Divergent effects of oral health and genetic risk: competing risks of dementia and mortality.

Abstract

Polygenic risk scores (PRS) for dementia are increasingly used to capture genetic susceptibility, yet their predictive utility may depend on coexisting health and social conditions. Edentulism, an extreme marker of oral health deterioration and accumulated disadvantage, may influence how genetic risk manifests in later life. This study aims to investigate the independent and joint associations of edentulism and dementia PRS with incident all-cause dementia and mortality risk. We analyzed longitudinal data from the Health and Retirement Study linked to Medicare claims. The sample included 9,806 dementia-free participants aged ≥67 with information on edentulism and PRS for Alzheimer's disease. Edentulism was self-reported and logically imputed across waves. PRS was categorized as low, intermediate, and high. Outcomes included incident dementia and all-cause mortality. Cox proportional hazards and Fine-Gray competing risk models were used to examine independent and interactive associations. Edentulism was not independently associated with dementia risk after full adjustment. High PRS was associated with increased dementia risk (subdistribution hazard ratio [sHR] 1.20; 95% confidence interval [CI], 1.06-1.39). However, the association between PRS and dementia was weaker among edentulous participants (interaction sHR 0.73; 95% CI, 0.54-0.99). In contrast, mortality risk was higher among individuals with both edentulism and high PRS (interaction sHR 1.36; 95% CI, 1.00-1.84). These findings suggest that oral health status may modify the association between genetic risk and dementia in late life. Mortality may occur before a diagnosis of dementia, underscoring the importance of considering competing health risks when interpreting genetic susceptibility in aging populations.