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Record W4400332537 · doi:10.1002/alz.14081

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

2024· article· en· W4400332537 on OpenAlexafffundabout
Daniela Andriuta, Julie Ottoy, Myuri Ruthirakuhan, Ginelle Feliciano, Allison A. Dilliott, Robert A. Hegele, Fuqiang Gao, Paula McLaughlin, Jennifer S. Rabin, Madeline Wood Alexander, Christopher J.M. Scott, Vanessa Yhap, Courtney Berezuk, Miracle Ozzoude, Walter Swardfager, Julia Zebarth, Maria Carmela Tartaglia, Ekaterina Rogaeva, David F. Tang‐Wai, Leanne K. Casaubon, Sanjeev Kumar, Dar Dowlatshahi, Jennifer Mandzia, Demetrios J. Sahlas, Gustavo Saposnik, Corinne E. Fischer, Michael Borrie, Ayman Hassan, Malcolm A. Binns, Morris Freedman, Howard Chertkow, Elizabeth Finger, Andrew Frank, Robert Bartha, Sean Symons, Henrik Zetterberg, Richard H. Swartz, Mario Masellis, Sandra E. Black, Joel Ramirez

Bibliographic record

VenueAlzheimer s & Dementia · 2024
Typearticle
Languageen
FieldNeuroscience
TopicCerebrospinal fluid and hydrocephalus
Canadian institutionsOttawa HospitalBruyèreThe Scarborough HospitalPublic Health OntarioBaycrest HospitalMcMaster UniversityHamilton Health SciencesCentre for Addiction and Mental HealthToronto Western HospitalThunder Bay Regional Research InstituteSunnybrook HospitalWestern UniversityNova Scotia Health AuthorityUniversity of OttawaMcGill UniversityHealth Sciences CentreOccupational Cancer Research CentreUniversity Health NetworkUniversity of TorontoMontreal Neurological Institute and HospitalOntario Brain InstituteToronto Rehabilitation InstituteSt. Michael's HospitalSunnybrook Health Science Centre
FundersCanadian Institutes of Health ResearchHORIZON EUROPE Framework ProgrammeOlav Thon StiftelsenDepartment of Psychiatry, University of TorontoTemerty Family FoundationUK Dementia Research InstituteFondation Brain CanadaFamiljen Erling-Perssons StiftelseEuropean CommissionHjärnfondenLinda C. Campbell FoundationQueen's UniversityUniversity of TorontoFaculty of Health Sciences, Queen's UniversityUniversity College LondonNational Institute for Health and Care ResearchLondon Health Sciences FoundationCentre for Addiction and Mental Health FoundationConsortium canadien en neurodégénérescence associée au vieillissementGovernment of OntarioEU Joint Programme – Neurodegenerative Disease ResearchAlzheimer's AssociationStiftelsen för Gamla TjänarinnorCentre for Addiction and Mental HealthUniversity of OttawaVetenskapsrådetCure Alzheimer's FundMcMaster UniversityAlzheimer SocietyBrightFocus FoundationAlzheimer's Drug Discovery Foundation
KeywordsNeurodegenerationGlial fibrillary acidic proteinHyperintensityFrontotemporal dementiaBiomarkerMedicineDementiaWhite matterExecutive dysfunctionNeurosciencePathologyDiseasePerivascular spaceNeuroimagingPsychologyInternal medicineMagnetic resonance imagingCognitionBiologyNeuropsychologyRadiologyImmunohistochemistry

Abstract

fetched live from OpenAlex

INTRODUCTION: We 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. METHODS: A 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. RESULTS: PVS 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.016
Threshold uncertainty score0.032

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.258
Teacher spread0.233 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2024
Admission routes3
Has abstractyes

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