Sex differences in early-onset Alzheimer's disease

European journal of neurology

Eur J Neurol. 2022 Dec;29(12):3623-3632. doi: 10.1111/ene.15531. Epub 2022 Sep 9.


BACKGROUND AND PURPOSE: Sex is believed to drive heterogeneity in Alzheimer's disease (AD), although evidence in early-onset AD (EOAD; <65 years) is scarce.

METHODS: We included 62 EOAD patients and 44 healthy controls (HCs) with core AD cerebrospinal fluid (CSF) biomarkers, neurofilament light chain levels, neuropsychological assessment, and 3-T magnetic resonance imaging. 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 HCs, female EOAD subjects showed greater cognitive impairment and broader atrophy burden than male EOAD subjects. In a direct female-EOAD versus 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 subjects. Greater atrophy was associated with worse cognition in female EOAD subjects.

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.

PMID:36005384 | DOI:10.1111/ene.15531


José Contador
Agnès Pérez-Millan
Nuria Guillén
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