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Record W4390193359 · doi:10.1002/alz.076588

Examining longitudinal changes of disease severity scores in familial forms of frontotemporal dementia within the GENFI cohort

2023· article· en· W4390193359 on OpenAlexaff
Phoebe H. Foster, Eve Ferry‐Bolder, Georgia Peakman, Arabella Bouzigues, Caroline Greaves, Rhian S. Convery, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Fermín Moreno, Raquel Sánchez‐Valle, Robert Laforce, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Barbara Borroni, Elizabeth Finger, Matthis Synofzik, Daniela Galimberti, Rik Vandenberghe, Alexandre de Mendonça, Christopher Butler, Alexander Gerhard, Simon Ducharme, Isabelle Le Ber, Pietro Tiraboschi, Isabel Santana, Florence Pasquier, Johannes Levin, Markus Otto, Sandro Sorbi, Jonathan D. Rohrer, Lucy L. Russell

Bibliographic record

VenueAlzheimer s & Dementia · 2023
Typearticle
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsMcGill UniversityWestern UniversityOccupational Cancer Research CentreSunnybrook HospitalMontreal Neurological Institute and HospitalUniversity of TorontoSunnybrook Health Science CentreUniversité Laval
Fundersnot available
KeywordsC9orf72Frontotemporal dementiaInternal medicineAsymptomaticMedicineAsymptomatic carrierMutationCohortDementiaTrinucleotide repeat expansionOncologyDiseaseAlleleGeneticsBiologyGene

Abstract

fetched live from OpenAlex

Abstract Background The CDR®+NACC FTLD Sum of Boxes (SB) score is a well‐established measure of disease severity in frontotemporal dementia (FTD), however, few studies have assessed longitudinal changes in score within familial forms of FTD. Method 343 participants from the Genetic FTD Initiative (77 mutation‐negative controls, 109 C9orf72 expansion carriers, 105 GRN mutation carriers, and 52 MAPT mutation carriers), with available scores on the CDR®+NACC FTLD‐SB and the FTD Rating Scale (FRS) at baseline and follow‐up, were examined. Using the baseline FRS percentage scores, mutation carriers were stratified into four groups: asymptomatic/very mild (100‐97%), mild (96‐80%), moderate (79‐41%), and severe (40‐0%). Linear regression models with bootstrapping were used to assess annualised change in CDR®+NACC FTLD‐SB scores across genetic groups between participants' first and follow‐up visit. Result C9orf72 and GRN mutation carriers in the moderate and severe groups, as well as mild GRN carriers, showed significantly greater change than controls (p < 0.050). No significant differences in change scores were observed between MAPT mutation carriers and controls. Comparisons within genetic groups revealed that both the moderate and severe GRN and C9orf72 expansion carriers showed larger annualised change relative to their asymptomatic/very mild counterparts (p < 0.001 and p = 0.037; p = 0.028 and p < 0.001, respectively). The moderate GRN and severe C9orf72 groups also demonstrated greater annualised score changes than their respective mild counterparts (p < .001; p = 0.001). For MAPT mutation carriers, no significant changes were observed. Between genetic group comparisons revealed significant change score differences between the moderate individuals, with GRN mutation carriers showing a greater change than the C9orf72 and MAPT groups (both p < 0.001), and the C9orf72 group showing a larger annualised change than the MAPT mutation carriers (p = 0.041). Conclusion The CDR®+NACC FTLD‐SB detects significant changes in disease severity from baseline to a first follow‐up visit in familial forms of FTD, with GRN mutation carriers showing the greatest annualised change.

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)0.002
metaresearch head score (Gemma)0.002
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 score0.036
Threshold uncertainty score0.072

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.084
GPT teacher head0.317
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

Citations1
Published2023
Admission routes1
Has abstractyes

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