Abstract
Background: Oral health is a modifiable risk factor for stroke. However, the role of oral health in the brain health of clinically asymptomatic persons remains understudied. We hypothesize that genetically-determined poor oral health leads to worse neuroimaging brain health profiles in persons without stroke. Methods: We conducted a two-sample Mendelian Randomization (MR) study. As instruments, we used 105 genetic variants known to be associated (p<5x10 -8 ) with a composite of caries, dentures and missing teeth in the GLIDE Consortium. In stroke-free participants enrolled in the UK Biobank, we tested for association between these genetic variants and white matter hyperintensity volume (natural log-transformed), fraction anisotropy and mean diffusivity. For the last two neuroimaging traits, we evaluated the first principal component of measurements obtained across 48 brain regions. Results: Our primary analysis using the inverse variance-weighted MR method indicated that genetically-increased risk of poor oral health was associated with: (1) higher burden of silent cerebrovascular disease, as represented by higher volumes of white matter hyperintensities (beta=0.24, SE=0.07 p-value=0.001), and (2) increased microstructural damage, as represented by lower fractional anisotropy (beta=-2.53, SE=0.38; p=1x10 -9 ) and higher mean diffusivity (beta=3.42, SE=0.41; p=2x10 -11 ). Sensitivity analyses identified horizontal pleiotropy in our primary results, but an outlier-corrected analysis confirmed all three initial results (all p-values <0.001, Table 1). Conclusion: Among persons without stroke, genetically-determined poor oral health is associated with worse neuroimaging brain health profiles. Because gene-disease associations are immune to confounding, our results indicate that this association is causal. Early treatment of poor oral health may lead to significant brain health benefits, even in persons without stroke.
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