Evidence map›Paper›PMID 41068257›Full record

ArticleMolecular psychiatry2025

Cortical microstructure is associated with disease severity and clinical progression in genetic frontotemporal dementia: a GENFI study.

Elena Rodriguez-Vieitez, Melissa T Rydell, Abbe Ullgren, Victor Montal, Ignacio Illán-Gala, Juan Fortea, Vesna Jelic, Arabella Bouzigues, Lucy L Russell, Phoebe H Foster and 30 more

Abstract read
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

40 authors.

Elena Rodriguez-VieitezDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden. elena.rodriguez-vieitez@ki.se.ORCID 0000-0002-6639-8141
Melissa T RydellDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Abbe UllgrenDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Victor MontalBarcelona Supercomputing Center, Barcelona, Spain.
Ignacio Illán-GalaSant Pau Memory Unit, Neurology Department, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Juan ForteaSant Pau Memory Unit, Neurology Department, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0002-1340-638X
Vesna JelicDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Arabella BouziguesDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-0267-8590
Lucy L RussellDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Phoebe H FosterDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Eve Ferry-BolderDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
John C van SwietenDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.
Lize C JiskootDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.
Harro SeelaarDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.ORCID 0000-0003-1989-7527
Raquel Sanchez-ValleAlzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
Robert LaforceClinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, Québec City, QC, Canada.
Daniela GalimbertiFondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0002-9284-5953
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.ORCID 0000-0001-6237-2502
Alexandre de MendonçaFaculty of Medicine, University of Lisbon, Lisbon, Portugal.
Pietro TiraboschiDivision of Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Isabel SantanaFaculty of Medicine, University of Coimbra, Coimbra, Portugal.
Alexander GerhardDivision of Psychology Communication and Human Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.
Johannes LevinDepartment of Neurology, Ludwig-Maximilians-University, Munich, Germany.
Sandro SorbiDepartment of Neurofarba, University of Florence, Florence, Italy.ORCID 0000-0002-0380-6670
Markus OttoDepartment of Neurology, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0003-4273-4267
Florence PasquierUniversity of Lille and INSERM 1172, Lille, France.ORCID 0000-0001-9880-9788
Simon DucharmeDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.ORCID 0000-0002-7309-1113
Chris R ButlerDepartment of Brain Sciences, Imperial College London, London, UK.ORCID 0000-0002-7502-9284
Isabelle Le BerSorbonne Université, Paris Brain Institute, Institut du Cerveau - ICM, Inserm U1127, Pitié-Salpêtrière, Paris, France.
Elizabeth FingerDepartment of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
Maria Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-5944-8497
Mario MasellisSunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
James B RoweDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID 0000-0001-7216-8679
Matthis SynofzikDepartment of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.ORCID 0000-0002-2280-7273
Fermin MorenoCognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain.ORCID 0000-0001-5200-3164
Barbara BorroniDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Jonathan D RohrerDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Eric WestmanDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3115-2977
Caroline GraffDepartment of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden. caroline.graff@ki.se.ORCID 0000-0002-9949-2951
Genetic Frontotemporal Dementia Initiative (GENFI)

Funding

Alzheimerfonden AF-939647, AF-968569, AF-1012445Karolinska Institutet (Karolinska Institute) KI Fonder grantsMinistry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) PI21/00791 and PI24/00598Neuroförbundet (Swedish Association of Persons with Neurological Disabilities) F2022-0036, F2023-0049, F2024-0064Stockholms Läns Landsting (Stockholm County Council) ALF grants FoUI-960437, FoUI-975492
6 · The paper itself

Abstract

The study of genetic frontotemporal dementia (FTD) allows investigating its earliest presymptomatic stages. Using cross-sectional T1-weighted and diffusion-weighted MRI, we test the hypothesis that cortical microstructural alterations, quantified as cortical mean diffusivity (cMD), are detectable earlier and are more strongly associated with clinical progression than cortical thickness (CTh). The sample comprised n = 710 individuals (47.8 ± 13.5 years, 56.6% female, 14.1 ± 3.3 years of education), including 118 symptomatic carriers and 305 presymptomatic carriers with mutations in C9orf72, GRN or MAPT genes, and 287 non-carriers, collected from 24 GENFI sites. A subset of n = 453 individuals (289 carriers, 164 non-carriers) were investigated across Clinical Dementia Rating (CDR) = 0, 0.5 and ≥1 stages. Two subsets had longitudinal clinical outcome measures, including n = 403 individuals (239 carriers, 164 non-carriers) with Cambridge Behavioural Inventory-Revised scores during 2.8 ± 1.6 years, and n = 261 individuals (164 carriers, 97 non-carriers) with CDR Sum-of-Boxes scores during 2.0 ± 0.8 years. Regional cMD and CTh were entered into linear mixed-effects models incorporating age, sex and education as covariates; site, and individual nested within site were random intercepts. The results demonstrated that cMD is more sensitive than CTh to track early cortical injury, with elevated cMD first observed at CDR = 0 in C9orf72 carriers, followed by MAPT carriers (from CDR = 0.5 stage), and by GRN carriers (beginning at CDR ≥ 1). At all stages, cortical microstructural injury had stronger effect size and was more widespread than cortical thinning. In all mutation carrier types, cMD was more strongly associated than CTh with subsequent clinical progression. Cortical microstructure is a promising biomarker to identify at-risk individuals before atrophy and clinical progression, with utility in therapeutic trials.

Indexed as

Cerebral CortexFrontotemporal DementiaAdultAgedC9orf72 ProteinCross-Sectional StudiesDiffusion Magnetic Resonance ImagingDisease ProgressionFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMutationProgranulinsSeverity of Illness IndexC9orf72 ProteinC9orf72 protein, humanGRN protein, humanMAPT protein, humanProgranulinstau Proteins

Identifiers

PMID41068257
PMCPMC12602311

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.