Oral health, genetic susceptibility, and risk of dementia: a prospective cohort study of UK Biobank.

Poor oral health and genetic susceptibility have each been linked to dementia risk, but their joint effects and subtype-specific associations remain unclear. To examine the independent and combined associations of oral health indicators and genetic susceptibility with incident dementia, we conducted a prospective cohort study using UK Biobank data. A total of 364,557 predominantly White European adults aged 38-73 years who were free of dementia at baseline (2006-2010) and had complete oral health and genetic data were followed for incident dementia through 2022. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), and interactions were evaluated. Over a median follow-up of 13.64 years, 7,553 participants developed all-cause dementia (ACD), including 3,277 Alzheimer's disease (AD) and 1,578 vascular dementia (VaD). Painful gums (HR 1.26, 95% CI 1.12-1.42) and denture use (HR 1.20, 95% CI 1.13-1.26) were associated with higher ACD risk, with comparable associations observed for AD and VaD. Toothache was associated with ACD (HR 1.24, 95% CI 1.11-1.39) and AD (HR 1.21, 95% CI 1.01-1.45) but not VaD. Dementia risk increased with the number of oral conditions. Higher genetic risk was independently associated with dementia, and moderate additive interactions were observed between oral health and genetic risk. These findings suggest that poor oral health was independently associated with higher risks of ACD, AD, and VaD and may amplify dementia risk among genetically susceptible individuals. Oral health may represent a potentially modifiable factor associated with dementia risk, but its causal role in dementia prevention should be tested in mechanistic and interventional studies.