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Record W4409812814 · doi:10.1002/alz.14630

Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia

2025· article· en· W4409812814 on OpenAlexaff
Molly Memel, Adam M. Staffaroni, Ignacio Ilan‐Gala, J. García Castro, John Kornak, Carmela M. Tartaglia, Rowan Saloner, Anna M. VandeBunte, Emily W. Paolillo, Claire J. Cadwallader, Coty Chen, Maria Luisa Gorno‐Tempini, Malu Mandelli, Liana Apostolova, N. R. Graff-Radford, Irene Litvan, Ece Bayram, Peter Pressman, Toji Miyagawa, Ian R. Mackenzie, Jill Goldman, R. Ryan Darby, Brian S. Appleby, Len Petrucelli, Tania Gendron, Hilary W. Heuer, Leah K. Forseberg, Julio C. Rojas, Bradley F. Boeve, Nellie Brushaber, Kimiko Domoto‐Reilly, Nupur Ghoshal, Maria I. Lapid, Belén Pascual, Suzee Lee, Eliana Marisa Ramos, Vijay K. Ramanan, Rosa Rademakers, Katya Rascovsky, Alexander Pantelyat, Joseph C. Masdeu, Allison Snyder, Adam L. Boxer, Howard J. Rosen, Kaitlin B. Casaletto

Bibliographic record

VenueAlzheimer s & Dementia · 2025
Typearticle
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsUniversity of British ColumbiaUniversity of Toronto
FundersNational Institute on AgingUniversity of California, San FranciscoNational Institutes of HealthH. Lundbeck A/SNational Institute of Neurological Disorders and StrokeAlzheimer's AssociationAbbVieRocheParkinson's FoundationNational Center for Advancing Translational SciencesMichael J. Fox Foundation for Parkinson's Research
KeywordsFrontotemporal dementiaAsymptomaticDiseasePathologicalDementiaMedicineInternal medicinePsychologyClinical psychology

Abstract

fetched live from OpenAlex

INTRODUCTION: Sex differences are apparent in neurodegenerative diseases but have not been comprehensively characterized in frontotemporal dementia (FTD). METHODS: Participants included 337 adults with autosomal dominant FTD enrolled in the ALLFTD Consortium. Clinical assessments and plasma were collected annually for up to 6 years. Linear mixed-effects models investigated how sex and disease stage are associated with longitudinal trajectories of cognition, function, and neurofilament light chain (NfL). RESULTS: While sex differences were not apparent at asymptomatic stages, females showed more rapid declines across all outcomes in symptomatic stages compared to males. In asymptomatic participants, the association between baseline NfL and clinical trajectories was weaker in females versus males, a difference that was not present in symptomatic participants. DISCUSSION: In genetic FTD, females show cognitive resilience in early disease stages followed by steeper clinical declines later in the disease. Baseline NfL may be a less sensitive prognostic tool for clinical progression in females with FTD-causing mutations. HIGHLIGHTS: Females with genetic FTD exhibit overall steeper increases in plasma neurofilament light chain (NfL) than males. Females with genetic FTD outperform NfL levels in asymptomatic stages compared to males. Once symptomatic, females with genetic FTD decline more rapidly than males. Plasma NfL is a stronger prognostic marker in asymptomatic males than females.

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 score0.003
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.076
GPT teacher head0.371
Teacher spread0.294 · 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

Citations12
Published2025
Admission routes1
Has abstractyes

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