Faculty Bibliography

Diabetes mellitus (DM) is a recognized risk factor for dementia, and increasing evidence shows that tooth loss is associated with cognitive impairment and dementia. However, the effect of the co-occurrence of DM and edentulism on cognitive decline is understudied. This 12-y cohort study aimed to assess the effect of the co-occurrence of DM and edentulism on cognitive decline and examine whether the effect differs by age group. Data were drawn from the 2006 to 2018 Health and Retirement Study. The study sample included 5,440 older adults aged 65 to 74 y, 3,300 aged 75 to 84 y, and 1,208 aged 85 y or older. Linear mixed-effect regression was employed to model the rates of cognitive decline stratified by age cohorts. Compared with their counterparts with neither DM nor edentulism at baseline, older adults aged 65 to 74 y (β = -1.12; 95% confidence interval [CI], -1.56 to -0.65; P < 0.001) and those aged 75 to 84 y with both conditions (β = -1.35; 95% CI, -2.09 to -0.61; P < 0.001) had a worse cognitive function. For the rate of cognitive decline, compared to those with neither condition from the same age cohort, older adults aged 65 to 74 y with both conditions declined at a higher rate (β = -0.15; 95% CI, -0.20 to -0.10; P < 0.001). Having DM alone led to an accelerated cognitive decline in older adults aged 65 to 74 y (β = -0.09; 95% CI, -0.13 to -0.05; P < 0.001); having edentulism alone led to an accelerated decline in older adults aged 65 to 74 y (β = -0.13; 95% CI, -0.17 to -0.08; P < 0.001) and older adults aged 75 to 84 (β = -0.10; 95% CI, -0.17 to -0.03; P < 0.01). Our study finds the co-occurrence of DM and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65 to 74 y.

BACKGROUND:Periodontal disease (PerioD) is a chronic, complex inflammatory condition resulting from the interaction between subgingival dysbiotic bacteria and the host immune response leading to local inflammation. Since periodontal inflammation is characterized by multiple cytokines effects we investigated whether Periodontal Inflamed Surface Area (PISA), a continuous measure of clinical periodontal inflammation is a predictor of composite indexes of salivary cytokines. METHODS AND FINDINGS/RESULTS:In a cross-sectional study of 67 healthy, well-educated individuals, we evaluated PISA and several cytokines expressed in whole stimulated saliva. Two salivary cytokine indexes were constructed using weighted and unweighted approaches based on a Principal Component Analysis [named Cytokine Component Index (CCI)] or averaging the (standardized) level of all cytokines [named Composite Inflammatory Index (CII)]. In regression analysis we found that PISA scores were significantly associated with both salivary cytokine constructs, (CCI: part R = 0.51, p<0.001; CII: part R = 0.40, p = 0.001) independent of age, gender and BMI showing that single scores summarizing salivary cytokines correlated with severity of clinical periodontal inflammation. CONCLUSIONS:Clinical periodontal inflammation may be reflected by a single score encompassing several salivary cytokines. These results are consistent with the complexity of interactions characterizing periodontal disease. In addition, Type I error is likely to be avoided.

Periodontal disease (PD) is one of the most common inflammatory diseases in humans and is initiated by an oral microbial dysbiosis that stimulates inflammation and bone loss. Here, we report an abnormal elevation of succinate in the subgingival plaque of subjects with severe PD. Succinate activates succinate receptor-1 (SUCNR1) and stimulates inflammation. We detected SUCNR1 expression in the human and mouse periodontium and hypothesize that succinate activates SUCNR1 to accelerate periodontitis through the inflammatory response. Administration of exogenous succinate enhanced periodontal disease, whereas SUCNR1 knockout mice were protected from inflammation, oral dysbiosis, and subsequent periodontal bone loss in two different models of periodontitis. Therapeutic studies demonstrated that a SUCNR1 antagonist inhibited inflammatory events and osteoclastogenesis in vitro and reduced periodontal bone loss in vivo. Our study reveals succinate's effect on periodontitis pathogenesis and provides a topical treatment for this disease.

INTRODUCTION/BACKGROUND:The aim of this research was to assess the association between inflammation and oral health and diabetes, as well as the mediating role of oral hygiene practice in this association. METHODS:Data were from the 2009-2010 National Health and Nutrition Examination Survey. The analytical sample consisted of 2,191 respondents aged 50 and older. Poor oral health was clinically defined by significant tooth loss (STL) and periodontal disease (PD). Diabetes mellitus (DM) was determined by glycemic levels. The outcome variable was serum C-reactive protein (CRP) level, dichotomised as ≥1 mg/dL (elevated CRP) vs <1 mg/dL (not elevated CRP). Two path models, one using STL and DM as the independent variable, the other using PD and DM as the independent variable, were estimated to assess the direct effects of having poor oral health and DM on elevated CRP and the mediating effects of dental flossing. RESULTS:In path model 1, individuals having both STL and DM (adjusted odds ratio [AOR], 1.92; 95% confidence interval [CI], 1.30-2.82) or having STL alone (AOR, 2.30; 95% CI, 1.68-3.15) were more likely to have elevated CRP than those with neither STL nor DM; dental flossing (AOR, 0.92, 95% CI, 0.88-0.96) was associated with lower risk of elevated CRP. In path model 2, no significant association was found between having both PD and DM and elevated CRP; dental flossing (AOR, 0.91; 95% CI:, 0.86-0.94) was associated with lower risk of elevated CRP. CONCLUSIONS:Findings from this study highlight the importance of improving oral health and oral hygiene practice to mitigate inflammation. Further research is needed to assess the longer-term effects of reducing inflammation.

INTRODUCTION:Individuals with mild dementia are at high risk of poor oral health outcomes. To address this issue, we describe an intervention to teach care partners skills to guide individuals with mild dementia in proper oral hygiene techniques and provide reminders to practice oral hygiene care. By providing support to perform these tasks successfully, we aim to delay oral health decline among this vulnerable population. METHODS AND ANALYSIS:This multisite study is a three-arm randomised controlled trial. The primary objective is to evaluate the efficacy of an intervention to improve oral hygiene outcomes by promoting positive oral hygiene behaviours and skills among individuals with mild dementia. Care partners' behaviour factors, such as oral care self-efficacy and implementation of the care plan, serve as mediators of the intervention. Participant-care partner dyads will be randomly assigned to either Treatment Group 1, Treatment Group 2 or the Control Group. All groups will receive an educational booklet. Treatment Group 1 and Treatment Group 2 will receive a smart electronic toothbrush. Treatment Group 2 (the intervention group) will also receive an oral hygiene care skill assessment, personalised oral hygiene instruction and treatment plan; and care partners will receive in-home and telephone coaching on behaviour change. Oral health outcomes will be compared across the three groups. The duration of the active intervention is 3 months, with an additional 3-month maintenance phase. Data collection will involve three home visits: baseline, 3 months and 6 months. The study enrollment started in November 2021, and the data collection will end in Spring 2024. ETHICS AND DISSEMINATION:The study has been approved by the Institutional Review Board of the NYU Grossman School of Medicine and Duke University, and is registered at Clinicaltrials.gov. A Data Safety Monitoring Board has been constituted. The study findings will be disseminated via peer-reviewed publications, conference presentations and social media. TRIAL REGISTRATION NUMBER:NCT04390750.

The effect of electronic cigarette (e-cigarette) smoking, especially its long-term impact on oral health, is poorly understood. Here, we conducted a longitudinal clinical study with two study visits, 6 months apart, to investigate the effect of e-cigarette use on the bacterial community structure in the saliva of 101 periodontitis patients. Our data demonstrated that e-cigarette use altered the oral microbiome in periodontitis patients, enriching members of the Filifactor, Treponema, and Fusobacterium taxa. For patients at the same periodontal disease stage, cigarette smokers and e-cigarette smokers shared more similarities in their oral bacterial composition. E-cigarette smoking may have a similar potential as cigarette smoking at altering the bacterial composition of saliva over time, leading to an increase in the relative abundance of periodontal disease-associated pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. The correlation analysis showed that certain genera, such as Dialister, Selenomonas, and Leptotrichia in the e-cigarette smoking group, were positively correlated with the levels of proinflammatory cytokines, including IFN-γ, IL-1β, and TNF-α. E-cigarette use was also associated with elevated levels of proinflammatory cytokines such as IFN-γ and TNF-α, which contribute to oral microbiome dysbiosis and advanced disease state. This article is protected by copyright. All rights reserved.

Electronic cigarettes (e-cigs) have become prevalent as an alternative to conventional cigarette smoking, particularly in youth. E-cig aerosols contain unique chemicals which alter the oral microbiome and promote dysbiosis in ways we are just beginning to investigate. We conducted a 6-month longitudinal study involving 84 subjects who were either e-cig users, conventional smokers, or nonsmokers. Periodontal condition, cytokine levels, and subgingival microbial community composition were assessed, with periodontal, clinical, and cytokine measures reflecting cohort habit and positively correlating with pathogenic taxa (e.g., Treponema, Saccharibacteria, and Porphyromonas). α-Diversity increased similarly across cohorts longitudinally, yet each cohort maintained a unique microbiome. The e-cig microbiome shared many characteristics with the microbiome of conventional smokers and some with nonsmokers, yet it maintained a unique subgingival microbial community enriched in Fusobacterium and Bacteroidales (G-2). Our data suggest that e-cig use promotes a unique periodontal microbiome, existing as a stable heterogeneous state between those of conventional smokers and nonsmokers and presenting unique oral health challenges. IMPORTANCE Electronic cigarette (e-cig) use is gaining in popularity and is often perceived as a healthier alternative to conventional smoking. Yet there is little evidence of the effects of long-term use of e-cigs on oral health. Conventional cigarette smoking is a prominent risk factor for the development of periodontitis, an oral disease affecting nearly half of adults over 30 years of age in the United States. Periodontitis is initiated through a disturbance in the microbial biofilm communities inhabiting the unique space between teeth and gingival tissues. This disturbance instigates host inflammatory and immune responses and, if left untreated, leads to tooth and bone loss and systemic diseases. We found that the e-cig user's periodontal microbiome is unique, eliciting unique host responses. Yet some similarities to the microbiomes of both conventional smokers and nonsmokers exist, with strikingly more in common with that of cigarette smokers, suggesting that there is a unique periodontal risk associated with e-cig use.

Inflammation plays a significant role in Alzheimer's disease (AD) pathogenesis. Studies have shown that systemic, peripheral infections affect AD patients. Cognitive dysfunction is a consistent finding in AD and periodontal disease is a chronic, peripheral infection often resulting in tooth loss. We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few missing teeth. The effect of PI/tooth loss on cognitive function [measured by Digit Symbol (DST) and Block Design (BDT) tests] was assessed in 70-year old Danish subjects. We found: 1) subjects with PI obtained lower mean DST scores compared to subjects without PI (p < 0.05); 2) subjects with many missing teeth had lower mean DST and BDT scores compared to subjects with few missing teeth (p < 0.05); 3) the association of PI with DST and BDT scores was dependant on the number of missing teeth (interaction: p = 0.03 and p = 0.06); and 4) education and previous cognitive scores (age 50) were important covariates. Subjects with PI had significantly lower adjusted mean DST scores compared to subjects without PI. However for adjusted BDT, the significance held only for subjects with few missing teeth. No difference in the adjusted DST and BDT scores was seen between subjects with many missing teeth compared to those with few missing teeth. These results support the hypothesis that PI may affect cognition.
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BACKGROUND:Periodontal disease is an inflammatory, dysbiotic condition. Studies have shown that in the elderly, periodontal disease was associated with cognitive dysfunction and Alzheimer's disease. OBJECTIVE:To investigate whether young healthy subjects with periodontal disease have lower cognition compared to those without periodontal disease. The salivary cytokines (IL-1β, TNF-α) levels in relation to cognition were also tested. METHODS:In a monocenter, cross-sectional study, forty subjects [mean age (SD) = 34 (5) and 48% female] from western Romania were classified into periodontal disease conditions using radiographic assessment: 10 subjects had aggressive periodontitis (AGG_P), 20 chronic mild-moderate periodontitis (CR_P), and 10 no periodontitis (NL_P). Neuropsychological assessment performed by standardized neurologists and psychologist included Rey Auditory Verbal Learning Test (RAVLT), Montreal Cognitive Assessment test (MOCA), Mini-Mental State Examination (MMSE), and Prague tests. Salivary cytokines levels were determined by ELISA. RESULTS:RAVLT and MOCA delayed recall scores were lower in AGG_P group compared to NL_P and CR_P. The learning curve was also different with subjects with AGG_P showing reduced learning performance. Contrary to our hypothesis, salivary IL-1β associated with immediate but not delayed cognitive scores. CONCLUSIONS:These results showed for the first time that subjects with AGG_P had cognitive dysfunction and IL-1β may play a role in this process.

The number of people with HIV (PWH) aged 50 years or older continues to steadily increase. The convergence of age- and HIV-related complications in these individuals presents a challenge for both patients and clinicians alike. New findings continue to emerge, as numerous researchers evaluate the combined impact of these two factors on quality of life, physiological systems, and mental health in PWH. Since its first occurrence in 2009, the International Workshop on HIV and Aging has served as a multidisciplinary meeting to share basic biomedical data, clinical trial results, treatment strategies, and epidemiological recommendations, toward better understanding and outcomes among like-minded scientific professionals. In this article, we share a selection of key findings presented in plenary talks at the 11th Annual International Workshop on HIV and Aging, held virtually from September 30, 2020 to October 2, 2020. We will also address the future directions of HIV and aging research, to further assess how the aging process intersects with chronic HIV.