Abstract 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.
Background Porphyromonas gingivalis peptidyl-arginine deiminase (PPAD) enzyme has been implicated in rheumatoid arthritis (RA) pathogenesis through protein citrullination and its potential contribution to neutrophil-associated inflammatory responses and anti-citrullinated protein antibody (ACPA) autoimmunity. However, its role in early stages of RA remains unclear. This study investigated the association of PPAD with citrullinated histone H3 (CitH3), cathelicidin (LL-37), and ACPA in preclinical RA (preRA), early RA (eRA), and established RA (RA), with and without periodontitis (PD).Methods 108 participants were categorized into preRA, eRA, RA, and nonRA controls with and without PD. Periodontal and rheumatological parameters were assessed. ppad gene expression was quantified in subgingival plaque samples, and salivary and serum levels of CitH3, LL-37 and ACPA were measured. Data were analyzed with SPSS version 26.Results ppad expression was elevated in all PD groups, irrespective of RA status. Among PD groups, ppad correlated with salivary CitH3 only in eRA-PD (r = 0.628) and with serum ACPA only in RA-PD (r = 0.503), while no significant associations were detected between ppad and LL-37. CitH3 was not associated with serum ACPA in any PD group. As secondary findings, salivary CitH3 correlated with gingival bleeding index (GBI) in eRA-PD (r = 0.628) and RA-PD (r = 0.608) while serum LL-37 correlated with serum ACPA in eRA-PD (r = 0.767),Conclusion Elevated ppad expression was primarily associated with PD rather than RA status. PPADs association with salivary CitH3 in eRA-PD suggests its strong role in periodontal inflammation during early phases of RA but disproves a mechanistic link between PPAD to NETs and RA.
Background Population-level evidence on associated factors for mid-buccal gingival recession (GR) severity stratified by periodontitis status remains limited. This study assessed the prevalence and severity of GR in United States (US) adults and identified associated factors. Methods Data from 5891 dentate adults (>= 30 years) from the National Health and Nutrition Examination 2011-2014, representing 129.6 million US adults, were analyzed. GR prevalence and severity were defined using mm-based cutoffs (no GR, <3, <5, >= 5 mm) and the Cairo et al. classification (no GR, recession type [RT] 1/RT2, RT3). Survey-weighted ordinal logistic regression models were stratified by periodontitis status (American Academy of Periodontology case definition) for the mm-based outcome (p < 0.05). Results Weighted GR prevalence was 91.1% (>= 1 mm), 37.2% (>= 3 mm), and 6.0% (>= 5 mm), and RT1/RT2/RT3 prevalence was 7.3%, 88.2%, and 58.7%, respectively. Age was associated with GR across models, with the largest effect in participants with periodontitis (>= 65 years: odds ratio [OR] = 5.0, 95% confidence interval [CI]: 3.4-7.4). Male s predicted higher GR severity across all models (OR = 1.1-1.7). Within the periodontitis stratum, current smoking (OR = 2.1; 95% CI: 1.5-2.9) and lower educational level were associated with GR. In the Cairo et al.-based model, periodontitis (OR = 3.3; 95% CI: 2.7-3.9) and current smoking (OR = 1.6; 95% CI: 1.3-1.9) predicted more severe recession types (all p < 0.001). Conclusions Mid-buccal GR severity in US adults shows distinct risk patterns by periodontitis status, with age and se as associated factors in both groups and current smoking as an associated factor in participants with periodontitis. Targeted prevention and risk-based management strategies may help reduce the burden of severe GR.
Abstract Background This scoping review evaluates the recovery pattern of host responses, in terms of immune regulation and tissue remodeling, in gingival crevicular fluid (GCF) during experimental gingivitis (EG) resolution phase. Methods Electronic database and hand searches were conducted to screen the literature published from January 1960 to December 2024. The selected studies were randomized and non‐randomized controlled trials evaluating the changes of clinical parameters and host responses in GCF mediators during EG, focusing on the baseline and the resolution phase. Due to the heterogeneity of the included studies, a meta‐analysis was not conducted. Evidence quality and risk of bias were assessed. Results A total of 17 studies with 303 volunteers met the inclusion criteria, analyzing four clinical parameters and 58 biomarkers in GCF samples. Pro‐inflammatory cytokines and mediators associated with tissue remodeling, such as IL‐1α, IL‐1β, MMP‐8, and ALP increased during EG induction and decreased during EG resolution, similar to the trends in the clinical parameters. In contrast, the levels of MIP‐1β and IL‐10 were reduced during EG induction and elevated during EG resolution. In addition, the levels of IL‐1β and ALP were able to return to baseline level at the end of the resolution phase. Conclusions This scoping review showed that, following an average EG resolution period of 7 to 21 days, clinical signs of inflammation improved or restored. Notably, IL‐1β and ALP exhibited a return of levels to their pre‐disease (baseline) state, suggesting their potential as indicators for monitoring dynamic changes in inflammatory status at the molecular level during EG resolution.
