Purpose of mediation used in the study. Directed acyclic graph theorizing possible etiological relationships. The graph is not exhaustive. The effect of cystatin C on neurocognitive abnormalities (global cognition at TILDA Wave 1, cognitive score reduction between Wave 1 and Wave 3) in the study cohort is exercised as an example. The estimates represent the total and decomposed effects of kidney function in a one mg/mL unit increase of plasma cystatin C transformed to its base natural logarithms (ln-cystatin C). A cardiovascular biomarker score (Cardiovascular BS) is tested as a mediator. The analyses were based on a multivariable linear regression model adjusted for age, demographics (sex, education, depression), and clinical vascular risk factors (i.e. smoking, obesity, systolic blood pressure, diastolic blood pressure, number of CVD risk factors, diabetes mellitus, total cholesterol level, HDL-cholesterol level, C-reactive protein level). Mediation results for vascular markers are described in Table 4 (Panels A and B).