Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia
Por:
Castro, JG, Rubio-Guerra, S, Casaletto, KB, González, JS, Memel, M, Vaqué-Alcázar, L, Morcillo-Nieto, A, Arriola-Infante, J, Dols-Icardo, O, Bejanin, A, Belbin, O, Fortea, J, Alcolea, D, Carmona-Iragui, M, Barroeta, I, Santos-Santos, M, Saudinós, MBS, Matavera, IS, Heuer, HW, Forsberg, LK, Kantarci, K, Staffaroni, AM, Tartaglia, C, Rankin, KP, Boeve, B, Boxer, A, Rosen, HJ, Lleó, A, Illán-Gala, I
Publicada:
1 abr 2025
Resumen:
INTRODUCTIONSelf-reported sex influences brain resilience, but its role in genetic frontotemporal dementia (FTD) remains unclear.METHODSWe 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.RESULTSSymptomatic 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.DISCUSSIONFemales 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.
Filiaciones:
Castro, JG:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Rubio-Guerra, S:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Casaletto, KB:
Univ Calif San Francisco, Weill Inst Neurosci, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA
González, JS:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Memel, M:
Ray Dolby Brain Hlth Ctr, San Francisco, CA USA
Vaqué-Alcázar, L:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Morcillo-Nieto, A:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Arriola-Infante, J:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Dols-Icardo, O:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Bejanin, A:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Belbin, O:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Fortea, J:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Alcolea, D:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Carmona-Iragui, M:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Barroeta, I:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Santos-Santos, M:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Saudinós, MBS:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Matavera, IS:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Heuer, HW:
Univ Calif San Francisco, Weill Inst Neurosci, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA
Forsberg, LK:
Mayo Clin, Dept Neurol, Rochester, MN USA
Kantarci, K:
Mayo Clin, Dept Radiol, Rochester, MN USA
Staffaroni, AM:
Univ Calif San Francisco, Weill Inst Neurosci, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA
Tartaglia, C:
Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada
Rankin, KP:
Univ Calif San Francisco, Weill Inst Neurosci, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA
Boeve, B:
Mayo Clin, Dept Neurol, Rochester, MN USA
Boxer, A:
Univ Calif San Francisco, Weill Inst Neurosci, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA
Rosen, HJ:
Univ Calif San Francisco, Weill Inst Neurosci, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA
Lleó, A:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Illán-Gala, I:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
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