Causal effects of oral disease timing on 25-year dementia risk: a longitudinal targeted maximum likelihood estimation approach

Oral diseases, including inflammatory conditions affecting the teeth and their supporting structures, have increasingly been recognized as potential modifiable risk factors for dementia. However, methodological limitations in previous studies, particularly inadequate control of time-varying confounding, have hindered causal interpretation. The objective of this study was to evaluate the causal effect of oral disease onset timing on 25-yr dementia risk using longitudinal targeted maximum likelihood estimation within a target trial emulation framework. Data were obtained from the UK Biobank and included 161, 601 participants aged \(\ge\) 60 years. Oral disease and dementia outcomes were identified using ICD-10 codes. Analyses were adjusted for demographic, behavioral, and comorbidity-related covariates. Counterfactual risks were estimated under prespecified exposure regimes representing different timings of oral disease onset. Among the supported counterfactual regimes, earlier oral disease onset (at baseline, year 5, or year 10) was associated with a 20%–22% higher risk of dementia compared with no oral disease exposure (risk ratios [RRs]: 1.20–1.22; 95% confidence intervals [95% CIs]: 1.00–1.47). Although the absolute risk differences were modest (approximately 0.8%–0.9%), they did not reach statistical significance. Earlier oral disease onset was associated with a modest increase in long-term dementia risk. These findings suggest that oral disease may represent a potential, modifiable risk factor for dementia prevention.