Blood DNA methylation levels of the oxytocin promoter predict conversion from mild cognitive impairment to dementia in females within a clinical cohort of cognitive complaints

Recent studies have highlighted the role of oxytocin (OXT) in Alzheimer’s disease (AD) dementia and demonstrated its potential as a therapeutic target to reverse cognitive impairment and mitigate AD pathology. Epigenetic dysregulation of OXT has been identified in brain tissue from AD patients, and DNA methylation levels of the exact same locus in the blood of healthy aged individuals have shown predictive biomarker value for conversion to AD. Building on these insights, we investigated the DNA methylation status of the OXT promoter in blood in a prospective cohort of consecutive patients from the BioBank Alzheimer Center Limburg (BBACL). This cohort included males and females suffering from subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Our findings revealed that DNA methylation levels of the OXT promoter at baseline predict the conversion from MCI to dementia in female participants. In addition to discovering differences in the OXT promoter related to sex, we also observed alterations associated with aging, alcohol consumption, and smoking. Overall, our findings underscore the implications of OXT and its DNA methylation changes in blood within the context of dementia.