A multimodal study on the effect of sex on Alzheimer's disease clinical and biomarker changes in adults with Down syndrome

Abstract Background The study of sex differences in Alzheimer's disease (AD) is gaining increasing attention. Yet, few studies have examined the effect genetically determined forms AD. Here, we explored impact on AD‐related clinical and biomarker changes a population‐based cohort adults with Down syndrome, who lifetime risk over 90% to develop Method This cross‐sectional 549 syndrome. We compared AD prevalence, as well cognitive changes, relation age whole cohort. Participants underwent neuropsychological examination Cambridge Cognitive Examination for Older Adults Syndrome (CAMCOG‐DS) modified cued recall test (mCRT). Most also had at least one assessment amyloid pathology (CSF Aβ42, Aβ42/40 ratio amyloid‐PET), tau plasma p‐Tau‐181) neurodegeneration NfL, FDG‐PET 3T structural MRI). used within‐group locally estimated scatterplot smoothing (LOESS) models compare trajectory women versus men, interaction APOE ε4 allele. Result prevalence across five‐year intervals mean diagnosis was similar between men women. Men trajectories CAMCOG scores age, but showed lower mCRT from 45 years. There were no CSF or amyloid‐PET, biomarkers. When considering genotype, carrying allele an earlier higher symptomatic ages 40‐45 non‐carriers. female advantage lost Conclusion Sex did not main changes. However, age‐related women, men. These results emphasize complexity relationship biological AD, need further explore interactions ε4.