Aging
The Role of DNA methylation-based Biological Aging, Immunity and Inflammation Biomarkers in the Relationship between Stroke, Short- and Long-term Cognition. Reem Waziry* Reem Waziry
Objective. To determine indirect effects of stroke on short- and long-term cognition in relation to inflammation, immunity and aging.
Methods. The study population included individuals who consented for blood draw in the Health and Retirement 2016 Venous blood study. 3, 467 individuals were included. Indirect effects of stroke on short- and long-term cognition with respect to select biological biomarkers with a focus on inflammation, immunity and DNA methylation based biological aging were assessed using four-way decomposition models. Direct and indirect effects of APOE 4 carriership, as a risk factor gene, on cognition in relation to stroke were also assessed.
Results. Pure natural indirect effects of stroke on short-term cognition in relation to key biological biomarkers were as follows: inflammatory biomarkers: beta=-0.01 (P value=0.250), immunity biomarkers: -0.04 (P value =0.002), White Blood Cells: -0.04 (P value= 0.016), DNA methylation-based biological aging: -0.41 (P value < 0.001), and all biomarkers jointly: -0.38 (P value < 0.001).
Reference interaction effects of stroke on short-term cognition in relation to key biological biomarkers were as follows: TGF-beta: beta= -2.13 (P value <0.001); immunity: 3.51 (P value=0.260); White Blood Cells: 0.04 (P value= 0.910); DNA methylation-based biological age:-0.25 (P value < 0.01), and all biomarkers jointly: 11.98 (P value= 0.01).
Conclusions. Stroke effects on cognition are partially through mediation and interaction with key inflammatory, immunity and biological aging biomarker pathways. Therapeutics targeting joint pathways are likely essential to optimize cognitive resilience especially in stroke survivors.