Faculty Bibliography

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.

Introduction/UNASSIGNED:Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome. Methods/UNASSIGNED:A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect-size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups. Results/UNASSIGNED: = 0.02 and 0.01) but not with P-tau. Discussion/UNASSIGNED:We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aβ.

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

OBJECTIVE:Both diabetes mellitus (DM) and poor oral health are common chronic conditions and risk factors of Alzheimer's disease and related dementia among older adults. This study assessed the effects of DM and complete tooth loss (TL) on cognitive function, accounting for their interactions. METHODS:Longitudinal data were obtained from the 2006, 2012, and 2018 waves of the Health and Retirement Study. This cohort study included 7,805 respondents aged 65 years or older with 18,331 person-year observations. DM and complete TL were self-reported. Cognitive function was measured by the Telephone Interview for Cognitive Status. Random-effect regressions were used to test the associations, overall and stratified by sex. RESULTS:Compared with older adults without neither DM nor complete TL, those with both conditions (b = -1.35, 95% confidence interval [CI]: -1.68, -1.02), with complete TL alone (b = -0.67, 95% CI: -0.88, -0.45), or with DM alone (b = -0.40, 95% CI: -0.59, -0.22), had lower cognitive scores. The impact of having both conditions was significantly greater than that of having DM alone (p < .001) or complete TL alone (p = 0.001). Sex-stratified analyses showed the effects were similar in males and females, except having DM alone was not significant in males. CONCLUSION/CONCLUSIONS:The co-occurrence of DM and complete TL poses an additive risk for cognition. Healthcare and family-care providers should pay attention to the cognitive health of patients with both DM and complete TL. Continued efforts are needed to improve older adults' access to dental care, especially for individuals with DM.

There is currently no criterion to select appropriate bioinformatics tools and reference databases for analysis of 16S rRNA amplicon data in the human oral microbiome. Our study aims to determine the influence of multiple tools and reference databases on α-diversity measurements and β-diversity comparisons analyzing the human oral microbiome. We compared the results of taxonomical classification by Greengenes, the Human Oral Microbiome Database (HOMD), National Center for Biotechnology Information (NCBI) 16S, SILVA, and the Ribosomal Database Project (RDP) using Quantitative Insights Into Microbial Ecology (QIIME) and the Divisive Amplicon Denoising Algorithm (DADA2). There were 15 phyla present in all of the analyses, four phyla exclusive to certain databases, and different numbers of genera were identified in each database. Common genera found in the oral microbiome, such as Veillonella, Rothia, and Prevotella, are annotated by all databases; however, less common genera, such as Bulleidia and Paludibacter, are only annotated by large databases, such as Greengenes. Our results indicate that using different reference databases in 16S rRNA amplicon data analysis could lead to different taxonomic compositions, especially at genus level. There are a variety of databases available, but there are no defined criteria for data curation and validation of annotations, which can affect the accuracy and reproducibility of results, making it difficult to compare data across studies.

Approximately 47 million people worldwide have been diagnosed with dementia, 60%-80% of whom have dementia of the Alzheimer's disease type. Unfortunately, there is no cure in sight. Defining modifiable risk factors for Alzheimer's disease may have a significant impact on its prevalence. An increasing body of evidence suggests that chronic inflammation and microbial dysbiosis are risk factors for Alzheimer's disease. Periodontal disease is a chronic inflammatory disease that develops in response to response to microbial dysbiosis. Many studies have shown an association between periodontal disease and Alzheimer's disease. The intent of this paper was to review the existing literature and determine, using the Bradford Hill criteria, whether periodontal disease is causally related to Alzheimer's disease.

The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1β were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection.