ArticlemedRxiv : the preprint server for health sciences2024
DNA Methylation Age Acceleration Mediates the Relationship between Systemic Inflammation and Cognitive Impairment.
Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Chronic inflammation and DNA methylation are potential mechanisms in dementia etiology. The linkage between inflammation and DNA methylation age acceleration in shaping dementia risk is understudied. We explored the association of inflammatory cytokines with cognitive impairment and whether DNA methylation age acceleration mediates this relationship. Methods: In a subset of the 2016 wave of the Health and Retirement Study (n=3,346, age>50), we employed logistic regression to estimate the associations between each inflammatory cytokine (interleukin-6 (IL-6), C-reactive protein (CRP), and insulin-like growth factor-1 (IGF-1)), and both Langa-Weir classified cognitive impairment non-dementia and dementia, respectively. We calculated DNA methylation age acceleration residuals by regressing GrimAge on chronologic age. We tested if DNA methylation age acceleration mediated the relationship between systemic inflammation and cognitive impairment, adjusting for sociodemographic, behavioral factors, chronic conditions, and cell type proportions. Results: The prevalence of cognitive impairment was 16%. In the fully-adjusted model, participants with a doubling of IL-6 levels had 1.12 (95% CI: 1.02-1.22) times higher odds of cognitive impairment. Similar associations were found for CRP and IGF-1. Participants with a doubling of IL-6 levels had 0.77 (95% CI: 0.64, 0.90) years of GrimAge acceleration. In mediation analyses with each cytokine as predictor separately, 17.7% (95% CI: 7.0%, 50.9%) of the effect of IL-6 on cognitive impairment was mediated through DNA methylation age acceleration. Comparable mediated estimates were found for CRP and IGF-1. Conclusions: Systemic inflammation is associated with cognitive impairment, with suggestive evidence that this relationship is partially mediated through DNA methylation age acceleration.
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