Jesús Garcia Castro, Sara Rubio-Guerra, Kaitlin B. Casaletto, Judit Selma González, Molly Memel, Lídia Vaqué-Alcázar, Alejandra Morcillo-Nieto, José Arriola-Infante, Oriol Dols-Icardo, Alexandre Bejanin, Olivia Belbin, Juan Fortea, Daniel Alcolea, Maria Carmona-Iragui, Isabel Barroeta, Miguel Santos-Santos, María Belen Sánchez Saudinós, Isabel Sala Matavera, Hilary W. Heuer, Leah K. Forsberg, Kejal Kantarci, Adam M. Staffaroni, Carmela Tartaglia, Katherine P. Rankin, Brad Boeve, Adam Boxer, Howard J. Rosen, Alberto Lleó, Ignacio Illán-Gala, for the ALLFTD Consortium
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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.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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