Target Trial Emulation for Causal Inference using LTMLE: An Application to Oral Disease and Dementia

Thomas M. Menino Convention & Exhibition Center 

Chronic, inflammatory oral diseases have increasingly been suggested as a potential modifiable risk factor for dementia, yet causal relationships remain unclear. Prior literature has relied heavily on traditional case-control and proportional hazards models that inadequately control for time-varying confounders. In this paper, we employ a target trial (TTE) framework using Longitudinal Targeted Maximum Likelihood Estimation (LTMLE), a modern causal inference method which yields more robust estimates under time-varying confounding than traditional methods. Using data from the UK Biobank, including 164,282 participants aged ≥60, we estimate the causal effect of oral disease exposure timing on the 25-year incident dementia risk. We find that those exposed at baseline, 5 years, and 10 years demonstrate a consistent 22-24% increased 25-year risk of dementia compared to those not exposed (RRs: 1.22–1.24; 95% CIs 1.02–1.50). Overall, our findings are consistent with a causal relationship between long-term oral disease exposure and elevated dementia risk, underscoring the importance of early oral intervention and further research into oral disease-modifying treatment.

causal inference

target trial emulation

Dementia

large-scale prospective cohort comprising extensive genomic, phenotypic, and longitudinal health data with decades of follow-up

Longitudinal Targeted Maximum Likelihood Estimation (LTMLE)

oral disease 

Section on Statistics in Epidemiology