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 disease.

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.

背景：有强有力的证据表明，表观遗传年龄加速与晚年疾病和全因死亡率的风险增加有关。然而，目前有限的证据表明加速表观遗传年龄与痴呆风险有关。

目的：本研究旨在阐明加速衰老的表观遗传生物标志物是否可以预测痴呆风险，这是一个重要的考虑因素，因为衰老是该疾病的最大风险因素。

方法：在阿司匹林减少老年人事件研究中的 160 名参与者提供的外周血样本中测量 DNA 甲基化，包括 73 名症状前痴呆病例和 87 名年龄、性别、吸烟和教育状况匹配的对照。使用 Horvath、Hannum、GrimAge 和 PhenoAge DNA 甲基化时钟计算表观遗传年龄，并确定年龄加速（实足年龄和表观遗传年龄之间的差异）。

结果：痴呆病例和对照组之间的年龄加速没有差异。在男性中，与对照组相比，症状前痴呆病例中只有 Hannum 的内在表观遗传年龄加速增加（Δ +1.8 岁，p = 0.03）。

结论：这些发现没有提供强有力的证据表明在外周血中测量的加速表观遗传衰老可以预测痴呆风险。