Periodontal disease, biomarkers of ADRD risk, and cognitive functioning

BACKGROUND: Periodontitis is a hypothesized risk factor for cognitive impairment. Many prior studies lack information on biological markers of Alzheimer's disease and related dementias (ADRD) risk or genetic risk markers. We assessed the association between periodontitis, biological markers of ADRD risk, and cognitive test performance with robust adjustment for risk factors including high risk genotypes for ADRD. METHODS: We use data from the United States High School and Beyond (HS&B:80) cohort study, a nationally representative sample of ∼26,830 people enrolled during high school in 1980 through midlife in 2021. Baseline data include information about educational contexts, opportunities, and outcomes; early life circumstances; and demographic group memberships. HS&B:80 data from 2021 include indicators of periodontal disease diagnosis history, blood biomarkers of ADRD risk, and multiple measures of cognitive functioning. We calculated false discovery rates (FDR) to account for multiple comparisons. RESULTS: Our analyses included 13,950 HS&B:80 panelists (mean age 58 years), among whom 15.2% reported a history of periodontal disease. Periodontal disease was associated with lower general cognitive functioning and scores on some domain-specific cognitive tasks; it was also associated with increased levels of pTau-181 and C-reactive protein. We find no evidence of heterogeneity in associations by sex, race and ethnicity, or number of apolipoprotein E (APOE) ε4 alleles. Only working memory attained a FDR < 10% after multiple comparisons adjustment. CONCLUSION: In this large, diverse, population-representative, community-dwelling sample, self-reported periodontal disease was cross-sectionally associated with cognitive functioning at age ∼60 and some biomarkers of ADRD risk although most associations were not significant after multiple comparisons corrections. PLAIN LANGUAGE SUMMARY: Poor gum health has been suggested as a possible contributor to memory and thinking problems later in life, but many studies have not been able to account for important biological and genetic risk factors linked to Alzheimer's disease and related dementias. To better understand this relationship, we analyzed data from nearly 14,000 participants in a large, nationally representative U.S. study who were approaching age 60 in 2021. About 15% reported having been diagnosed with periodontal (gum) disease. People with a history of gum disease tended to perform slightly worse on measures of overall cognitive function and some specific thinking tasks. They also had modestly higher levels of blood markers associated with inflammation and increased risk of Alzheimer's disease and related dementias. These associations were similar across men and women, racial and ethnic groups, and people with different levels of genetic risk based on apolipoprotein E (APOE) status. While this study cannot determine whether gum disease causes cognitive decline, the findings suggest that poor periodontal health may be potentially linked to both cognitive performance and biological signs associated with dementia risk in midlife, highlighting the importance of future research that can better understand if these observations are causal or coincidental.