Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort - Sorbonne Université Access content directly
Journal Articles Brain Communications Year : 2023

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

Martina Bocchetta (1, 2) , Emily G Todd (1) , Arabella Bouzigues (1) , David M Cash (1, 3) , Jennifer M Nicholas (4) , Rhian S Convery (1) , Lucy L Russell (1) , David L Thomas (1, 5) , Ian B Malone (1) , Juan Eugenio Iglesias (6, 7) , John C van Swieten (8) , Lize C Jiskoot (8) , Harro Seelaar (8) , Barbara Borroni (9) , Daniela Galimberti (10, 11) , Raquel Sanchez-Valle (12) , Robert Laforce (13) , Fermin Moreno (14) , Matthis Synofzik (15, 16) , Caroline Graff (17, 18) , Mario Masellis (19) , Maria Carmela Tartaglia (20) , James B Rowe (21, 22) , Rik Vandenberghe (23) , Elizabeth Finger (24) , Fabrizio Tagliavini (25) , Alexandre de Mendonça (26) , Isabel Santana , Chris R Butler (27) , Simon Ducharme (28) , Alexander Gerhard (29, 30) , Adrian Danek (31) , Johannes Levin (16, 32, 31) , Markus Otto (33) , Sandro Sorbi (34, 35) , Isabelle Le Ber (36, 37) , Florence Pasquier (38) , Jonathan D Rohrer (1) , 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
1 UCL Institute of Neurology, Queen Square [London]
2 Brunel University London [Uxbridge]
3 UCL - University College of London [London]
4 LSHTM - London School of Hygiene and Tropical Medicine
5 UCL Queen Square Institute of Neurology
6 Massachusetts General Hospital [Boston]
7 HMS - Harvard Medical School [Boston]
8 Erasmus MC - Erasmus University Medical Center [Rotterdam]
9 UniBs - Università degli Studi di Brescia = University of Brescia
10 UNIMI - Università degli Studi di Milano = University of Milan
11 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
12 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
13 CHU de Québec–Université Laval
14 HUD - Hospital Universitario Donostia [San Sebastian, Spain]
15 Hertie Institute for Clinical Brain Research [Tubingen]
16 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
17 Karolinska Institutet [Stockholm]
18 KUH - Karolinska University Hospital [Solna, Sweden]
19 SRI - Sunnybrook Research Institute [Toronto]
20 Tanz Center Research in Neurodegenerative Diseases [Toronto]
21 CUH - Cambridge University Hospitals - NHS
22 CAM - University of Cambridge [UK]
23 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
24 UWO - University of Western Ontario
25 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
26 ULISBOA - Universidade de Lisboa = University of Lisbon
27 University of Oxford
28 McGill University = Université McGill [Montréal, Canada]
29 WMIC - Wolfson Molecular Imaging Centre
30 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
31 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
32 SyNery - Munich Cluster of Systems Neurology
33 Universitätsklinikum Ulm - University Hospital of Ulm
34 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence
35 Fondazione Don Carlo Gnocchi
36 ICM - Institut du Cerveau = Paris Brain Institute
37 CHU Pitié-Salpêtrière [AP-HP]
38 LilNCog - Lille Neurosciences & Cognition - U 1172
Isabel Santana
  • Function : Author
Florence Pasquier
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
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
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.
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hal-04513763 , version 1 (20-03-2024)

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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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