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Record W4392809360 · doi:10.1038/s41467-024-46603-2

A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings

2024· article· en· W4392809360 on OpenAlexafffund
Wagner S. Brum, Nicholas Cullen, Joseph Therriault, Shorena Janelidze, Nesrine Rahmouni, Jenna Stevenson, Stijn Servaes, Andréa Lessa Benedet, Eduardo R. Zimmer, Erik Stomrud, Sebastian Palmqvist, Henrik Zetterberg, Giovanni B. Frisoni, Nicholas J. Ashton, Kaj Blennow, Niklas Mattsson, Pedro Rosa‐Neto, Oskar Hansson

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersFonds de Recherche du Québec - SantéNational Institutes of HealthKonung Gustaf V:s och Drottning Victorias FrimurarestiftelseParkinsonfondenHjärnfondenSkånes universitetssjukhusCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEU Joint Programme – Neurodegenerative Disease ResearchEuropean CommissionKnut och Alice Wallenbergs StiftelseFondation Brain CanadaNational Institute on AgingConsortium canadien en neurodégénérescence associée au vieillissementAlzheimer's AssociationVetenskapsrådetCure Alzheimer's FundAustralian GovernmentLunds UniversitetStiftelsen för Gamla TjänarinnorCanadian Institutes of Health ResearchAlzheimerfondenWeston Brain InstituteAlzheimer's Drug Discovery Foundation
KeywordsMedicineBiomarkerDementiaMemory clinicInternal medicinePositron emission tomographyCognitive declineOncologyReferralNuclear medicineDiseaseFamily medicine

Abstract

fetched live from OpenAlex

Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer's disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; "saved scans") and the tau-PET-positivity rate among participants above the cutoffs (who would undergo tau-PET; "positive predictive value"). Generally, plasma pTau217 performed best. At the 95% sensitivity cutoff in both cohorts, pTau217 resulted in avoiding nearly half tau-PET scans, with a tau-PET-positivity rate among those who would be referred for a scan around 70%. And although tau-PET was strongly associated with subsequent cognitive decline, in BioFINDER-2 it predicted cognitive decline only among individuals above the referral cutoff on plasma pTau217, supporting that this workflow could reduce prognostically uninformative tau-PET scans. In conclusion, plasma pTau217 may guide selection of patients for tau-PET, when accurate prognostic information is of clinical value.

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)0.012
metaresearch head score (Gemma)0.023
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: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.014
Threshold uncertainty score0.061

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0120.023
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.002
Science and technology studies0.0010.001
Scholarly communication0.0050.002
Open science0.0020.002
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0080.008

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 head0.049
GPT teacher head0.408
Teacher spread0.359 · 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

Citations30
Published2024
Admission routes2
Has abstractyes

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