Garcia Castro, Jesús
Mayo Clinic
Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Citations 2
Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia
Castro, J. García , Rubio‐Guerra, Sara , Casaletto, Kaitlin B. , Selma, Judit , Memel, Molly , Vaqué‐Alcázar, Lídia , Morcillo‐Nieto, Alejandra O. , Arriola‐Infante, José Enrique , Dols‐Icardo, Oriol , Bejanin, Alexandre , Belbin, Olivia , Carmona‐Iragui, María , Barroeta, Isabel , Santos‐Santos, Miguel , Saudinós, María Belen Sánchez, Sala, Isabel , Heuer, Hilary W. , Forsberg, Leah K. , Kantarci, Kejal, Staffaroni, Adam M. , Rankin, Katherine P. , Boxer, Adam L. , Rosen, Howard J. , Lleó, Alberto, Illán‐Gala, Ignacio , Kantarci, Kejal , Belbin, Olivia , Garcia Castro, Jesús , Illán-Gala, Ignacio , Bejanin, Alexandre , Kantarci, Kejal , Selma‐González, Judit , Fortea, Juan , Alcolea, Daniel , Sánchez‐Saudinós, María Belén , Tartaglia, Maria Carmela , Boeve, Bradley F. , Lleó, Alberto
Alzheimer's & Dementia | April 25, 2025 | Volume: 21 | Issue: 4 | Pages: No page available
AbstractINTRODUCTIONSelf‐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.
Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia
Memel, Molly , Staffaroni, Adam M. , Ilan‐Gala, Ignacio, Castro, J. García , Kornak, John , Tartaglia, Carmela M., Saloner, Rowan, Cadwallader, Claire J. , Chen, Coty , Gorno‐Tempini, Maria Luisa , Mandelli, Malu, Apostolova, Liana , Graff-Radford, N. R., Pressman, Peter , Miyagawa, Toji , Mackenzie, Ian R. , Darby, R. Ryan , Petrucelli, Len, Gendron, Tania, Heuer, Hilary W. , Forseberg, Leah K., Brushaber, Nellie, Domoto‐Reilly, Kimiko , Ghoshal, Nupur , Pascual, Belén , Lee, Suzee, Ramos, Eliana Marisa , Rademakers, Rosa , Rascovsky, Katya, Masdeu, Joseph C. , Boxer, Adam L., Rosen, Howard J. , Casaletto, Kaitlin B. , Illán‐Gala, Ignacio , Graff-Radford, Neil, Boeve, Brad F, Pascual, Belen , Domoto-Reilly, Kimiko , Garcia Castro, Jesús , Illán-Gala, Ignacio , Saloner, Rowan , VandeBunte, Anna M. , Paolillo, Emily W. , Litvan, Irene , Bayram, Ece , Goldman, Jill , Appleby, Brian S. , Gendron, Tania F. , Rojas, Julio C. , Boeve, Bradley F. , Lapid, Maria I. , Ramanan, Vijay K. , Pantelyat, Alexander , Masdeu, Joseph C , Snyder, Allison , Boxer, Adam L.
Alzheimer's & Dementia | April 25, 2025 | Volume: 21 | Issue: 4 | Pages: No page available
Abstract 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.