Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia
Garcia Castro, Jesús (Institut de Recerca Sant Pau)
Rubio-Guerra, Sara (Institut de Recerca Sant Pau)
Casaletto, Kaitlin B. (University of California)
Selma González, Judit (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Memel, M. (Ray Dolby Brain Health Center)
Vaqué-Alcázar, Lídia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Morcillo-Nieto, Alejandra (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Arriola Infante, José Enrique (Institut de Recerca Sant Pau)
Dols Icardo, Oriol (Institut de Recerca Sant Pau)
Bejanin, Alexandre (Institut de Recerca Sant Pau)
Belbin, Olivia (Institut de Recerca Sant Pau)
Fortea, Juan (Institut de Recerca Sant Pau)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Carmona Iragui, María (Institut de Recerca Sant Pau)
Barroeta, Isabel (Institut de Recerca Sant Pau)
Santos-Santos, Miguel (Institut de Recerca Sant Pau)
Sánchez Saudinós, María Belen (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Sala Matavera, Isabel (Institut de Recerca Sant Pau)
Heuer, H.W. (University of California)
Forsberg, L.K. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Kantarci, K. (Mayo Clinic)
Staffaroni, A.M. (University of California)
Tartaglia, C. (University of Toronto)
Rankin, K.P. (University of California)
Boeve, B. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Boxer, A. (University of California)
Rosen, H.J. (University of California)
Lleó, Alberto (Institut de Recerca Sant Pau)
Illán-Gala, Ignacio (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Date:	2025
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI21/00791 Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI23/01786 Instituto de Salud Carlos III PI22/00307 Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI20/01330 Instituto de Salud Carlos III PI21/01395
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cognitive reserve ; Diagnosis ; Frontotemporal dementia ; Magnetic resonance imaging ; Neuroimaging ; Progression ; Resilience ; Survival
Published in:	Alzheimer's & dementia, Vol. 21 Núm. 4 (april 2025) , p. e70070, ISSN 1552-5279

DOI: 10.1002/alz.70070
PMID: 40277045

15 p, 1.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles