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 predict
dementia risk, which is an important consideration as aging is the greatest risk factor for the
Methods: DNA methylation was measured in peripheral blood samples provided by 160 participants
from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic dementia
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 dementia
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.