Evidence map›Paper›PMID 40560468›Full record

ArticleJournal of neurology2025

Regional free-water diffusion is more strongly related to neuroinflammation than neurodegeneration.

Vishaal Sumra, Mohsen Hadian, Allison A Dilliott, Sali M K Farhan, Andrew R Frank, Anthony E Lang, Angela C Roberts, Angela Troyer, Stephen R Arnott, Connie Marras and 28 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Free water changes and their correlations with multimodal biomarkers in frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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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

38 authors.

Vishaal SumraInstitute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Cir Suite 2374, Toronto, ON, M5S 1A8, Canada. Vishaal.sumra@mail.utoronto.ca.ORCID http://orcid.org/0000-0002-4521-792X
Mohsen HadianKrembil Brain Institute, 135 Nassau St, Toronto, ON, M5T 1M8, Canada.
Allison A DilliottMontreal Neurological Institute and Hospital, 3801 Rue University, Montréal, QC, H3A 2B4, Canada.
Sali M K FarhanMontreal Neurological Institute and Hospital, 3801 Rue University, Montréal, QC, H3A 2B4, Canada.
Andrew R FrankUniversity of Ottawa, 75 Laurier Ave E, Ottawa, ON, K1N 6N5, Canada.
Anthony E LangTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Medical Sciences Building, 1 King's College Cir Suite 2374, Toronto, ON, M5S 1A8, Canada.
Angela C RobertsWestern University, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Angela TroyerBaycrest Health Sciences Centre, 3560 Bathurst St, Toronto, ON, M6A 2E1, Canada.
Stephen R ArnottBaycrest Hospital, 3560 Bathurst St, Toronto, ON, M6A 2E1, Canada.
Connie MarrasUniversity Health Network, 190 Elizabeth St, Toronto, ON, M5G 2C4, Canada.
David F Tang-WaiUniversity Health Network, 190 Elizabeth St, Toronto, ON, M5G 2C4, Canada.
Elizabeth FingerDepartment of Clinical Neurological Sciences, University of Western Ontario, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Medical Sciences Building, 1 King's College Cir Suite 2374, Toronto, ON, M5S 1A8, Canada.
Joseph B OrangeSchool of Communication Sciences and Disorders, University of Western Ontario, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Joel RamirezSunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
Lorne ZinmanFaculty of Medicine, University of Toronto, 27 King's College Cir, Toronto, ON, M5S 1A1, Canada.
Malcolm BinnsRotman Research Institute, 3560 Bathurst St, Toronto, ON, M6A 2E1, Canada.
Michael BorrieWestern University, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Morris FreedmanBaycrest Health Sciences Centre, 3560 Bathurst St, Toronto, ON, M6A 2E1, Canada.
Miracle OzzoudeTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Medical Sciences Building, 1 King's College Cir Suite 2374, Toronto, ON, M5S 1A8, Canada.
Robert BarthaRobarts Research Institute, Western University, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Richard H SwartzHurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
David MunozUnity Health Toronto, 61 Queen St E, Toronto, ON, M5C 2T2, Canada.
Mario MasellisSunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
Sandra E BlackSunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
Roger A DixonDepartment of Psychology Science, University of Alberta, 116 St & 85 Ave, Edmonton, AB, T6G 2R3, Canada.
Dar DowlatshahiUniversity of Ottawa, 75 Laurier Ave E, Ottawa, ON, K1N 6N5, Canada.
David GrimesOttawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON, K1Y 4E9, Canada.
Ayman HassanNorthern Ontario School of Medicine, 935 Ramsey Lake Rd, Sudbury, ON, P3E 2C6, Canada.
Robert A HegeleSchulich School of Medicine& Dentistry, Division of Geriatric Medicine, Western University, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Sanjeev KumarCentre for Addiction and Mental Health, 1000 Queen St W, Toronto, ON, M6J 1H4, Canada.
Stephen PasternakRobarts Research Institute, Western University, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Bruce PollockSchool of Communication Sciences and Disorders, University of Western Ontario, 1151 Richmond St, London, ON, N6A 3K7, Canada.
Tarek RajjiCentre for Addiction and Mental Health, 1000 Queen St W, Toronto, ON, M6J 1H4, Canada.
Demetrios SahlasMcMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada.
Gustavo SaposnikUnity Health Toronto, 61 Queen St E, Toronto, ON, M5C 2T2, Canada.
Maria Carmela TartagliaInstitute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Cir Suite 2374, Toronto, ON, M5S 1A8, Canada.
ONDRI Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionRecent research has suggested that neuroinflammation may be important in the pathogenesis of neurodegenerative diseases. Free-water diffusion (FWD) has been proposed as a non-invasive neuroimaging-based biomarker for neuroinflammation.

methodsFree-water maps were generated using diffusion MRI data in 367 patients from the Ontario Neurodegenerative Disease Research Initiative (108 Alzheimer's Disease/Mild Cognitive Impairment, 42 Frontotemporal Dementia, 37 Amyotrophic Lateral Sclerosis, 123 Parkinson's Disease, and 58 vascular disease-related Cognitive Impairment). The ability of FWD to predict neuroinflammation and neurodegeneration from biofluids was estimated using plasma glial fibrillary-associated protein (GFAP) and neurofilament light chain (NfL), respectively.

resultsRecursive Feature Elimination (RFE) performed the strongest out of all feature selection algorithms used and revealed regional specificity for areas that are the most important features for predicting GFAP over NfL concentration. Deep learning models using selected features and demographic information revealed better prediction of GFAP over NfL. DISCUSSION: Based on feature selection and deep learning methods, FWD was found to be more strongly related to GFAP concentration (measure of astrogliosis) over NfL (measure of neuro-axonal damage), across neurodegenerative disease groups, in terms of predictive performance. Non-invasive markers of neurodegeneration such as MRI structural imaging that can reveal neurodegeneration already exist, while non-invasive markers of neuroinflammation are not available. Our results support the use of FWD as a non-invasive neuroimaging-based biomarker for neuroinflammation.

Indexed as

Diffusion Magnetic Resonance ImagingNeurodegenerative DiseasesNeuroinflammatory DiseasesAgedAged, 80 and overBiomarkersCognitive DysfunctionFemaleGlial Fibrillary Acidic ProteinHumansMaleMiddle AgedNeurofilament ProteinsBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsBiomarkersDiffusion MRIFreewaterNeurodegenerationNeurodegenerative diseaseQuantitative MRI

Identifiers

PMID40560468

What Socratic holds

Textmetadata
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 Socratic graph.