Periodontitis and cognitive impairment in older adults: The mediating role of mitochondrial dysfunction

Background: Increased attention has been focused on the associations of periodontal disease with the onset and progression of cognitive impairment. Although the associations are likely to be multifactorial, few studies have explored the role of mitochondrial dysfunction in the periodontitis-dementia link.

Methods: Cross-sectional data of 1,883 participants aged ≥60 years in the National Health and Nutrition Examination Survey 2011‒2014 were analyzed. The following data were collected: 1) general information on sociodemographic, behavioral, and health-related factors; 2) periodontal status (mean attachment loss [AL] and mean probing depth [PD]); 3) mitochondrion-derived biomarker of mitochondrial dysfunction (blood sample concentration of methylmalonic acid [MMA]); 4) cognitive function (Consortium to Establish a Registry for Alzheimer's disease immediate recall [CERAD-IR] and delay recall [CERAD-DR], animal fluency test, and digit symbol substitution test [DSST]). Mediation analysis weighted for complex survey design was used to assess the effect of MMA on the association of periodontal status with cognitive function after adjusting for potential confounders.

Results: Participants with Stage III and IV periodontitis had lower scores on cognitive performance and higher MMA levels than those with Stages I/II periodontitis. Circulating MMA was significantly associated with CERAD-DR (weighted β [SE] = −0.076 [0.011]) and DSST (weighted β [SE] = −0.039 [0.009]), which mediated 9.9% and 6.0% of the total association of mean PD with cognitive function. Moreover, MMA mediated 11.7% and 5.8% of the association of mean AL with CERAD-DR and DSST, respectively.

Conclusion: The findings suggest that MMA, a biomarker of mitochondrial dysfunction, plays a mediating role in the link between periodontitis and cognitive impairment in older adults aged ≥60 years.