| Literature DB >> 36138153 |
Adam M Staffaroni1, Melanie Quintana2, Barbara Wendelberger2, Hilary W Heuer3, Lucy L Russell4, Yann Cobigo3, Amy Wolf3, Sheng-Yang Matt Goh3, Leonard Petrucelli5, Tania F Gendron5, Carolin Heller4, Annie L Clark3, Jack Carson Taylor3, Amy Wise3, Elise Ong3, Leah Forsberg6, Danielle Brushaber7, Julio C Rojas3, Lawren VandeVrede3, Peter Ljubenkov3, Joel Kramer3, Kaitlin B Casaletto3, Brian Appleby8, Yvette Bordelon9, Hugo Botha6, Bradford C Dickerson10, Kimiko Domoto-Reilly11, Julie A Fields12, Tatiana Foroud13, Ralitza Gavrilova6, Daniel Geschwind9,14, Nupur Ghoshal15, Jill Goldman16, Jonathon Graff-Radford6, Neill Graff-Radford17, Murray Grossman18, Matthew G H Hall3, Ging-Yuek Hsiung19, Edward D Huey16, David Irwin18, David T Jones6, Kejal Kantarci6, Daniel Kaufer20, David Knopman6, Walter Kremers7, Argentina Lario Lago3, Maria I Lapid12, Irene Litvan21, Diane Lucente10, Ian R Mackenzie22, Mario F Mendez9, Carly Mester7, Bruce L Miller3, Chiadi U Onyike23, Rosa Rademakers5,24,25, Vijay K Ramanan6, Eliana Marisa Ramos9, Meghana Rao6, Katya Rascovsky18, Katherine P Rankin3, Erik D Roberson26, Rodolfo Savica6, M Carmela Tartaglia27, Sandra Weintraub28, Bonnie Wong10, David M Cash4, Arabella Bouzigues4, Imogen J Swift4, Georgia Peakman4, Martina Bocchetta4, Emily G Todd4, Rhian S Convery4, James B Rowe29, Barbara Borroni30, Daniela Galimberti31,32, Pietro Tiraboschi33, Mario Masellis34, Elizabeth Finger35, John C van Swieten36, Harro Seelaar36, Lize C Jiskoot36, Sandro Sorbi37,38, Chris R Butler39,40, Caroline Graff41,42, Alexander Gerhard43,44, Tobias Langheinrich43,45, Robert Laforce46, Raquel Sanchez-Valle47, Alexandre de Mendonça48, Fermin Moreno49,50, Matthis Synofzik51,52, Rik Vandenberghe53,54,55, Simon Ducharme56,57, Isabelle Le Ber58,59,60, Johannes Levin61,62,63, Adrian Danek61, Markus Otto64, Florence Pasquier65,66,67, Isabel Santana68,69, John Kornak70, Bradley F Boeve6, Howard J Rosen3, Jonathan D Rohrer4, Adam L Boxer71.
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.Entities:
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Year: 2022 PMID： 36138153 DOI： 10.1038/s41591-022-01942-9
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 87.241