Evidence map›Paper›PMID 36138153›Full record

ArticleNature medicine2022

Temporal order of clinical and biomarker changes in familial frontotemporal dementia.

Adam M Staffaroni, Melanie Quintana, Barbara Wendelberger, Hilary W Heuer, Lucy L Russell, Yann Cobigo, Amy Wolf, Sheng-Yang Matt Goh, Leonard Petrucelli, Tania F Gendron and 95 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 2 pooled it
15.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  4. Observational
  5. Article
  6. Article
  7. Do amyloid trajectories reach a ceiling? Evidence from iterative approximation and simulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Composite grey matter fingerprints for genetic frontotemporal dementia.Journal of neurology, neurosurgery, and psychiatry · 2026
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

105 authors at 20 institutions in 11 countries.

Adam M StaffaroniDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. adam.staffaroni@ucsf.edu.ORCID http://orcid.org/0000-0002-3903-9805
Melanie QuintanaBerry Consultants, Austin, TX, USA.ORCID http://orcid.org/0000-0002-1763-2704
Barbara WendelbergerBerry Consultants, Austin, TX, USA.ORCID http://orcid.org/0000-0003-4426-9602
Hilary W HeuerDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Lucy L RussellDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.ORCID http://orcid.org/0000-0001-5023-5893
Yann CobigoDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0354-4092
Amy WolfDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Sheng-Yang Matt GohDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Leonard PetrucelliDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Tania F GendronDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0002-7335-2627
Carolin HellerDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.ORCID http://orcid.org/0000-0002-1934-6162
Annie L ClarkDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Jack Carson TaylorDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6431-9956
Amy WiseDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Elise OngDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Leah ForsbergDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Danielle BrushaberDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Julio C RojasDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Lawren VandeVredeDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8304-6711
Peter LjubenkovDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Joel KramerDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Kaitlin B CasalettoDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Brian ApplebyDepartment of Neurology, Case Western Reserve University, Cleveland, OH, USA.
Yvette BordelonDepartment of Neurology, University of California, Los Angeles, Los Angeles, USA.
Hugo BothaDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-4390-685X
Bradford C DickersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Kimiko Domoto-ReillyDepartment of Neurology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7396-1633
Julie A FieldsDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Tatiana ForoudIndiana University School of Medicine, National Centralized Repository for Alzheimer's, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-5549-2212
Ralitza GavrilovaDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Daniel GeschwindDepartment of Neurology, University of California, Los Angeles, Los Angeles, USA.ORCID http://orcid.org/0000-0003-2896-3450
Nupur GhoshalDepartments of Neurology and Psychiatry, Washington University School of Medicine, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6680-6731
Jill GoldmanDepartment of Neurology, Columbia University, New York, NY, USA.
Jonathon Graff-RadfordDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Neill Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Murray GrossmanDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Matthew G H HallDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Ging-Yuek HsiungDivision of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-8017-0856
Edward D HueyDepartment of Neurology, Columbia University, New York, NY, USA.
David IrwinDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
David T JonesDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4807-9833
Kejal KantarciDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Daniel KauferDepartment of Neurology, University of North Carolina, Chapel Hill, NC, USA.
David KnopmanDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-6544-066X
Walter KremersDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Argentina Lario LagoDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Maria I LapidDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-1163-5584
Irene LitvanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-3485-3445
Diane LucenteDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ian R MackenzieDepartment of Pathology, University of British Columbia, Vancouver, British Columbia, Canada.
Mario F MendezDepartment of Neurology, University of California, Los Angeles, Los Angeles, USA.ORCID http://orcid.org/0000-0001-6441-7989
Carly MesterDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Bruce L MillerDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Rosa RademakersDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0002-4049-0863
Vijay K RamananDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-6591-8734
Eliana Marisa RamosDepartment of Neurology, University of California, Los Angeles, Los Angeles, USA.
Meghana RaoDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Katya RascovskyDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Katherine P RankinDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Erik D RobersonDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID http://orcid.org/0000-0002-1810-9763
Rodolfo SavicaDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
M Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-5944-8497
Sandra WeintraubDepartment of Neurology, Northwestern University, Chicago, IL, USA.
Bonnie WongDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
David M CashDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.ORCID http://orcid.org/0000-0001-7833-616X
Arabella BouziguesDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.ORCID http://orcid.org/0000-0002-0267-8590
Imogen J SwiftDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.
Georgia PeakmanDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.ORCID http://orcid.org/0000-0002-3319-138X
Martina BocchettaDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.ORCID http://orcid.org/0000-0003-1814-5024
Emily G ToddDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.
Rhian S ConveryDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.
James B RoweDepartment of Clinical Neurosciences and Cambridge University Hospitals NHS Trust and Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7216-8679
Barbara BorroniCentre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Daniela GalimbertiDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0002-9284-5953
Pietro TiraboschiFondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Mario MasellisDivision of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Elizabeth FingerDepartment of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada.
John C van SwietenDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.
Harro SeelaarDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.ORCID http://orcid.org/0000-0003-1989-7527
Lize C JiskootDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.
Sandro SorbiDepartment of Neurofarba, University of Florence, Florence, Italy.ORCID http://orcid.org/0000-0002-0380-6670
Chris R ButlerNuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Caroline GraffCenter for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet, Solna, Sweden.
Alexander GerhardDivision of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-8071-6062
Tobias LangheinrichDivision of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-4714-8657
Robert LaforceClinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, Québec City, Québec, Canada.ORCID http://orcid.org/0000-0002-2031-490X
Raquel Sanchez-ValleAlzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0001-7750-896X
Alexandre de MendonçaFaculty of Medicine, University of Lisbon, Lisbon, Portugal.
Fermin MorenoCognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain.
Matthis SynofzikDepartment of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Simon DucharmeDouglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada.
Isabelle Le BerSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France.
Johannes LevinNeurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, Germany.
Adrian DanekNeurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, Germany.ORCID http://orcid.org/0000-0001-8857-5383
Markus OttoDepartment of Neurology, University of Ulm, Ulm, Germany.
Florence PasquierUniversity of Lille, Lille, France.ORCID http://orcid.org/0000-0001-9880-9788
Isabel SantanaNeurology Service, Faculty of Medicine, University Hospital of Coimbra (HUC), University of Coimbra, Coimbra, Portugal.
John KornakDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4153-8187
Howard J RosenDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Jonathan D RohrerDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square London, London, UK.
Adam L BoxerDepartment of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. adam.boxer@ucsf.edu.ORCID http://orcid.org/0000-0002-1215-5064
Frontotemporal Dementia Prevention Initiative (FPI) Investigators
University of California, San Francisco · USUK Dementia Research Institute · GBMayo Clinic in Arizona · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITBiogipuzkoa Health Research Institute · ESCentre National de la Recherche Scientifique · FRErasmus University Rotterdam · NLLudwig-Maximilians-Universität München · DEUniversity of Brescia · ITMayo Clinic in Florida · USUniversitat de Barcelona · ESUniversity of California, Los Angeles · USUniversity of Coimbra · PTUniversité de Lille · FRUniversity of Florence · ITUniversity of Lisbon · PTFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITHarvard University · USKarolinska Institutet · SEKU Leuven · BE

Funding

Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI Bradley F Boeve · 2019 to 2026
$120.9M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Thomas J. Grabowski · 2020 to 2026
$29.0M
Research Education Core FP30AG072977 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SANDRA WEINTRAUB · 2021 to 2026
$26.3M
The Four Repeat Tauopathy Neuroimaging InitiativeR01AG038791 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOXER, ADAM L. · 2010 to 2020
$18.1M
Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS)U01AG045390 · NIA · MAYO CLINIC ROCHESTER · PI BOEVE, BRADLEY F, ROSEN, HOWARD J · 2014 to 2018
$16.9M
The Frontotemporal Lobar Degeneration Neuroimaging InitiativeR01AG032306 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSEN, HOWARD J · 2009 to 2013
$10.0M
Department of Health BRC-1215-20014Department of Health BRC149/NS/MHMedical Research Council MR/K010395/1Medical Research Council MR/M008525/1Medical Research Council MR/M023664/1Medical Research Council MR/T046015/1Medical Research Council SUAG/092 G116768NIA NIH HHS K23 AG059888NIA NIH HHS K23 AG061253NIA NIH HHS K23 AG073514NIA NIH HHS K24 AG045333NIA NIH HHS L30 AG069301NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG072977NIA NIH HHS R01 AG029577NIA NIH HHS R01 AG032306NIA NIH HHS R01 AG038791NIA NIH HHS R01 AG058233NIA NIH HHS RF1 AG029577NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG045390NIA NIH HHS U19 AG063911NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG072122NICHD NIH HHS K12 HD001459NINDS NIH HHS U54 NS092089Wellcome Trust 220258
6 · The paper itself

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.

Indexed as

Frontotemporal DementiaBiomarkersC9orf72 ProteinClinical Trials as TopicDisease ProgressionHumansMutationtau ProteinsBiomarkersC9orf72 Proteintau Proteins

Identifiers

PMID36138153
PMCPMC9951811
OpenAlexW4296690345

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.