Temporal order of clinical and biomarker changes in familial frontotemporal dementia

dc.contributor.authorStaffaroni, Adam M.
dc.contributor.authorQuintana, Melanie
dc.contributor.authorWendelberger, Barbara
dc.contributor.authorHeuer, Hilary W.
dc.contributor.authorRussell, Lucy L.
dc.contributor.authorCobigo, Yann
dc.contributor.authorWolf, Amy
dc.contributor.authorGoh, Sheng-Yang Matt
dc.contributor.authorPetrucelli, Leonard
dc.contributor.authorGendron, Tania F.
dc.contributor.authorHeller, Carolin
dc.contributor.authorClark, Annie L.
dc.contributor.authorTaylor, Jack Carson
dc.contributor.authorWise, Amy
dc.contributor.authorOng, Elise
dc.contributor.authorForsberg, Leah
dc.contributor.authorBrushaber, Danielle
dc.contributor.authorRojas, Julio C.
dc.contributor.authorVandeVrede, Lawren
dc.contributor.authorLjubenkov, Peter
dc.contributor.authorKramer, Joel
dc.contributor.authorCasaletto, Kaitlin B.
dc.contributor.authorAppleby, Brian
dc.contributor.authorBordelon, Yvette
dc.contributor.authorBotha, Hugo
dc.contributor.authorDickerson, Bradford C.
dc.contributor.authorDomoto-Reilly, Kimiko
dc.contributor.authorFields, Julie A.
dc.contributor.authorForoud, Tatiana
dc.contributor.authorGavrilova, Ralitza
dc.contributor.authorGeschwind, Daniel
dc.contributor.authorGhoshal, Nupur
dc.contributor.authorGoldman, Jill
dc.contributor.authorGraff-Radford, Jonathon
dc.contributor.authorGraff-Radford, Neill
dc.contributor.authorGrossman, Murray
dc.contributor.authorHall, Matthew G. H.
dc.contributor.authorHsiung, Ging-Yuek
dc.contributor.authorHuey, Edward D.
dc.contributor.authorIrwin, David
dc.contributor.authorJones, David T.
dc.contributor.authorKantarci, Kejal
dc.contributor.authorKaufer, Daniel
dc.contributor.authorKnopman, David
dc.contributor.authorKremers, Walter
dc.contributor.authorLago, Argentina Lario
dc.contributor.authorLapid, Maria I.
dc.contributor.authorLitvan, Irene
dc.contributor.authorLucente, Diane
dc.contributor.authorMackenzie, Ian R.
dc.contributor.authorMendez, Mario F.
dc.contributor.authorMester, Carly
dc.contributor.authorMiller, Bruce L.
dc.contributor.authorOnyike, Chiadi U.
dc.contributor.authorRademakers, Rosa
dc.contributor.authorRamanan, Vijay K.
dc.contributor.authorRamos, Eliana Marisa
dc.contributor.authorRao, Meghana
dc.contributor.authorRascovsky, Katya
dc.contributor.authorRankin, Katherine P.
dc.contributor.authorRoberson, Erik D.
dc.contributor.authorSavica, Rodolfo
dc.contributor.authorTartaglia, M. Carmela
dc.contributor.authorWeintraub, Sandra
dc.contributor.authorWong, Bonnie
dc.contributor.authorCash, David M.
dc.contributor.authorBouzigues, Arabella
dc.contributor.authorSwift, Imogen J.
dc.contributor.authorPeakman, Georgia
dc.contributor.authorBocchetta, Martina
dc.contributor.authorTodd, Emily G.
dc.contributor.authorConvery, Rhian S.
dc.contributor.authorRowe, James B.
dc.contributor.authorBorroni, Barbara
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorTiraboschi, Pietro
dc.contributor.authorMasellis, Mario
dc.contributor.authorFinger, Elizabeth
dc.contributor.authorvan Swieten, John C.
dc.contributor.authorSeelaar, Harro
dc.contributor.authorJiskoot, Lize C.
dc.contributor.authorSorbi, Sandro
dc.contributor.authorButler, Chris R.
dc.contributor.authorGraff, Caroline
dc.contributor.authorGerhard, Alexander
dc.contributor.authorLangheinrich, Tobias
dc.contributor.authorLaforce, Robert
dc.contributor.authorSanchez-Valle, Raquel
dc.contributor.authorde Mendonça, Alexandre
dc.contributor.authorMoreno, Fermin
dc.contributor.authorSynofzik, Matthis
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorDucharme, Simon
dc.contributor.authorLe Ber, Isabelle
dc.contributor.authorLevin, Johannes
dc.contributor.authorDanek, Adrian
dc.contributor.authorOtto, Markus
dc.contributor.authorPasquier, Florence
dc.contributor.authorSantana, Isabel
dc.contributor.authorKornak, John
dc.contributor.authorBoeve, Bradley F.
dc.contributor.authorRosen, Howard J.
dc.contributor.authorRohrer, Jonathan D.
dc.contributor.authorBoxer, Adam L.
dc.contributor.authorFrontotemporal Dementia Prevention Initiative (FPI) Investigators
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2023-12-21T13:03:04Z
dc.date.available2023-12-21T13:03:04Z
dc.date.issued2022
dc.description.abstractUnlike 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 non-carrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations employing 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.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationStaffaroni AM, Quintana M, Wendelberger B, et al. Temporal order of clinical and biomarker changes in familial frontotemporal dementia. Nat Med. 2022;28(10):2194-2206. doi:10.1038/s41591-022-01942-9
dc.identifier.urihttps://hdl.handle.net/1805/37483
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41591-022-01942-9
dc.relation.journalNature Medicine
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectFrontotemporal lobar degeneration
dc.subjectC9orf72
dc.subjectGRN
dc.subjectMAPT
dc.subjectDisease progression
dc.subjectNeurofilament light chain
dc.subjectNeuroimaging
dc.subjectNeuropsychology
dc.subjectClinical trials
dc.titleTemporal order of clinical and biomarker changes in familial frontotemporal dementia
dc.typeArticle
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