Evidence map›Paper›PMID 41057914›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia.

Mahdie Soltaninejad, Mahsa Dadar, D Louis Collins, Reza Rajabli, Vikram Venkatraghavan, Arabella Bouzigues, Lucy L Russell, Phoebe H Foster, Eve Ferry-Bolder, John C van Swieten and 29 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 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. White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

39 authors.

Mahdie SoltaninejadMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
Mahsa DadarDouglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Québec, Canada.
D Louis CollinsMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
Reza RajabliMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
Vikram VenkatraghavanDepartment of Biomedical Engineering and Physics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Arabella BouziguesDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
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.
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.
Robert LaforceClinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, Québec, Canada.
Caroline GraffDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Bioclinicum, Karolinska Institutet, Solna, Sweden.
Daniela GalimbertiFondazione Ca' Granda, IRCCS Ospedale Policlinico, Milano, Italy.
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Alexandre de MendonçaFaculty of Medicine, University of Lisbon, Lisbon, Portugal.
Pietro TiraboschiFondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Isabel SantanaUniversity Hospital of Coimbra (HUC), Neurology Service, Faculty 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, LMU University Hospital, Munich, Germany.
Benedetta NacmiasDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Markus OttoDepartment of Neurology, University of Ulm, Ulm, Germany.
Maxime BertouxCentre Hospitalier Universitaire de Lille, Nord département, Lille, France.
Thibaud LebouvierCentre Hospitalier Universitaire de Lille, Nord département, Lille, France.
Chris R ButlerNuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Isabelle Le BerSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Hôpital Pitié, Paris, France.
Elizabeth FingerDepartment of Clinical Neurological Sciences, London Health Sciences Centre, University Hospital, University of Western Ontario, London, Ontario, Canada.
Maria Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Mario MasellisSunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
James B RoweDepartment of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, and MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Matthis SynofzikDepartment of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
Fermin MorenoCognitive Disorders Unit, Department of Neurology, Donostia Universitary Hospital, Donostia, Gipuzkoa, Spain.
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.
Yasser Iturria-MedinaMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
Simon DucharmeMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
GENFI Consortium

Funding

CIHR MOP-327387CIHR PJT-175242Fonds de Recherche du Québec - SantéMedical Research Council MC_UU_00030/14Medical Research Council MR/T033371/1NIHR Cambridge Biomedical Research Centre NIHR203312Wellcome TrustWellcome Trust 220258Weston Brain Institute
6 · The paper itself

Abstract

introductionIncreased white matter hyperintensities (WMHs) have been reported in genetic frontotemporal dementia (FTD) in small studies, but the sequence of WMH abnormalities relative to other biomarkers is unclear.

methodsUsing a large dataset (n = 763 GENFI2 participants), we measured WMHs and examined them across genetic FTD variants and stages. Cortical and subcortical volumes were parcellated, and serum neurofilament light chain (NfL) levels were measured. Biomarker progression was assessed with discriminative event-based and regression modeling.

resultsSymptomatic GRN carriers showed elevated WMHs, primarily in the frontal lobe, while no significant increase was observed in symptomatic C9orf72 or MAPT carriers. WMH abnormalities preceded NfL elevation, ventricular enlargement, and cortical atrophy. Longitudinally, baseline WMHs predicted subcortical changes, while subcortical volumes did not predict WMH changes, suggesting WMHs may precede neurodegeneration. DISCUSSION: WMHs are elevated in a subset of GRN-associated FTD. When present, they appear early and should be considered in disease progression models. HIGHLIGHTS: Elevated WMH volumes are found predominantly in symptomatic GRN. WMH accumulation is mostly observed in the frontal lobe. WMH abnormalities appear early in GRN-associated FTD, before NfL, atrophy, and ventriculomegaly. Longitudinally, WMH volumes can predict subcortical changes, but not vice versa. WMHs are key early markers in GRN-associated FTD and should be included in progression models.

Indexed as

Frontotemporal DementiaProgranulinsWhite MatterAgedAtrophyBiomarkersC9orf72 ProteinDisease ProgressionFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeurofilament Proteinstau ProteinsBiomarkersC9orf72 ProteinC9orf72 protein, humanGRN protein, humanMAPT protein, humanneurofilament protein LNeurofilament ProteinsProgranulinstau Proteinsbiomarker sequenceC9orf72dementiadisease progressionearly markerevent‐based modelingFTDGRNmagnetic resonance imagingMAPTneurodegenerationneurofilament light chainneuroimagingprogranulinwhite matter

Identifiers

PMID41057914
PMCPMC12504049

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.