Journal
EUROPEAN JOURNAL OF NEUROLOGY
Volume 29, Issue 12, Pages 3623-3632Publisher
WILEY
DOI: 10.1111/ene.15531
Keywords
Alzheimer's disease; atrophy; biomarkers; cerebrospinal fluid; cognition; early-onset Alzheimer's disease; MRI; sex characteristics
Categories
Funding
- Generalitat de Catalunya [SLT008/18/00061]
- Instituto de Salud Carlos III [FI18/00121, FI20/00076, FI21/00015, PI19/00449]
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Sex differences exist in cognitive impairment, atrophy burden, and CSF tau levels in early-onset Alzheimer's disease, with female patients showing worse symptoms.
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.
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