Mediation Analysis of White Blood Cell Count on the Association Between Periodontal Inflammation and Digit Symbol Substitution Test Scoring Cognitive Function Among Older U.S. Adults

Background Systemic effects of periodontal infection may increase the risk of central neuroinflammation, aggravating impaired cognition. This study aims to examine whether systemic inflammatory factors mediate the possible association between periodontal inflammation and cognitive function. Methods We conducted a cross-sectional analysis of 766 participants aged > 60 years and who had complete periodontal and cognitive examinations in the NHANES 2001-2002. We used multivariable linear regression to investigate the overall association between periodontal health and cognitive function as measured by the digit symbol substitution test (DSST). Bleeding on probing (BOP) and periodontal inflamed surface area (PISA) were used to assess the periodontal inflammatory activity and burden, respectively. Mediation analyses were used to test the indirect effects of the BOP/PISA on DSST via C-reactive protein, white blood cell (WBC) count, and fibrinogen. Results Participants with superior periodontal health obtained higher DSST scores than those with poorer periodontal health, adjusting for demographic factors and chronic conditions. Concerning the inflammatory activity, WBC count acted as a full mediator in the association between BOP and DSST (β = -0.091; 95% CI = -0.174 to -0.008) and mediated 27.5% of the total association. Regarding the inflammatory burden, WBC count acted as a partial mediator in the association between PISA and DSST (β = -0.059; 95% CI = -0.087 to -0.031) and mediated 20.3% of the total association. Conclusion Our study indicated the potential role of systemic inflammatory factors as a mediator of associations between periodontal inflammation and cognitive function in the U.S. geriatric population.