Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-wide association study identified DNA methylation correlates of C-reactive protein (CRP)—a widely used acute-phase inflammatory biomarker. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure. We utilise a DNA methylation-based score for CRP and investigate its trajectories with age, and associations with cognitive ability in comparison with serum CRP and a genetic CRP score in a longitudinal study of older adults (n = 889) and a large, cross-sectional cohort (n = 7028). We identified no homogeneous trajectories of serum CRP with age across the cohorts, whereas the epigenetic CRP score was consistently found to increase with age (standardised β = 0.07 and 0.01) and to do so more rapidly in males compared to females. Additionally, the epigenetic CRP score had higher test-retest reliability compared to serum CRP, indicating its enhanced temporal stability. Higher serum CRP was not found to be associated with poorer cognitive ability (standardised β = − 0.08 and − 0.05); however, a consistent negative association was identified between cognitive ability and the epigenetic CRP score in both cohorts (standardised β = − 0.15 and − 0.08). An epigenetic proxy of CRP may provide a more reliable signature of chronic inflammation, allowing for more accurate stratification of individuals, and thus clearer inference of associations with incident health outcomes.

中文翻译：

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炎症相关表观遗传评分的表征及其与认知能力的关联。

慢性全身性炎症与痴呆症有关，但其与年龄相关的认知能力下降的关系尚不清楚。许多炎症生物标志物的急性反应意味着它们可能提供不可靠的慢性炎症图像。最近，一项大规模的表观基因组关联研究确定了 C 反应蛋白 (CRP) 的 DNA 甲基化相关性，CRP 是一种广泛使用的急性期炎症生物标志物。DNA甲基化被认为在短期内相对稳定，将其标记为潜在有用的暴露特征。我们利用基于 DNA 甲基化的 CRP 评分，并在一项针对老年人 (n = 889) 的纵向研究和一项大型交叉研究中，研究其与年龄的轨迹，以及与血清 CRP 和遗传 CRP 评分相比与认知能力的关联。部分队列（n = 7028）。我们没有发现血清 CRP 随年龄变化的同质轨迹，而表观遗传 CRP 评分始终随年龄增加（标准化 β = 0.07 和 0.01），并且与女性相比，男性的增加速度更快。此外，与血清 CRP 相比，表观遗传 CRP 评分具有更高的重测信度，表明其增强的时间稳定性。未发现较高的血清 CRP 与较差的认知能力相关（标准化 β = - 0.08 和 - 0.05）；然而，在两个队列中发现认知能力和表观遗传 CRP 评分之间存在一致的负相关（标准化 β = - 0.15 和 - 0.08）。CRP 的表观遗传代理可以提供更可靠的慢性炎症特征，从而可以更准确地对个体进行分层，