Temporal order of clinical and biomarker changes in familial frontotemporal dementia
Adam Staffaroni
,
Melanie Quintana
,
Barbara Wendelberger
,
Hilary Heuer
,
Lucy Russell
,
Yann Cobigo
,
Amy Wolf
,
Sheng-Yang Matt Goh
,
Leonard Petrucelli
,
Tania Gendron
,
Carolin Heller
,
Annie Clark
,
Jack Carson Taylor
,
Amy Wise
,
Elise Ong
,
Leah Forsberg
,
Danielle Brushaber
,
Julio Rojas
,
Lawren Vandevrede
,
Peter Ljubenkov
,
Joel Kramer
,
Kaitlin Casaletto
,
Brian Appleby
,
Yvette Bordelon
,
Hugo Botha
,
Bradford Dickerson
,
Kimiko Domoto-Reilly
,
Julie Fields
,
Tatiana Foroud
,
Ralitza Gavrilova
,
Daniel Geschwind
,
Nupur Ghoshal
,
Jill Goldman
,
Jonathon Graff-Radford
,
Neill Graff-Radford
,
Murray Grossman
,
Matthew Hall
,
Ging-Yuek Hsiung
,
Edward Huey
,
David Irwin
,
David Jones
,
Kejal Kantarci
,
Daniel Kaufer
,
David Knopman
,
Walter Kremers
,
Argentina Lario Lago
,
Maria Lapid
,
Maria Lapid
,
Irene Litvan
,
Diane Lucente
,
Ian Mackenzie
,
Mario Mendez
,
Mario Mendez
,
Carly Mester
,
Bruce Miller
,
Chiadi Onyike
,
Chiadi Onyike
,
Rosa Rademakers
,
Rosa Rademakers
,
Vijay Ramanan
,
Vijay Ramanan
,
Eliana Marisa Ramos
,
Meghana Rao
,
Katya Rascovsky
,
Katherine Rankin
,
Erik Roberson
,
Rodolfo Savica
,
M Carmela Tartaglia
,
Sandra Weintraub
,
Sandra Weintraub
,
Bonnie Wong
,
David Cash
,
Arabella Bouzigues
,
Imogen Swift
,
Georgia Peakman
,
Martina Bocchetta
,
Emily Todd
,
Rhian Convery
,
James Rowe
,
Barbara Borroni
,
Daniela Galimberti
,
Pietro Tiraboschi
,
Mario Masellis
,
Elizabeth Finger
,
John van Swieten
,
Harro Seelaar
,
Lize Jiskoot
,
Sandro Sorbi
,
Chris Butler
,
Caroline Graff
,
Alexander Gerhard
,
Tobias Langheinrich
,
Robert Laforce
,
Raquel Sanchez-Valle
,
Alexandre de Mendonça
,
Fermin Moreno
,
Matthis Synofzik
,
Rik Vandenberghe
,
Simon Ducharme
,
Isabelle Le Ber
(1)
,
Johannes Levin
,
Adrian Danek
,
Markus Otto
,
Florence Pasquier
,
Isabel Santana
,
John Kornak
,
Bradley Boeve
,
Bradley Boeve
,
Howard Rosen
,
Jonathan Rohrer
,
Adam. Boxer
,
M. Carmela Tartaglia
,
Adam. Boxer
,
Liana Apostolova
,
Sami Barmada
,
Andrea Bozoki
,
David Clark
,
Giovanni Coppola
,
Ryan Darby
,
Dennis Dickson
,
Kelley Faber
,
Anne Fagan
,
Douglas Galasko
,
Ian Grant
,
Eric Huang
,
Diana Kerwin
,
Suzee Lee
,
Gabriel Leger
,
Joseph Masdeux
,
Scott Mcginnis
,
M. Belen Pascual
,
Peter Pressman
,
Aaron Ritter
,
William Seeley
,
Jeremy Syrjanen
,
Jack Taylor
,
Aitana Sogorb Esteve
,
Annabel Nelson
,
Caroline Greaves
,
David Thomas
,
Hanya Benotmane
,
Henrik Zetterberg
,
Jennifer Nicholas
,
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
,
Sara Prioni
,
Veronica Redaelli
,
David Tang-Wai
,
Ekaterina Rogaeva
,
Miguel Castelo-Branco
,
Morris Freedman
,
Ron Keren
,
Sandra Black
,
Sara Mitchell
,
Christen Shoesmith
,
Robart Bartha
,
Jackie Poos
,
Janne 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
,
Albert Lladó
,
Anna Antonell
,
Jaume Olives
,
Mircea Balasa
,
Nuria Bargalló
,
Sergi Borrego-Ecija
,
Ana Verdelho
,
Carolina Maruta
,
Catarina 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
Adam Staffaroni
- Function : Author
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Melanie Quintana
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Barbara Wendelberger
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Hilary Heuer
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Lucy Russell
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Yann Cobigo
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Amy Wolf
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Sheng-Yang Matt Goh
- Function : Author
Leonard Petrucelli
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Tania Gendron
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Carolin Heller
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Annie Clark
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Jack Carson Taylor
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Amy Wise
- Function : Author
Elise Ong
- Function : Author
Leah Forsberg
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Danielle Brushaber
- Function : Author
Julio Rojas
- Function : Author
Lawren Vandevrede
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Peter Ljubenkov
- Function : Author
Joel Kramer
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Kaitlin Casaletto
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Brian Appleby
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Yvette Bordelon
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Hugo Botha
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Bradford Dickerson
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Kimiko Domoto-Reilly
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Julie Fields
- Function : Author
Tatiana Foroud
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Ralitza Gavrilova
- Function : Author
Daniel Geschwind
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Nupur Ghoshal
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- PersonId : 799133
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Jill Goldman
- Function : Author
Jonathon Graff-Radford
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Neill Graff-Radford
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Murray Grossman
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Matthew Hall
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Ging-Yuek Hsiung
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Edward Huey
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David Irwin
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David Jones
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Kejal Kantarci
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Daniel Kaufer
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David Knopman
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- PersonId : 1382711
- ORCID : 0000-0002-6544-066X
Walter Kremers
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Argentina Lario Lago
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Maria Lapid
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- ORCID : 0000-0002-1163-5584
Maria Lapid
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Irene Litvan
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- ORCID : 0000-0002-3485-3445
Diane Lucente
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Ian Mackenzie
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Mario Mendez
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- PersonId : 1382714
- ORCID : 0000-0001-6441-7989
Mario Mendez
- Function : Author
Carly Mester
- Function : Author
Bruce Miller
- Function : Author
Chiadi Onyike
- Function : Author
Chiadi Onyike
- Function : Author
Rosa Rademakers
- Function : Author
- PersonId : 1382715
- ORCID : 0000-0002-4049-0863
Rosa Rademakers
- Function : Author
Vijay Ramanan
- Function : Author
- PersonId : 1382716
- ORCID : 0000-0001-6591-8734
Vijay Ramanan
- Function : Author
Eliana Marisa Ramos
- Function : Author
Meghana Rao
- Function : Author
Katya Rascovsky
- Function : Author
Katherine Rankin
- Function : Author
Erik Roberson
- Function : Author
- PersonId : 1305795
- ORCID : 0000-0002-1810-9763
Rodolfo Savica
- Function : Author
M Carmela Tartaglia
- Function : Author
Sandra Weintraub
- Function : Author
Sandra Weintraub
- Function : Author
Bonnie Wong
- Function : Author
David Cash
- Function : Author
- PersonId : 1364325
- ORCID : 0000-0001-7833-616X
Arabella Bouzigues
- Function : Author
- PersonId : 1363147
- ORCID : 0000-0002-0267-8590
Imogen Swift
- Function : Author
Georgia Peakman
- Function : Author
- PersonId : 1343223
- ORCID : 0000-0002-3319-138X
Martina Bocchetta
- Function : Author
- PersonId : 1363148
- ORCID : 0000-0003-1814-5024
Emily Todd
- Function : Author
Rhian Convery
- Function : Author
James Rowe
- Function : Author
- PersonId : 1343226
- ORCID : 0000-0001-7216-8679
Barbara Borroni
- Function : Author
Daniela Galimberti
- Function : Author
- PersonId : 1305542
- ORCID : 0000-0002-9284-5953
Pietro Tiraboschi
- Function : Author
Mario Masellis
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Elizabeth Finger
- Function : Author
John van Swieten
- Function : Author
Harro Seelaar
- Function : Author
- PersonId : 1343222
- ORCID : 0000-0003-1989-7527
Lize Jiskoot
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Sandro Sorbi
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- PersonId : 1370731
- ORCID : 0000-0002-0380-6670
Chris Butler
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Caroline Graff
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Alexander Gerhard
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- ORCID : 0000-0002-8071-6062
Tobias Langheinrich
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Robert Laforce
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Raquel Sanchez-Valle
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Alexandre de Mendonça
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Fermin Moreno
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Matthis Synofzik
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Rik Vandenberghe
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Simon Ducharme
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Johannes Levin
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Adrian Danek
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Markus Otto
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Florence Pasquier
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Isabel Santana
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John Kornak
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Bradley Boeve
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- PersonId : 1275781
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Bradley Boeve
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Howard Rosen
- Function : Author
Jonathan Rohrer
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Adam. Boxer
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- PersonId : 1382718
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M. Carmela Tartaglia
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Adam. Boxer
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Liana Apostolova
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Sami Barmada
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Andrea Bozoki
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David Clark
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Giovanni Coppola
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Ryan Darby
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Dennis Dickson
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Kelley Faber
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Anne Fagan
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Douglas Galasko
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Ian Grant
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Eric Huang
- Function : Author
Diana Kerwin
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Suzee Lee
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Gabriel Leger
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Joseph Masdeux
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Scott Mcginnis
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M. Belen Pascual
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Peter Pressman
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Aaron Ritter
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William Seeley
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Jeremy Syrjanen
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Jack Taylor
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Aitana Sogorb Esteve
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Annabel Nelson
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Caroline Greaves
- Function : Author
David Thomas
- Function : Author
Hanya Benotmane
- Function : Author
Henrik Zetterberg
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Jennifer Nicholas
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Kiran Samra
- Function : Author
Rachelle Shafei
- Function : Author
Carolyn Timberlake
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Thomas Cope
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Timothy Rittman
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Alberto Benussi
- Function : Author
Enrico Premi
- Function : Author
Roberto Gasparotti
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Silvana Archetti
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Stefano Gazzina
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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
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
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Christen Shoesmith
- Function : Author
Robart Bartha
- Function : Author
Jackie Poos
- Function : Author
Janne 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
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
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Carolina Maruta
- Function : Author
Catarina Ferreira
- Function : Author
Gabriel Miltenberger
- Function : Author
Frederico Simões Do Couto
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Alazne Gabilondo
- Function : Author
Ana Gorostidi
- Function : Author
Jorge Villanua
- Function : Author
Marta Cañada
- Function : Author
Mikel Tainta
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Miren Zulaica
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Myriam Barandiaran
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Patricia Alves
- Function : Author
Benjamin Bender
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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
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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
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- 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
Unlike familial Alzheimer's disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72, GRN and MAPT mutation carriers. Models included longitudinal clinical and neuropsychological scores, regional brain volumes and plasma neurofilament light chain (NfL) in 796 carriers and 412 noncarrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations using model-based patient selection, atrophy and NfL were the best endpoints, whereas clinical measures were potential endpoints in early symptomatic trials. f-FTD prevention trials are feasible but will likely require global recruitment efforts. These disease progression models will facilitate the planning of f-FTD clinical trials, including the selection of optimal endpoints and enrollment criteria to maximize power to detect treatment effects.