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Record W4409812731 · doi:10.1002/alz.70070

Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia

2025· article· en· W4409812731 on OpenAlexafffund
J. García Castro, Sara Rubio‐Guerra, Kaitlin B. Casaletto, Judit Selma, Molly Memel, Lídia Vaqué‐Alcázar, Alejandra O. Morcillo‐Nieto, José Enrique Arriola‐Infante, Oriol Dols‐Icardo, Alexandre Bejanin, Olivia Belbin, Juan Fortea, Daniel Alcolea, María Carmona‐Iragui, Isabel Barroeta, Miguel Santos‐Santos, María Belen Sánchez Saudinós, Isabel Sala, Hilary W. Heuer, Leah K. Forsberg, Kejal Kantarci, Adam M. Staffaroni, Maria Carmela Tartaglia, Katherine P. Rankin, Bradley F. Boeve, Adam L. Boxer, Howard J. Rosen, Alberto Lleó, Ignacio Illán‐Gala

Bibliographic record

VenueAlzheimer s & Dementia · 2025
Typearticle
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersNational Center for Advancing Translational SciencesUniversity of California, San FranciscoHorizon 2020 Framework ProgrammeCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasNational Institutes of HealthGeneralitat de CatalunyaEuropean Regional Development FundEuropean CommissionInstituto de Salud Carlos IIIFundación Tatiana Pérez de Guzmán el BuenoAlzheimer SocietyGlobal Brain Health InstituteNational Institute on AgingAlzheimer's Association
KeywordsFrontotemporal dementiaCognitive reserveNeuropsychologyC9orf72PsychologyCognitionExecutive functionsEffects of sleep deprivation on cognitive performanceCognitive declineAudiologyDementiaClinical psychologyNeuroscienceMedicineDiseaseInternal medicineCognitive impairment

Abstract

fetched live from OpenAlex

INTRODUCTION: Self-reported sex influences brain resilience, but its role in genetic frontotemporal dementia (FTD) remains unclear. METHODS: We analyzed 394 genetic-FTD patients and 279 controls from the ALLFTD consortium, assessing annual neuropsychological performance and MRI-based cortical thickness. Clinical characteristics and cortical thickness were compared between sexes. We used the residuals of linear regression models, which predict each participant's cognitive and behavioral performance levels relative to cortical thickness, as a proxy for reserve. We then modeled sex differences in longitudinal trajectories with linear mixed-effects models. RESULTS: Symptomatic females with genetic FTD had lower frontal cortical thickness than males, and the C9orf72 subgroup showed lower-than-expected frontal cortical thickness for a given level of executive functioning. Differences in cognitive reserve between sexes peaked near symptom onset but diminished thereafter. DISCUSSION: Females with genetic FTD showed higher cognitive reserve than males, suggesting that self-reported sex modulates resilience to frontotemporal neurodegeneration. HIGHLIGHTS: Females with genetic FTD showed higher cognitive reserve than males. Those differences were particularly pronounced in the C9orf72 and GRN subgroups. The higher cognitive reserve in females declined as the disease progressed.

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)0.002
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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.059
GPT teacher head0.338
Teacher spread0.279 · 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

Citations5
Published2025
Admission routes2
Has abstractyes

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