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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\u2010effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Symptomatic females with genetic FTD had lower frontal cortical thickness than males, and the <jats:italic>C9orf72<\/jats:italic> subgroup showed lower\u2010than\u2010expected frontal cortical thickness for a given level of executive functioning. Differences in cognitive reserve between sexes peaked near symptom onset but diminished thereafter.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Females with genetic FTD showed higher cognitive reserve than males, suggesting that self\u2010reported sex modulates resilience to frontotemporal neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Females with genetic FTD showed higher cognitive reserve than males.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Those differences were particularly pronounced in the <jats:italic>C9orf72<\/jats:italic> and <jats:italic>GRN<\/jats:italic> subgroups.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The higher cognitive reserve in females declined as the disease progressed.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70070","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T07:00:23Z","timestamp":1745564423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1503-4775","authenticated-orcid":false,"given":"Jes\u00fas","family":"Garcia Castro","sequence":"first","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rubio\u2010Guerra","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin B.","family":"Casaletto","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, Memory and Aging Center University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Selma Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Memel","sequence":"additional","affiliation":[{"name":"Ray Dolby Brain Health Center  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Vaqu\u00e9\u2010Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Morcillo\u2010Nieto","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Arriola\u2010Infante","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid 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Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Belbin","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Alcolea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carmona\u2010Iragui","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Barroeta","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Santos\u2010Santos","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Belen","family":"S\u00e1nchez Saudin\u00f3s","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Sala Matavera","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Departament de Medicina Universitat Aut\u00f2noma de Barcelona  Cerdanyola del Vall\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary W.","family":"Heuer","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, Memory and Aging Center University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah K.","family":"Forsberg","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejal","family":"Kantarci","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Staffaroni","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, Memory and Aging Center University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine P.","family":"Rankin","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, Memory and Aging Center University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota 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