Accelerated biological aging mediates the association between periodontal disease and cognitive function in older adults

Background and Objectives Periodontitis is a prevalent chronic inflammatory gum disease in older adults and has been linked to cognitive decline, but underlying mechanisms are unclear. The geroscience hypothesis provides a framework for this link, positing that fundamental aging processes (eg, chronic inflammation) drive multiple age-related diseases. We aimed to determine whether accelerated biological aging mediates the association between periodontal disease and cognitive function in older adults. Research Design and Methods Data were analyzed from 1950 adults aged ≥60 years in the National Health and Nutrition Examination Survey 1999-2002. Periodontal status was clinically assessed (mean clinical attachment loss [CAL], periodontal probing depth [PD], and periodontitis defined by CDC/AAP thresholds). Cognitive performance was measured with the Digit Symbol Substitution Test (DSST). Biological aging was quantified using Klemera-Doubal method (KDM) and Phenotypic Age (PhenoAge) algorithms. Multivariable linear regressions and mediation analyses (adjusted for sociodemographic, behavioral, and health factors) were conducted to evaluate associations and the proportion of the periodontal-cognition link mediated by biological age acceleration (BAA). Results Periodontitis was significantly associated with poorer cognitive function (DSST standardized β=-0.095, P <. 01) and higher KDM-BAA (β = 0.812, P <. 001) and PhenoAge Acceleration (β = 1.004, P <. 001). Each 1-mm increase in CAL was associated with lower DSST scores (β=-0.048, P <. 01), greater KDM-BAA (β = 0.221, P =. 031), and higher PhenoAge Acceleration (β = 0.475, P <. 001). Higher BAA was independently associated with lower cognitive scores (KDM-BAA β=-0.009, P =. 021; PhenoAge Acceleration β=-0.008, P =. 003). Mediation analyses showed KDM-BAA and PhenoAge Acceleration mediated approximately 5.7%-15.1% (all indirect effects P <. 05) of the total periodontal-cognition relationship. Discussion and Implications Accelerated biological aging partially mediates the relationship between periodontal disease and cognitive function, supporting a novel geroscience-based mechanism linking oral inflammation and cognitive decline. Future interventions targeting oral health could simultaneously mitigate systemic aging and protect cognitive function.

Duke Scholars

Author Bei Wu School of Nursing