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Evidence-based Dentistry Jun 2024This study aimed at determining the association between periodontitis and mild cognitive impairment. For this, different electronic databases, including PubMed, Scopus,... (Meta-Analysis)
Meta-Analysis
DATA SOURCES
This study aimed at determining the association between periodontitis and mild cognitive impairment. For this, different electronic databases, including PubMed, Scopus, Embase and Web of Science, were searched for finding the relevant literature. In addition, hand searching of relevant journals was also done to find gray literature.
STUDY SELECTION
The systematic review included observational studies only. Accordingly, case-control, cohort and cross-sectional studies were searched. The search strategy was based on PECO framework, wherein the studies which included patients with/without periodontitis and patients with/without mild cognitive impairment (MCI) were included.
DATA EXTRACTION AND SYNTHESIS
A total of 7 studies were included and the data from these studies and the data including bibliographic details, demographic data, data about periodontitis, presence of MCI etc. was extracted from the included articles. The extracted data, was then assessed for heterogeneity using clinical parameters and I statistical test. Owing to low heterogeneity, fixed-effects model was used for meta-analysis.
RESULTS
Meta-analysis was done to determine the association between periodontitis and MCI and significantly higher incidence of MCI was found in patients with periodontitis OR = OR, 1.70 (95% CI: 1.24-2.32, p < 0.001). A subgroup analysis was done by including the studies comparing incidence of MCI in patients with severe periodontitis, which resulted in even stronger association with an OR of 2.09 (95% CI: 1.49-2.92, p < 0.001). Lastly, periodontal parameters, including CAL, PPD, and PI were compared amongst patients with/without MCI. Significant differences were observed for both CAL and PI, with worsening of values in patients with MCI. Observed mean difference for CAL and PI were 0.44 (95% CI: 0.12-0.75) and 0.72 (95% CI:0.50-0.93), respectively. NS differences were observed for PPD values with a mean difference of 0.21 and 95% CI as -0.08 to 0.49.
CONCLUSIONS
Strong association between periodontitis and MCI was observed, indicating periodontitis to be a risk factor for MCI.
Topics: Humans; Cognitive Dysfunction; Periodontitis; Risk Factors; Incidence
PubMed: 38724750
DOI: 10.1038/s41432-024-01015-5 -
Neurology Sep 2023Although tooth loss and periodontitis have been considered risk factors of Alzheimer disease, recent longitudinal researches have not found a significant association...
BACKGROUND AND OBJECTIVES
Although tooth loss and periodontitis have been considered risk factors of Alzheimer disease, recent longitudinal researches have not found a significant association with hippocampal atrophy. Therefore, this study aimed to clarify a longitudinal association between the number of teeth present (NTP) and hippocampal atrophy dependent on the severity of periodontitis in a late middle-aged and older adult population.
METHODS
This study included community-dwelling individuals aged 55 years or older who had no cognitive decline and had undergone brain MRI and oral and systemic data collection twice at 4-year intervals. Hippocampal volumes were obtained from MRIs by automated region-of-interest analysis. The mean periodontal probing depth (PD) was used as a measure of periodontitis. Multiple regression analysis was performed with the annual symmetric percentage change (SPC) of the hippocampal volume as the dependent variable and including an interaction term between NTP and mean PD as the independent variable. The interaction details were examined using the Johnson-Neyman technique and simple slope analysis. The 3-way interaction of NTP, mean PD, and time on hippocampal volume was analyzed using a linear mixed-effects model, and the interaction of NTP and time was examined in subgroups divided by the median mean PD. In all models, dropout bias was adjusted by inverse probability weighting.
RESULTS
Data of 172 participants were analyzed. The qualitative interaction between NTP and the mean PD was significant for the annual SPC in the left hippocampus. The regression coefficient of the NTP on the annual SPC in the left hippocampus was positive ( = 0.038, = 0.026) at the low-level mean PD (mean -1 SD) and negative ( = -0.054, = 0.001) at the high-level mean PD (mean +1 SD). Similar results were obtained in the linear mixed-effects model; the interaction of NTP and time was significant in the higher mean PD group.
DISCUSSION
In a late middle-aged and older cohort, fewer teeth were associated with a faster rate of left hippocampal atrophy in patients with mild periodontitis, whereas having more teeth was associated with a faster rate of atrophy in those with severe periodontitis. The importance of keeping teeth healthy is suggested.
Topics: Middle Aged; Humans; Aged; Independent Living; Alzheimer Disease; Hippocampus; Magnetic Resonance Imaging; Periodontitis; Atrophy; Longitudinal Studies
PubMed: 37407259
DOI: 10.1212/WNL.0000000000207579 -
Obesity Facts 2024It is controversial whether obesity and periodontitis are related. A representative US population was examined for the relationship between obesity and periodontitis.
INTRODUCTION
It is controversial whether obesity and periodontitis are related. A representative US population was examined for the relationship between obesity and periodontitis.
METHODS
In the National Health and Nutrition Examination Survey (NHANES) 2011-2014, participants (n = 6,662) aged 30 years or older and who underwent periodontal examinations were chosen for analysis. An assessment of obesity was based on body mass index (BMI) and waist circumference (WC). Estimates of obesity and periodontal disease were made using univariate and multivariate logistic regression models.
RESULTS
According to an adjusted odds ratio (OR) for periodontitis, BMI (OR = 1.01, 95% CI: 1.01∼1.02) and WC (OR = 1.01, 95% CI: 1∼1.01) were significantly associated with periodontitis, respectively. After adjusting for confounding factors, the OR for patients with high WC with periodontitis was 1.18 (1.04∼1.33) compared to normal WC. BMI and WC subgroups showed no significant interaction (p for interaction >0.05), except for the age interaction in BMI. Among young adults aged 30-44 years, obesity was significantly associated with periodontitis in subgroups; the adjusted OR for having periodontal disease was 1.02 (1∼1.03) and 1.01 (1∼1.02) for subjects with BMI and WC, respectively. When all covariates were adjusted, BMI ≥30 kg/m2 was statistically significantly associated with prevalence of periodontal disease among people aged 30-44 years (p < 0.001).
CONCLUSIONS
BMI and WC are significantly associated with periodontitis, even after adjusting for many variables, and were equally significant in obese (BMI ≥30 kg/m2) young people (30-44 years).
Topics: Young Adult; Humans; Adolescent; Nutrition Surveys; Obesity; Body Mass Index; Periodontitis; Periodontal Diseases; Waist Circumference; Risk Factors
PubMed: 37935140
DOI: 10.1159/000534751 -
Advanced Healthcare Materials Nov 2023Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains...
Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell-based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene-related peptide (CGRP)-loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP can effectively ameliorate the inflammation-induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3)/Caspase-1 (CASP1) pathway. Moreover, the porous architecture of PMs provides effective cell-carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC-loaded PMs can effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell-mediated tissue regeneration and repair under inflammatory conditions.
Topics: Humans; Calcitonin Gene-Related Peptide; Microspheres; Porosity; Bone Regeneration; Periodontitis; Osteogenesis; Mesenchymal Stem Cells; Inflammation; Cell Differentiation
PubMed: 37515813
DOI: 10.1002/adhm.202301366 -
Australian Dental Journal Dec 2023Patients with periodontitis often require an inter-disciplinary approach, including orthodontic treatment, for effective rehabilitation of masticatory function,... (Review)
Review
Patients with periodontitis often require an inter-disciplinary approach, including orthodontic treatment, for effective rehabilitation of masticatory function, aesthetics and quality of life. The aim of this narrative review was to comprehensively discuss literature focusing on the biology, indications and inter-disciplinary connections related to the orthodontic approach in patients with periodontitis and to present clinical concepts in accordance with valid guidelines. The outcomes of the experimental studies indicate that orthodontic tooth movement (OTM) can be performed safely for teeth with reduced periodontium, provided infection and inflammation are controlled. Orthodontic treatment can correct pathological tooth migration, is not associated with deterioration of clinical periodontal parameters and improves aesthetics. Intrusion is safe when performed with light forces and under a strict oral hygiene regimen. Teeth can be moved either towards or away from the intrabony defect previously subjected to regenerative procedures, and research suggests that OTM has the potential to enhance bone formation after regenerative therapy. The data on orthodontic movement of teeth with furcation involvement are very scarce. The improvement in furcation involvement following either combined periodontal and orthodontic treatment was only documented in animal model studies. Due to bone and tooth loss, special consideration should be given to orthodontic treatment mechanics. © 2023 Australian Dental Association.
Topics: Animals; Humans; Quality of Life; Australia; Periodontitis; Periodontium; Osteogenesis; Tooth Movement Techniques
PubMed: 37688346
DOI: 10.1111/adj.12974 -
International Journal of Molecular... Apr 2024The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality... (Review)
Review
The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer's disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson's disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as . Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged.
Topics: Humans; Periodontitis; Risk Factors; Neurodegenerative Diseases; Parkinson Disease; Alzheimer Disease
PubMed: 38674088
DOI: 10.3390/ijms25084504 -
International Journal of Molecular... Sep 2023Periodontitis is one of the primary causes of tooth loss, and is also related to various systemic diseases. Early detection of this condition is crucial when it comes to... (Meta-Analysis)
Meta-Analysis Review
Periodontitis is one of the primary causes of tooth loss, and is also related to various systemic diseases. Early detection of this condition is crucial when it comes to preventing further oral damage and the associated health complications. This study offers a systematic review of the literature published up to April 2023, and aims to clearly explain the role of proteomics in identifying salivary biomarkers for periodontitis. Comprehensive searches were conducted on PubMed and Web of Science to shortlist pertinent studies. The inclusion criterion was those that reported on mass spectrometry-driven proteomic analyses of saliva samples from periodontitis cohorts, while those on gingivitis or other oral diseases were excluded. An assessment for risk of bias was carried out using the Newcastle-Ottawa Scale and Quality Assessment of Diagnostic Accuracy Studies or the NIH quality assessment tool, and a meta-analysis was performed for replicable candidate biomarkers, i.e., consistently reported candidate biomarkers (in specific saliva samples, and periodontitis subgroups, reported in ≥2 independent cohorts/reports) were identified. A Gene Ontology enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resources, which consistently expressed candidate biomarkers, to explore the predominant pathway wherein salivary biomarkers consistently manifested. Of the 15 studies included, 13 were case-control studies targeting diagnostic biomarkers for periodontitis participants (periodontally healthy/diseased, = 342/432), while two focused on biomarkers responsive to periodontal treatment ( = 26 participants). The case-control studies were considered to have a low risk of bias, while the periodontitis treatment studies were deemed fair. Summary estimate and confidence/credible interval, etc. determination for the identified putative salivary biomarkers could not be ascertained due to the low number of studies in each case. The results from the included case-control studies identified nine consistently expressed candidate biomarkers (from nine studies with 230/297 periodontally healthy/diseased participants): (i) those that were upregulated: alpha-amylase, serum albumin, complement C3, neutrophil defensin, profilin-1, and S100-P; and (ii) those that were downregulated: carbonic anhydrase 6, immunoglobulin J chain, and lactoferrin. All putative biomarkers exhibited consistent regulation patterns. The implications of the current putative marker proteins identified were reviewed, with a focus on their potential roles in periodontitis diagnosis and pathogenesis, and as putative therapeutic targets. Although in its early stages, mass spectrometry-based salivary periodontal disease biomarker proteomics detection appeared promising. More mass spectrometry-based proteomics studies, with or without the aid of already available clinical biochemical approaches, are warranted to aid the discovery, identification, and validation of periodontal health/disease indicator molecule(s). Protocol registration number: CRD42023447722; supported by RD-02-202410 and GRF17119917.
Topics: Humans; Proteomics; Periodontitis; Mass Spectrometry; Biomarkers; Proteins; Periodontal Diseases; Saliva
PubMed: 37834046
DOI: 10.3390/ijms241914599 -
Annals of the New York Academy of... Nov 2023The gut microbiota is a bridge linking periodontitis and systemic diseases, such as diabetes mellitus (DM). The probiotic Clostridium butyricum MIYAIRI 588 (CBM588) is...
The gut microbiota is a bridge linking periodontitis and systemic diseases, such as diabetes mellitus (DM). The probiotic Clostridium butyricum MIYAIRI 588 (CBM588) is reportedly an effective therapeutic approach for gut dysbiosis. Here, in a mouse model, we explored the therapeutic effect of CBM588 on periodontal bone destruction in DM and DM-associated periodontitis (DMP), as well as the underlying mechanism. Micro-computed tomography revealed that DM and DMP both aggravated periodontal bone destruction, which was alleviated by intragastric supplementation with CBM588. Moreover, 16S rRNA sequencing and untargeted metabolite analysis indicated that CBM588 ameliorated DMP-triggered dysbiosis and led to reduced oxidative stress associated with elevated 4-hydroxybenzenemethanol (4-HBA) in serum. Furthermore, in vitro and in vivo experiments found that the metabolite 4-HBA promoted nuclear factor erythroid 2-related factor 2 (Nrf2) signaling activation and modulated the polarization of macrophages, thus ameliorating inflammatory bone destruction in DMP. Our study demonstrates the protective effects of CBM588 in DM-induced mice, with and without ligature-induced periodontitis. The mechanism involves regulation of the gut microbiota and restoration of the integrity of the gut barrier to alleviate oxidative damage by elevating serum 4-HBA. This study suggests the possibility of CBM588 as a therapeutic adjuvant for periodontal treatment in diabetes patients.
Topics: Humans; Mice; Animals; Clostridium butyricum; Alveolar Bone Loss; X-Ray Microtomography; RNA, Ribosomal, 16S; Dysbiosis; Periodontitis; Diabetes Mellitus
PubMed: 37658670
DOI: 10.1111/nyas.15058 -
Journal of Cellular and Molecular... Nov 2023Periodontal bone regeneration is a major challenge in the treatment of periodontitis. However, the regenerative vitality of periodontal ligament cells (PDLCs) declines...
Periodontal bone regeneration is a major challenge in the treatment of periodontitis. However, the regenerative vitality of periodontal ligament cells (PDLCs) declines in the environment of periodontitis and accompanying oxidative stress. This study aimed to investigate the functional mechanisms of Bach1, a transcriptional suppressor involved in oxidative stress response, and its regulation of PDLC osteogenesis under inflammatory conditions. We observed a significant elevation in Bach1 expression in periodontal tissues with periodontitis and PDLCs under inflammatory conditions. Knockdown of Bach1 alleviated the inflammation-induced oxidative stress level and partly offset the inhibitory effect of inflammatory conditions on osteogenesis, as well as the expression of osteogenic genes BMP6, OPG and RUNX2. Similarly, knockdown of Bach1 protects PDLCs from inflammatory damage to periodontal bone regeneration in vivo. Furthermore, we found that Bach1 could bind to the histone methyltransferase EZH2, and the binding increased under inflammatory conditions. Bach1 enhanced the ability of EZH2 to catalyse H3K27me3 on the promoter region of RUNX2 and BMP6, thus repressing the expression of osteoblastic genes. In conclusion, our study revealed that knockdown of Bach1 effectively rescued the osteogenesis and oxidative stress of PDLCs with inflammation. Bach1 could be a promising target for enhancing periodontal tissue regeneration under periodontitis conditions.
Topics: Humans; Bone Regeneration; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Inflammation; Osteogenesis; Periodontal Ligament; Periodontitis
PubMed: 37602966
DOI: 10.1111/jcmm.17916 -
Journal of Dental Research Jun 2024Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of...
Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the intricate involvement of macrophage-mediated inflammation in the pathogenesis of periodontitis under both normal and T2DM conditions. However, the underlying mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein featuring an MHC-I domain, has been implicated in both inflammation and metabolic disorders. In this study, we found that AZGP1 was primarily colocalized with macrophages in periodontitis tissues. AZGP1 was increased in periodontitis compared with controls, which was further elevated when accompanied by T2DM. Adeno-associated virus-mediated overexpression of in the periodontium significantly enhanced periodontal inflammation and alveolar bone loss, accompanied by elevated M1 macrophages and pyroptosis in murine models of periodontitis and T2DM-associated periodontitis, while mice exhibited opposite effects. In primary bone marrow-derived macrophages stimulated by lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or knockout of markedly upregulated or suppressed, respectively, the expression of macrophage M1 markers and key components of the NLR Family Pyrin Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium from -overexpressed macrophages under LPS or LPS+PA stimulation induced higher inflammatory activation and lower osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization and pyroptosis in macrophages and associated detrimental effects on hPDLSCs induced by overexpression could be rescued by NLRP3 or caspase-1 inhibition. Collectively, our study elucidated that AZGP1 could aggravate periodontitis by promoting macrophage M1 polarization and pyroptosis through the NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. This finding deepens the understanding of AZGP1 in the pathogenesis of periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects of diabetes on periodontal inflammation.
Topics: Pyroptosis; Animals; Macrophages; Periodontitis; Mice; Humans; Diabetes Mellitus, Type 2; NLR Family, Pyrin Domain-Containing 3 Protein; Disease Models, Animal; Mice, Inbred C57BL; Caspase 1; Male; Mice, Knockout; Signal Transduction; Alveolar Bone Loss; Glycoproteins
PubMed: 38491721
DOI: 10.1177/00220345241235616