Accelerated Epigenetic Aging in Peripheral Blood Does not Predict Dementia Risk.

BACKGROUND There is strong evidence that epigenetic age acceleration is associated with increased risk of later-life diseases and all-cause mortality. However, there is currently limited evidence that suggests accelerated epigenetic age is associated with dementia risk. OBJECTIVE This study aims to clarify whether epigenetic biomarkers of accelerated aging can pre- dict dementia risk, which is an important consideration as aging is the greatest risk factor for the disease. METHODS DNA methylation was measured in peripheral blood samples provided by 160 partici- pants from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic de- mentia cases and 87 controls matched for age, sex, and smoking and education status. Epigenetic age was calculated using Horvath, Hannum, GrimAge and PhenoAge DNA methylation clocks, and age acceleration (the disparity between chronological age and epigenetic age) was determined. RESULTS There was no difference in age acceleration between dementia cases and controls. In males, only Hannum's intrinsic epigenetic age acceleration was increased in pre-symptomatic de- mentia cases compared to controls (Δ +1.8 years, p = 0.03). CONCLUSION These findings provide no strong evidence that accelerated epigenetic aging measured in peripheral blood can predict dementia risk.