José Contador*, Agnès Pérez-Millan*, Nuria Guillen, Jordi Sarto, Adrià Tort-Merino, Mircea Balasa, Neus Falgàs, Magdalena Castellví, Sergi Borrego-Écija, Jordi Juncà-Parella, Beatriz Bosch, Guadalupe Fernández-Villullas, Oscar Ramos-Campoy, Anna Antonell, Nuria Bargalló, Raquel Sanchez-Valle, Roser Sala Llonch, Albert Lladó (* equivalent contribution). European Journal of Neurology.
ABSTRACT
INTRODUCTION: Sex is believed to drive heterogeneity in Alzheimer’s disease (AD), although evidence in early-onset AD (<65 years, EOAD) is scarce.
METHODS: We included 62 EOAD patients and 44 healthy controls (HC) with cerebrospinal fluid (CSF) AD’s core biomarkers and neurofilament light chain levels, neuropsychological assessment, and 3T-MRI. We measured cortical thickness (CTh) and hippocampal subfield volumes (HpS) using Freesurfer. Adjusted linear models were used to analyze sex-differences and the relationship between atrophy and cognition.
RESULTS:Compared to same-sex HC, female-EOAD showed greater cognitive impairment and broader atrophy burden than male-EOAD. In a direct female-EOAD and male-EOAD comparison, there were slight differences in temporal CTh, with no differences in cognition or HpS. CSF tau levels were higher in female-EOAD than in male-EOAD. Greater atrophy was associated with worse cognition in female-EOAD.
CONCLUSIONS: At diagnosis, there are sex-differences in the pattern of cognitive impairment, atrophy burden and CSF tau in EOAD, suggesting there is an influence of sex on pathology spreading and susceptibility to the disease in EOAD.