Poor Oral Health Associated With Increased Brain Atrophy

Guido J. Falcone, MD, MPH

Findings from a cross-sectional study of middle-aged British people without stroke or dementia found that individuals with poor oral health had higher white matter volume (WMH) and worse white matter architecture profiles, even after adjusting for confounding factors. Furthermore, Mendelian randomization (MR) analyses from the study completed in the genetic phase confirmed these findings and provided evidence to support the notion that the observed association between poor oral health and poorer neuroimaging profiles is causal.¹

Published in Neurology, the study included 40,175 persons (mean age, 55 years) enrolled from 2006 to 2010, who underwent a dedicated research brain MRI between 2014 and 2016. Of these, 5470 (14%) had clinically poor oral health, which included 4954 (12%) individuals with dentures and 717 (1.8%) with loose teeth.

Using univariable linear regression analyses, data revealed that poor oral health was significantly associated with a 46% increase in WMH volume (ß = 0.46 [SD, 0.016]; P <.001), a 41% change in aggregate fractional anisotropy (FA) scores (ß = 0.41 [SD, 0.016]; P <.001), and a 42% change in aggregate mean diffusivity (MD) scores (ß = 0.42 [SD, 0.016]; P <.001). Although attenuated, these results remained significant in additional multivariable linear regression models that adjusted for age, sex, and race/ethnicity. Similarly, results remained significant after adjusting for vascular risk factors and prior cardiovascular comorbidities.

"Confirmation of our findings through follow-up observational studies, genetic analyses in other populations, and clinical trials is necessary to confirm the association between oral and brain health and to evaluate the potential impact of therapeutic interventions,” senior investigator Guido J. Falcone, MD, MPH, director of Clinical Research in Neurocritical Care at Yale University, and colleagues, wrote. "Of importance, poor oral health is highly prevalent in both developed and developing countries, and there are effective and affordable strategies to improve it."

After testing for the association between self-reported poor oral health and MRI neuroimaging markers, investigators followed up with an MR analyses to test for the association between genetically determined poor oral health and the same neuroimaging markers. In the primary analysis using the inverted weighted MR method, genetically determined poor oral health was associated with a 30% increase in WMH volume (ß = 0.30 [SD, 0.06]; P <.001), a 43% change in aggregate FA score (ß = 0.43 [SD, 0.06]; P <.001), and a 10% change in aggregate MD score (ß = 0.10 [SD, 0.03]; P <.01).

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While the MR-PRESSO global test suggested the presence of pleiotropy (P < 0.01 for the 3 outcomes), the MR-PRESSO outlier-corrected estimates, obtained after removal of the single nucleotide variants (SNVs) causing the pleiotropy, remained highly significant for all outcomes. After identifying and removing the SNVs causing the pleiotropy, genetically determined poor oral health was still associated with a 37% increase in WMH volume (β = 0.37 [SD, 0.06] P < 0.001), a 45% change in aggregate FA score (β = 0.45 [SD, 0.06] P < 0.001), and an 8% change in aggregate MD score (β = 0.08 [SD, 0.03] P = 0.01).

In a secondary analysis of 48 brain regions separately, results indicated that genetically determined poor oral health was associated with FA or MD changes in most of the tracts, even after adjusting for multiple testing. The retrolentricular part of the internal capsule emerged as the region with the most significantly altered microarchitecture (right retrolenticular part FA p = 5 × 10−15; MD p = 3 × 10−20; left retrolenticular part FA p = 4 × 10−11; MD p = 9 × 10−17).

"Further translational research is necessary to elucidate the pathophysiologic mechanisms that mediate the relationship between poor oral health and brain health outcomes," the study authors noted. "One potential mechanism is systemic inflammation, which is commonly observed in patients with periodontal disease. Bacterial invasion of the gums can lead to the production of inflammatory mediators that enter the bloodstream, con- tributing to systemic inflammation. Moreover, denture bio- film, containing a higher concentration of yeasts such as Candida albicans, has been implicated in inflammatory dis- eases such as denture stomatitis."

REFERENCE
1. River CA, Renedo DB, Havenon A, et al. Association of poor oral health with neuroimaging markers of white matter injury in middle-aged participants in the UK Biobank. Neurology. 2024;102(2). doi:10.1212/WNL.00000000000208010