Temporal order of clinical and biomarker changes in familial frontotemporal dementia.
Staffaroni Adam M, Quintana Melanie, Wendelberger Barbara, Heuer Hilary W, Russell Lucy L, Cobigo Yann, Wolf Amy, Goh Sheng-Yang Matt, Petrucelli Leonard, Gendron Tania F, Heller Carolin, Clark Annie L, Taylor Jack Carson, Wise Amy, Ong Elise, Forsberg Leah, Brushaber Danielle, Rojas Julio C, VandeVrede Lawren, Ljubenkov Peter, Kramer Joel, Casaletto Kaitlin B, Appleby Brian, Bordelon Yvette, Botha Hugo, Dickerson Bradford C, Domoto-Reilly Kimiko, Fields Julie A, Foroud Tatiana, Gavrilova Ralitza, Geschwind Daniel, Ghoshal Nupur, Goldman Jill, Graff-Radford Jonathon, Graff-Radford Neill, Grossman Murray, Hall Matthew G H, Hsiung Ging-Yuek, Huey Edward D, Irwin David, Jones David T, Kantarci Kejal, Kaufer Daniel, Knopman David, Kremers Walter, Lago Argentina Lario, Lapid Maria I, Litvan Irene, Lucente Diane, Mackenzie Ian R, Mendez Mario F, Mester Carly, Miller Bruce L, Onyike Chiadi U, Rademakers Rosa, Ramanan Vijay K, Ramos Eliana Marisa, Rao Meghana, Rascovsky Katya, Rankin Katherine P, Roberson Erik D, Savica Rodolfo, Tartaglia M Carmela, Weintraub Sandra, Wong Bonnie, Cash David M, Bouzigues Arabella, Swift Imogen J, Peakman Georgia, Bocchetta Martina, Todd Emily G, Convery Rhian S, Rowe James B, Borroni Barbara, Galimberti Daniela, Tiraboschi Pietro, Masellis Mario, Finger Elizabeth, van Swieten John C, Seelaar Harro, Jiskoot Lize C, Sorbi Sandro, Butler Chris R, Graff Caroline, Gerhard Alexander, Langheinrich Tobias, Laforce Robert, Sanchez-Valle Raquel, de Mendonça Alexandre, Moreno Fermin, Synofzik Matthis, Vandenberghe Rik, Ducharme Simon, Le Ber Isabelle, Levin Johannes, Danek Adrian, Otto Markus, Pasquier Florence, Santana Isabel, Kornak John, Boeve Bradley F, Rosen Howard J, Rohrer Jonathan D, Boxer Adam L, Frontotemporal Dementia Prevention Initiative (FPI) Investigators
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Аннотация
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.
Для цитирования: Staffaroni Adam M, Quintana Melanie, Wendelberger Barbara, Heuer Hilary W, Russell Lucy L, Cobigo Yann, Wolf Amy, Goh Sheng-Yang Matt, Petrucelli Leonard, Gendron Tania F, Heller Carolin, Clark Annie L, Taylor Jack Carson, Wise Amy, Ong Elise, Forsberg Leah, Brushaber Danielle, Rojas Julio C, VandeVrede Lawren, Ljubenkov Peter, Kramer Joel, Casaletto Kaitlin B, Appleby Brian, Bordelon Yvette, Botha Hugo, Dickerson Bradford C, Domoto-Reilly Kimiko, Fields Julie A, Foroud Tatiana, Gavrilova Ralitza, Geschwind Daniel, Ghoshal Nupur, Goldman Jill, Graff-Radford Jonathon, Graff-Radford Neill, Grossman Murray, Hall Matthew G H, Hsiung Ging-Yuek, Huey Edward D, Irwin David, Jones David T, Kantarci Kejal, Kaufer Daniel, Knopman David, Kremers Walter, Lago Argentina Lario, Lapid Maria I, Litvan Irene, Lucente Diane, Mackenzie Ian R, Mendez Mario F, Mester Carly, Miller Bruce L, Onyike Chiadi U, Rademakers Rosa, Ramanan Vijay K, Ramos Eliana Marisa, Rao Meghana, Rascovsky Katya, Rankin Katherine P, Roberson Erik D, Savica Rodolfo, Tartaglia M Carmela, Weintraub Sandra, Wong Bonnie, Cash David M, Bouzigues Arabella, Swift Imogen J, Peakman Georgia, Bocchetta Martina, Todd Emily G, Convery Rhian S, Rowe James B, Borroni Barbara, Galimberti Daniela, Tiraboschi Pietro, Masellis Mario, Finger Elizabeth, van Swieten John C, Seelaar Harro, Jiskoot Lize C, Sorbi Sandro, Butler Chris R, Graff Caroline, Gerhard Alexander, Langheinrich Tobias, Laforce Robert, Sanchez-Valle Raquel, de Mendonça Alexandre, Moreno Fermin, Synofzik Matthis, Vandenberghe Rik, Ducharme Simon, Le Ber Isabelle, Levin Johannes, Danek Adrian, Otto Markus, Pasquier Florence, Santana Isabel, Kornak John, Boeve Bradley F, Rosen Howard J, Rohrer Jonathan D, Boxer Adam L, Frontotemporal Dementia Prevention Initiative (FPI) Investigators. Temporal order of clinical and biomarker changes in familial frontotemporal dementia.. Nature medicine. 2022. DOI: 10.1038/s41591-022-01942-9.
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