Evidence map›Paper›PMID 38961774›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

Daniela Andriuta, Julie Ottoy, Myuri Ruthirakuhan, Ginelle Feliciano, Allison A Dilliott, Robert A Hegele, Fuqiang Gao, Paula M McLaughlin, Jennifer S Rabin, Madeline Wood Alexander and 31 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Human Neurotoxicity of Trichloroethylene: A Biomarker Approach.Journal of applied toxicology : JAT · 2026
    Article
  3. Article
  4. Article
  5. Intestinal inflammation induces glymphatic remodeling, priming early neurodegenerative signals in male mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Plasma NfL and GFAP for predicting VCI and related brain changes in community and clinical cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  10. Article
  11. Article
  12. Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  13. Review
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

41 authors.

Daniela AndriutaDepartment of Neurology, Amiens University Medical Center, Amiens, France.ORCID 0000-0002-1191-7178
Julie OttoyDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Myuri RuthirakuhanDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Ginelle FelicianoDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Allison A DilliottDepartment of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec, Canada.
Robert A HegeleRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Toronto, Ontario, Canada.
Fuqiang GaoDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Paula M McLaughlinNova Scotia Health, Halifax, Nova Scotia, Canada.
Jennifer S RabinDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Madeline Wood AlexanderDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Christopher J M ScottDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Vanessa YhapDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Courtney BerezukDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Miracle OzzoudeDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Walter SwardfagerDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Julia ZebarthDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
M Carmela TartagliaDivision of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
David F Tang-WaiDivision of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Leanne CasaubonDivision of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Sanjeev KumarDepartment of Psychiatry, Adult Neurodevelopment and Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Dar DowlatshahiUniversity of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Jennifer MandziaRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Toronto, Ontario, Canada.
Demetrios SahlasDivision of Neurology, Department of Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Gustavo SaposnikLi Ka Shing Knowledge Institute, and Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Corinne E FischerLi Ka Shing Knowledge Institute, and Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Michael BorrieRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Toronto, Ontario, Canada.
Ayman HassanDivision of Neurology, Department of Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Malcolm A BinnsRotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
Morris FreedmanRotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
Howard ChertkowDivision of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Elizabeth FingerRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Toronto, Ontario, Canada.
Andrew FrankUniversity of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Robert BarthaRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Toronto, Ontario, Canada.
Sean SymonsDepartment of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Richard H SwartzDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Mario MasellisDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Sandra E BlackDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Joel RamirezDr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
ONDRI Investigators

Funding

AD Strategic FundAlzheimer Drug Discovery Foundation (ADDF) #201809-2016862Alzheimer's Association #ADSF-21-831376-CAlzheimer's Association #ADSF-21-831377-CAlzheimer's Association #ADSF-21-831381-CAlzheimer Society of LondonBluefield Project, Cure Alzheimer's FundBrain and Behavior FoundationBrightFocus FoundationCanadian Consortium on Neurodegeneration in AgingCanadian Institute of Health ResearchCentre for Addiction and Mental HealthCentre for Ageing and Brain Health InnovationDr. Sandra Black Centre for Brain Resilience and RecoveryErling-Persson Family FoundationEuropean Union Joint Programme-Neurodegenerative Disease Research JPND2021-00694European Union's Horizon 2020 research and innovation programmeEuropean Union's Horizon Europe research and innovation programme 101053962Foundation Leducq Transatlantic Network of Excellence for their support of PVS-related studiesLinda C. Campbell FoundationMiddlesex Doctoral Graduate Research ScholarshipNational Institute for Health and Care Research University College London Hospitals Biomedical Research CentreNational Institute on AgeingOlav Thon FoundationStiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden #FO2022-0270Swedish Research Council #2019-02397Swedish Research Council #2022-01018Swedish Research Council #2023-00356Swedish State Support for Clinical Research #ALFGBG-71320UK Dementia Research Institute at UCL UKDRI-1003Weston UK Brain Institute,
6 · The paper itself

Abstract

introductionWe investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.

methodsA mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.

resultsPVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Indexed as

BiomarkersExecutive FunctionGlial Fibrillary Acidic ProteinGlymphatic SystemMagnetic Resonance ImagingNeurodegenerative DiseasesWhite MatterAgedAlzheimer DiseaseBrainCerebrovascular DisordersCognitive DysfunctionCohort StudiesFemaleFrontotemporal DementiaHumansBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteincerebrovascular diseasesexecutive functionneurodegenerative diseasesperivascular spacesplasma glial fibrillary acidic proteinwhite matter hyperintensities

Identifiers

PMID38961774
PMCPMC11350014

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.