

Function : Author

Vittoria Borracci

Function : Author

Giacomina Rossi

Function : Author

Giorgio Giaccone

Function : Author

Giuseppe Di Fede

Function : Author

Paola Caroppo

Function : Author

Pietro Tiraboschi

Function : Author

Sara Prioni

Function : Author

Veronica Redaelli

Function : Author

David Tang-Wai

Function : Author

Ekaterina Rogaeva

Function : Author

Miguel Castelo-Branco

Function : Author

Morris Freedman

Function : Author

Ron Keren

Function : Author

Sandra Black

Function : Author

Sara Mitchell

Function : Author

Christen Shoesmith

Function : Author

Robart Bartha

Function : Author

Rosa Rademakers

Function : Author

Jackie Poos

Function : Author

Janne M Papma

Function : Author

Lucia Giannini

Function : Author

Rick van Minkelen

Function : Author

Yolande Pijnenburg

Function : Author

Benedetta Nacmias

Function : Author

Camilla Ferrari

Function : Author

Cristina Polito

Function : Author

Gemma Lombardi

Function : Author

Valentina Bessi

Function : Author

Michele Veldsman

Function : Author

Christin Andersson

Function : Author

Hakan Thonberg

Function : Author

Linn Öijerstedt

Function : Author

Vesna Jelic

Function : Author

Paul Thompson

Function : Author

Tobias Langheinrich

Function : Author

Albert Lladó

Function : Author

Anna Antonell

Function : Author

Jaume Olives

Function : Author

Mircea Balasa

Function : Author

Nuria Bargalló

Function : Author

Sergi Borrego-Ecija

Function : Author

Ana Verdelho

Function : Author

Carolina Maruta

Function : Author

Catarina B Ferreira

Function : Author

Gabriel Miltenberger

Function : Author

Frederico Simões Do Couto

Function : Author

Alazne Gabilondo

Function : Author

Ana Gorostidi

Function : Author

Jorge Villanua

Function : Author

Marta Cañada

Function : Author

Mikel Tainta

Function : Author

Miren Zulaica

Function : Author

Myriam Barandiaran

Function : Author

Patricia Alves

Function : Author

Benjamin Bender

Function : Author

Carlo Wilke

Function : Author

Lisa Graf

Function : Author

Annick Vogels

Function : Author

Mathieu Vandenbulcke

Function : Author

Philip van Damme

Function : Author

Rose Bruffaerts

Function : Author

Koen Poesen

Function : Author

Pedro Rosa-Neto

Function : Author

Serge Gauthier

Function : Author

Agnès Camuzat

Function : Author

Alexis Brice

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

Anne Bertrand

Function : Author

Aurélie Funkiewiez

Function : Author

Daisy Rinaldi

Function : Author

Dario Saracino

Function : Author

Olivier Colliot

Function : Author

Sabrina Sayah

Function : Author

Catharina Prix

Function : Author

Elisabeth Wlasich

Function : Author

Olivia Wagemann

Function : Author

Sandra Loosli

Function : Author

Sonja Schönecker

Function : Author

Tobias Hoegen

Function : Author

Jolina Lombardi

Function : Author

Sarah Anderl-Straub

Function : Author

Adeline Rollin

Function : Author

Gregory Kuchcinski

Function : Author

Maxime Bertoux

Function : Author

Thibaud Lebouvier

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

Vincent Deramecourt

Function : Author

Beatriz Santiago

Function : Author

Diana Duro

Function : Author

Maria João Leitão

Function : Author

Maria Rosario Almeida

Function : Author

Miguel Tábuas-Pereira

Function : Author

Sónia Afonso

Function : Author

Abstract

Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. Three hundred eighty-seven mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). The w-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as ‘normal’ or ‘abnormal’ based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the ‘normal’ and ‘abnormal’ groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 points in the GRN group as well as a statistically significant increase in the revised Cambridge Behavioural Inventory of up to 11 points in MAPT, 10 points in GRN, and 8 points in C9orf72 mutation carriers. Baseline regional brain abnormalities on MRI in presymptomatic mutation carriers are associated with different profiles of clinical progression over time. These results may be helpful to inform stratification of participants in future trials.

Keywords

genetic frontotemporal dementia MRI imaging brain volumetry diffusion imaging presymptomatic stage

Domains

Neurons and Cognition [q-bio.NC]

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https://hal.sorbonne-universite.fr/hal-04513763

Submitted on : Wednesday, March 20, 2024-6:49:37 PM

Last modification on : Thursday, November 7, 2024-2:22:07 PM

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hal-04513763 , version 1 (20-03-2024)

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HAL Id : hal-04513763 , version 1
DOI : 10.1093/braincomms/fcad061
PUBMED : 36970046
PUBMEDCENTRAL : PMC10036293

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Martina Bocchetta, Emily G Todd, Arabella Bouzigues, David M Cash, Jennifer M Nicholas, et al.. Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort. Brain Communications, 2023, 5 (2), pp.fcad061. ⟨10.1093/braincomms/fcad061⟩. ⟨hal-04513763⟩

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Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort

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