Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia.
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Memel Molly, Staffaroni Adam M, Ilan-Gala Ignacio, Castro Jesús Garcia, Kornak John, Tartaglia Carmela M, Saloner Rowan, VandeBunte Anna M, Paolillo Emily W, Cadwallader Claire J, Chen Coty, Gorno-Tempini Maria Luisa, Mandelli Malu, Apostolova Liana, Graff-Radford Neil, Litvan Irene, Bayram Ece, Pressman Peter S, Miyagawa Toji, Mackenzie Ian, Goldman Jill, Darby Richard R, Appleby Brian S, Petrucelli Len, Gendron Tania, Heuer Hilary W, Forseberg Leah K, Rojas Julio C, Boeve Brad F, Brushaber Nellie, Domoto-Reilly Kimiko, Ghoshal Nupur, Lapid Maria, Pascual Belen, Lee Suzee, Ramos Eliana Marisa, Ramanan Vijay, Rademakers Rosa, Rascovsky Katya, Pantelyat Alex, Masdeu Joseph C, Snyder Allison, Boxer Adam L, Rosen Howard J, Casaletto Kaitlin, ALLFTD Consortium
Аннотация
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.