Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

COMT Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial.

Propranolol is a nonselective ß-adrenergic receptor antagonist that is efficacious in reducing facial pain. There is evidence that its analgesic efficacy might be modified by variants of the catechol-O-methyltransferase (COMT) gene. We tested the hypothesis in a subset of 143 non-Hispanic Whites from a randomized controlled trial of patients with painful temporomandibular disorder (TMD). Patients were genotyped for rs4680, a single nucleotide polymorphism of COMT, and randomly allocated to either propranolol 60 mg twice daily or placebo. During the 9-wk follow-up period, patients recorded daily ratings of facial pain intensity and duration; the product was computed as an index of facial pain. Postbaseline change in the index at week 9 (the primary endpoint) was analyzed as a continuous variable and dichotomized at thresholds of ≥30% and ≥50% reduction. Mixed models for repeated measures tested for the genotype × treatment group interaction and estimated means, odds ratios (ORs), and 95% confidence limits (95% CLs) of efficacy within COMT genotypes assuming an additive genetic model. In secondary analysis, the cumulative response curves were plotted for dichotomized reductions ranging from ≥20% to ≥70%, and genotype differences in area under the curve percentages (%AUC) were calculated to signify efficacy. Mean index reduction did not differ significantly (P = 0.277) according to genotype, whereas the dichotomized ≥30% reduction revealed greater efficacy among G:G homozygotes (OR = 10.9, 95%CL = 2.4, 50.7) than among A:A homozygotes (OR = 0.8, 95%CL = 0.2, 3.2) with statistically significant interaction (P = 0.035). Cumulative response curves confirmed greater (P = 0.003) efficacy for G:G homozygotes (%AUC difference = 43.7, 95%CL = 15.4, 72.1) than for A:A homozygotes (%AUC difference = 6.5, 95%CL = -30.2, 43.2). The observed antagonistic effect of the A allele on propranolol's efficacy was opposite the synergistic effect hypothesized a priori. This unexpected result highlights the need for better knowledge of COMT's role in pain pathogenesis if the gene is to be used for precision-medicine treatment of TMD (ClinicalTrials.gov NCT02437383).

Emulation of Community Water Fluoridation Coverage Across US Counties.

INTRODUCTION: Expansion of community water fluoridation has stalled in the United States, leaving 115 million Americans without fluoridated drinking water. OBJECTIVE: This study used spatial regression methods to assess contributions of supply-side factors (neighboring counties' fluoridation coverage) and demand-side factors (health literacy, education, and population density of the local county) in predicting the extent of fluoridation in US counties. METHODS: For this cross-sectional ecological analysis, data from the 2014 Water Fluoridation Reporting System for all 3,135 US counties were merged with sociodemographic data from the 2014 American Community Survey and county-level estimates of health literacy based on the National Association of Adult Literacy Survey. We employed multilevel geographically weighted autoregressive models to predict fluoridation coverage of each county as a function of fluoridation coverage of neighboring counties and local-county covariates: either health literacy or sociodemographic characteristics. Akaike's Information Criterion was used to distinguish the better model in terms of explanatory power and parsimony. RESULTS: In the best-fit model, an increase from the first to third quartile of neighboring counties' fluoridation coverage was associated with an increase of 27.76 percentage points (95% confidence limits [CI] = 27.71, 27.81) in a local county's fluoridation coverage, while an increase from the first to third quartile of local county's health literacy was associated with an increase of 2.8 percentage points (95% CL = 2.68, 2.89). The results are consistent with a process of emulation, in which counties implement fluoridation based upon their population's health literacy and the extent of fluoridation practiced in neighboring counties. CONCLUSION: These results suggest that demand for community water fluoridation will increase as health literacy increases within a county. Furthermore, when considering expansion of fluoridation, non-fluoridated communities can benefit from precedents from nearby communities that are fluoridated. KNOWLEDGE TRANSFER STATEMENT: Expanded coverage of community water fluoridation has stalled in the United States. The economic theory of diffusion describes how, over time and space, policy enacted in one community can influence public opinion in a neighboring community. This study applies geospatial analysis of county-level data and the theory of policy diffusion to demonstrate that fluoridated counties can promote the implementation of community water fluoridation in their neighboring, non-fluoridated communities.

Long-chain omega-3 fatty acids and headache in the U.S. population.

The objective of this study was to assess whether dietary intake of long-chain omega-3 polyunsaturated fatty acids (PUFAs) is associated with lower prevalence of headache in the U.S. POPULATION: This cross-sectional study used data for a nationally representative sample of 12,317 men and women aged ≥ 20 years participating in the National Health and Nutrition Examination Surveys of 1999-2004. Interviewers recorded self-report of severe headache or migraine in the past three months. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were quantified from 24-hour dietary recall using the U.S. Department of Agriculture National Nutrient Database. Serum concentration of C-reactive protein, a marker of inflammation and potential mediator of PUFA's analgesic properties, was quantified by latex-enhanced nephelometry. Multivariable generalized linear models estimated prevalence ratios (PR) with 95% confidence limits (CL) for severe headache or migraine adjusting for NHANES cycle, sociodemographic characteristics, body mass index and total energy intake. The unadjusted prevalence of severe headache or migraine was 22.0% (females 28.2%, males 15.5%). In multivariable analysis, greater intake of omega-3 PUFAs was associated with lower prevalence of severe headache or migraine: PR 0.94 (95% CL: 0.88, 0.99, p = 0.035) per log unit increase in EPA, and PR 0.94 (95% CL: 0.90, 0.99, p = 0.023) per log unit increase in DHA. The strength of association was greater for non-Mexican Hispanics than for other racial/ethnic groups but was not attenuated after adjustment for C-reactive protein. In conclusion, higher dietary intakes of EPA and DHA were associated with lower prevalence of headache supporting the hypothesis that omega-3 PUFAs may prevent or reduce headache.

Water Fluoridation and Dental Caries in U.S. Children and Adolescents.

Fluoridation of America's drinking water was among the great public health achievements of the 20th century. Yet there is a paucity of studies from the past 3 decades investigating its dental health benefits in the U.S. POPULATION: This cross-sectional study sought to evaluate associations between availability of community water fluoridation (CWF) and dental caries experience in the U.S. child and adolescent population. County-level estimates of the percentage of population served by CWF (% CWF) from the Centers for Disease Control and Prevention's Water Fluoridation Reporting System were merged with dental examination data from 10 y of National Health and Nutrition Examination Surveys (1999 to 2004 and 2011 to 2014). Dental caries experience in the primary dentition (decayed and filled tooth surfaces [dfs]) was calculated for 7,000 children aged 2 to 8 y and in the permanent dentition (decayed, missing, and filled tooth surfaces [DMFS]) for 12,604 children and adolescents aged 6 to 17 y. Linear regression models estimated associations between % CWF and dental caries experience with adjustment for sociodemographic characteristics: age, sex, race/ethnicity, rural-urban location, head-of-household education, and period since last dental visit. Sensitivity analysis excluded counties fluoridated after 1998. In unadjusted analysis, caries experience in the primary dentition was lower in counties with ≥75% CWF (mean dfs = 3.3; 95% confidence limit [CL] = 2.8, 3.7) than in counties with <75% CWF (mean dfs = 4.6; 95% CL = 3.9, 5.4), a prevented fraction of 30% (95% CL = 11, 48). The difference was also statistically significant, although less pronounced, in the permanent dentition: mean DMFS (95% CL) was 2.2 (2.0, 2.4) and 1.9 (1.8, 2.1), respectively, representing a prevented fraction of 12% (95% CL = 1, 23). Statistically significant associations likewise were seen when % CWF was modeled as a continuum, and differences tended to increase in covariate-adjusted analysis and in sensitivity analysis. These findings confirm a substantial caries-preventive benefit of CWF for U.S. children and that the benefit is most pronounced in primary teeth.

Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study.

An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, <30%, ≥30%) with probing pocket depth (PD) ≥4 mm, and NAFLD status was determined using liver ultrasound assessment. Serum CRP levels were assayed at a central laboratory, and single-nucleotide polymorphisms previously identified through genome-wide association studies as robustly associated with serum CRP were combined into a weighted genetic CRP score (wGSCRP). Logistic regression models estimated the association between periodontitis and NAFLD within strata of serum CRP and separately within strata of the wGSCRP. The prevalence of NAFLD was 26.4% (95% confidence interval [CI], 24.6, 28.1) while 17.8% (95% CI, 16.0-19.6) had ≥30% of sites with PD ≥4 mm. Whereas the wGSCRP was not a modifier ( Pinteraction = 0.8) on the multiplicative scale, serum CRP modified the relationship between periodontitis and NAFLD ( Pinteraction = 0.01). The covariate-adjusted prevalence odds ratio of NAFLD comparing participants with ≥30% of sites with PD ≥4 mm to those with no site affected was 2.39 (95% CI, 1.32-4.31) among participants with serum CRP <1 mg/L. The corresponding estimate was 0.97 (95% CI, 0.57-1.66) for participants with serum CRP levels of 1 to 3 mg/L and 1.12 (95% CI, 0.65-1.93) for participants with serum CRP >3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.

Racial differences in periodontal disease and 10-year self-reported tooth loss among late middle-aged and older adults: the dental ARIC study.

OBJECTIVE: To investigate racial differences in the associations between periodontitis and 10-year self-reported incident tooth loss in a biracial, community-based cohort of US late middle-aged and older adults. METHODS: Subjects were 3,466 dentate men and women aged 53-74 who underwent dental examinations from 1996 to1998. In 2012-2013, telephone interviewers asked participants about tooth loss in the preceding 10 years. Separate multivariable ordinal logistic regression models were used to calculate proportional odds ratios (OR) and 95% confidence intervals (CI) as estimates of association between periodontitis and tooth loss for Whites and African-Americans (AAs). RESULTS: The majority of participants were White (85 percent) and female (57 percent) with 23 teeth on average at enrollment. Approximately half the Whites (56 percent) and AAs (49 percent) had periodontitis. At follow-up, approximately 44 percent of AAs and 38 percent of Whites reported having lost ≥1 tooth. In multivariable models, severe periodontitis (OR = 3.03; 95% CI = 2.42-3.80) and moderate periodontitis (OR = 1.64; 95% CI= 1.39-1.94) were significant risk factors of incident tooth loss among Whites. For AAs, severe but not moderate periodontitis increased the odds of incident tooth loss (OR = 2.22; 95% CI = 1.37-3.59). In the final model, education was inversely associated with incident tooth loss among AAs, while lower income was associated with greater odds of tooth loss among Whites. CONCLUSIONS: In this population-based cohort, there is racial heterogeneity in the association between periodontitis and tooth loss. Interventions to reduce the impact of periodontitis on tooth loss need to consider these differences.

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 106) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10-8) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10-8) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10-8) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10-7) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.

Periodontal therapy and glycaemic control among individuals with type 2 diabetes: reflections from the PerioCardio study.

OBJECTIVES: Diabetes mellitus and periodontal disease are highly prevalent among Indigenous Australian adults. Untreated periodontitis impacts glycaemic control in people with diabetes. The aim of this study was to report on the effect of periodontal therapy on glycaemic control among people with obesity. METHODS: This subgroup analysis is limited to 62 participants with diabetes from the original 273 Aboriginal Australian adults enrolled into the PerioCardio study. Intervention participants received full-mouth non-surgical periodontal scaling during a single, untimed session while controls were untreated. Endpoints of interest included change in glycated haemoglobin (HbA1c), C-reactive protein (CRP) and periodontal status at 3 months post-intervention. RESULTS: There were more females randomized to the treatment group (n = 17) than control (n = 10) while the control group had a higher overall body mass index (BMI) [mean (SD)] 33.1 (9.7 kg m-2 ) versus 29.9 (6.0 kg m-2 ). A greater proportion of males were followed up at 3 months compared to females, P = 0.05. Periodontal therapy did not significantly reduce HbA1c: ancova difference in means 0.22 mmol mol-1 (95% CI -6.25 to 6.69), CRP: ancova difference in means 0.64 (95% CI -1.08, 2.37) or periodontal status at 3 months. CONCLUSIONS: Non-surgical periodontal therapy did not significantly reduce glycated haemoglobin in participants with type 2 diabetes. Reasons are likely to be multifactorial and may be influenced by persistent periodontal inflammation at the follow-up appointments. Alternatively, the BMI of study participants may impact glycaemic control via alternative mechanisms involving the interplay between inflammation and adiposity meaning HbA1c may not be amenable to periodontal therapy in these individuals.

Painful Temporomandibular Disorder: Decade of Discovery from OPPERA Studies.

In 2006, the OPPERA project (Orofacial Pain: Prospective Evaluation and Risk Assessment) set out to identify risk factors for development of painful temporomandibular disorder (TMD). A decade later, this review summarizes its key findings. At 4 US study sites, OPPERA recruited and examined 3,258 community-based TMD-free adults assessing genetic and phenotypic measures of biological, psychosocial, clinical, and health status characteristics. During follow-up, 4% of participants per annum developed clinically verified TMD, although that was a "symptom iceberg" when compared with the 19% annual rate of facial pain symptoms. The most influential predictors of clinical TMD were simple checklists of comorbid health conditions and nonpainful orofacial symptoms. Self-reports of jaw parafunction were markedly stronger predictors than corresponding examiner assessments. The strongest psychosocial predictor was frequency of somatic symptoms, although not somatic reactivity. Pressure pain thresholds measured at cranial sites only weakly predicted incident TMD yet were strongly associated with chronic TMD, cross-sectionally, in OPPERA's separate case-control study. The puzzle was resolved in OPPERA's nested case-control study where repeated measures of pressure pain thresholds revealed fluctuation that coincided with TMD's onset, persistence, and recovery but did not predict its incidence. The nested case-control study likewise furnished novel evidence that deteriorating sleep quality predicted TMD incidence. Three hundred genes were investigated, implicating 6 single-nucleotide polymorphisms (SNPs) as risk factors for chronic TMD, while another 6 SNPs were associated with intermediate phenotypes for TMD. One study identified a serotonergic pathway in which multiple SNPs influenced risk of chronic TMD. Two other studies investigating gene-environment interactions found that effects of stress on pain were modified by variation in the gene encoding catechol O-methyltransferase. Lessons learned from OPPERA have verified some implicated risk factors for TMD and refuted others, redirecting our thinking. Now it is time to apply those lessons to studies investigating treatment and prevention of TMD.

Directed Acyclic Graphs for Oral Disease Research.

Directed acyclic graphs (DAGs) are nonparametric graphical tools used to depict causal relations in the epidemiologic assessment of exposure-outcome associations. Although their use in dental research was first advocated in 2002, DAGs have yet to be widely adopted in this field. DAGs help identify threats to causal inference such as confounders, bias due to subject selection, and inappropriate handling of missing data. DAGs can also inform the data analysis strategy based on relations among variables depicted on it. This article uses the example of a study of temporomandibular disorders (TMDs), investigating causal effects of facial injury on subsequent risk of TMD. We illustrate how DAGs can be used to identify 1) potential confounders, 2) mediators and the consequences of attempt to estimate direct causal effects, 3) colliders and the consequences of conditioning on colliders, and 4) variables that are simultaneously mediators and confounders and the consequences of adjustment for such variables. For example, one DAG shows that statistical adjustment for the pressure pain threshold would necessarily bias the causal relation between facial injury and TMD. Finally, we discuss the usefulness of DAGs during study design, subject selection, and choosing variables to be measured in a study.

Does lower lifetime fluoridation exposure explain why people outside capital cities have poor clinical oral health?

BACKGROUND: Australians outside state capital cities have greater caries experience than their counterparts in capital cities. We hypothesized that differing water fluoridation exposure was associated with this disparity. METHODS: Data were the 2004-06 Australian National Survey of Adult Oral Health. Examiners measured participant decayed, missing and filled teeth and DMFT Index, and lifetime fluoridation exposure was quantified. Multivariable linear regression models estimated differences in caries experience between capital city residents and others, with and without adjustment for fluoridation exposure. RESULTS: There was greater mean lifetime fluoridation exposure in state capital cities (59.1%, 95% confidence interval = 56.9, 61.4) than outside capital cities (42.3, confidence interval = 36.9, 47.6). People located outside capital city areas had differing sociodemographic characteristics and dental visiting patterns, and a higher mean DMFT (capital cities = 12.9, non-capital cities = 14.3, p = 0.02), than people from capital cities. After adjustment for sociodemographic characteristics and dental visits, DMFT of people living in capital cities was less than non-capital city residents (regression coefficient = 0.8, p = 0.01). The disparity was no longer statistically significant (regression coefficient = 0.6, p = 0.09) after additional adjustment for fluoridation exposure.

COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.

When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according to biological susceptibility. We hypothesized that temporal escalation in stress exacerbates risk for TMD, and the effect is amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT), regulating catechol neurotransmitter catabolism. We used data from the Orofacial Pain: Prospective Evaluation and Risk Assessment prospective cohort study of 2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS) measured psychological stress. Genotyped DNA from blood samples determined COMT diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner-verified incident TMD. PSS scores at baseline were 20% greater (P < 0.001) in adults who developed incident TMD compared with TMD-free controls. Baseline PSS scores increased by 9% (P = 0.003) during follow-up in cases but remained stable in controls. This stress escalation was limited to incident cases with COMT diplotypes coding for low-activity COMT, signifying impaired catabolism of catecholamines. Cox regression models confirmed significant effects on TMD hazard of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a significant (P = 0.04) interaction of COMT diplotype and time-varying stress showed that a postbaseline increase of 1.0 standard deviation in PSS more than doubled risk of TMD incidence in subjects with low-activity COMT diplotypes (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence limits: 0.96, 2.09). Findings provide novel insights into dynamic effects of psychological stress on TMD pain, highlighting that effects are most pronounced in individuals whose genetic susceptibility increases responsiveness to catecholamine neurotransmitters.

The effect of lifetime fluoridation exposure on dental caries experience of younger rural adults.

BACKGROUND: The aim of this study was to confirm whether the level of lifetime fluoridation exposure is associated with lower dental caries experience in younger adults (15-46 years). METHODS: Data of the cohort born between 1960 and 1990 residing outside Australia's capital cities from the 2004-2006 Australian National Survey of Adult Oral Health were analysed. Residential history questionnaires were used to determine the percentage of each person's lifetime exposure to fluoridated water (<50%/50+%). Examiners recorded decayed, missing and filled permanent teeth (DMFT). Socio-demographic variables, periodontal risk factors, and access to dental care were included in multivariable least-squares regression models. RESULTS: In bivariate analysis, the higher level of fluoridation category had significantly lower DMFT (mean 6.01 [SE=0.62]) than the lower level of fluoridation group (9.14 [SE=0.73] p<0.01) and lower numbers of filled teeth (4.08 [SE=0.43], 7.06 [SE=0.62], p<0.01). In multivariate analysis, the higher number of full-time equivalent dentists per 100,000 people was associated with a lower mean number of missing teeth (regression coefficient estimate=-1.75, p=0.03), and the higher level of water fluoridation with a lower mean DMFT (-2.45, p<0.01) and mean number of filled teeth (-2.52, p<0.01). CONCLUSIONS: The higher level of lifetime fluoridation exposure was associated with substantially lower caries experience in younger rural adults, largely due to a lower number of filled teeth.

Projections of U.S. Edentulism prevalence following 5 decades of decline.

After decades of decline in prevalence of complete tooth loss (edentulism), the trend continues to be misinterpreted, producing flawed projections and misdirected health goals. We investigated population trends in edentulism among U.S. adults aged ≥ 15 yr by creating time-series data from 5 national cross-sectional health surveys: 1957-1958 (n ≈ 100,000 adults), 1971-1975 (n = 14,655 adults), 1988-1998 (n = 18,011 adults), 1999-2002 (n = 12,336 adults), and 2009-2012 (n = 10,522 adults). Birth cohort analysis was used to isolate age and cohort effects. Geographic and sociodemographic variation in prevalence was investigated with a sixth U.S. survey of 432,519 adults conducted in 2010. Prevalence through 2050 was projected with age-cohort regression models using Monte-Carlo simulation of prediction intervals. Across the 5-decade observation period, edentulism prevalence declined from 18.9% in 1957-1958 (95% confidence limits: 18.4%, 19.4%) to 4.9% in 2009-2012 (95% confidence limits: 4.0%, 5.8%). The most influential determinant of the decline was the passing of generations born before the 1940s, whose rate of edentulism incidence (5%-6% per decade of age) far exceeded later cohorts (1%-3% per decade of age). High-income households experienced a greater relative decline, although a smaller absolute decline, than low-income households. By 2010, edentulism was a rare condition in high-income households, and it had contracted geographically to states with disproportionately high poverty. With the passing of generations born in the mid-20th century, the rate of decline in edentulism is projected to slow, reaching 2.6% (95% prediction limits: 2.1%, 3.1%) by 2050. The continuing decline will be offset only partially by population growth and population aging such that the predicted number of edentulous people in 2050 (8.6 million; 95% prediction limits: 6.8 million, 10.3 million) will be 30% lower than the 12.2 million edentulous people in 2010.

Self-reported measures for surveillance of periodontitis.

The purpose of this study was to evaluate the performance of self-reported measures in predicting periodontitis in a representative US adult population, based on 2009-2010 National Health and Nutrition Examination Survey (NHANES) data. Self-reported gum health and treatment history, loose teeth, bone loss around teeth, tooth not looking right, and use of dental floss and mouthwash were obtained during in-home interviews and validated against full-mouth clinically assessed periodontitis in 3,743 US adults 30 years and older. All self-reported measures (> 95% item response rates) were associated with periodontitis, and bivariate correlations between responses to these questions were weak, indicating low redundancy. In multivariable logistic regression modeling, the combined effects of demographic measures and responses to 5 self-reported questions in predicting periodontitis of mild or greater severity were 85% sensitive and 58% specific and produced an 'area under the receiver operator characteristic curve' (AUROCC) of 0.81. Four questions were 95% sensitive and 30% specific, with an AUROCC of 0.82 in predicting prevalence of clinical attachment loss ≥ 3 mm at one or more sites. In conclusion, self-reported measures performed well in predicting periodontitis in US adults. Where preferred clinically based surveillance is unattainable, locally adapted variations of these self-reported measures may be a promising alternative for surveillance of periodontitis.

Cognitive decline and oral health in middle-aged adults in the ARIC study.

Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as 'studentized' residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases.

Sleep apnea symptoms and risk of temporomandibular disorder: OPPERA cohort.

The authors tested the hypothesis that obstructive sleep apnea (OSA) signs/symptoms are associated with the occurrence of temporomandibular disorder (TMD), using the OPPERA prospective cohort study of adults aged 18 to 44 years at enrollment (n = 2,604) and the OPPERA case-control study of chronic TMD (n = 1,716). In both the OPPERA cohort and case-control studies, TMD was examiner determined according to established research diagnostic criteria. People were considered to have high likelihood of OSA if they reported a history of sleep apnea or ≥ 2 hallmarks of OSA: loud snoring, daytime sleepiness, witnessed apnea, and hypertension. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence limits (CL) for first-onset TMD. Logistic regression estimated odds ratios (OR) and 95% CL for chronic TMD. In the cohort, 248 individuals developed first-onset TMD during the median 2.8-year follow-up. High likelihood of OSA was associated with greater incidence of first-onset TMD (adjusted HR = 1.73; 95% CL, 1.14, 2.62). In the case-control study, high likelihood of OSA was associated with higher odds of chronic TMD (adjusted OR = 3.63; 95% CL, 2.03, 6.52). Both studies supported a significant association of OSA symptoms and TMD, with prospective cohort evidence finding that OSA symptoms preceded first-onset TMD.

Effects of fluoridated drinking water on dental caries in Australian adults.

Systematic reviews produce conflicting conclusions regarding dental caries-preventive effects of water fluoridation in adults. The authors investigated the relationship using data from the nationally representative 2004-2006 Australian National Survey of Adult Oral Health. Effects were compared between the pre-fluoridation cohort born before 1960 (n = 2,270) and the cohort born between 1960 and 1990 (n = 1,509), when widespread implementation of fluoridation increased population coverage from < 1% to 67%. Residential history questionnaires determined the percentage of each person's lifetime exposed to fluoridated water. Examiners recorded decayed, missing, and filled teeth (DMF-Teeth) and decayed and filled tooth surfaces (DF-Surfaces). Socio-demographic and preventive dental behaviors were included in multivariable least-squares regression models adjusted for potential confounding. In fully adjusted models, > 75% of lifetime exposure to fluoridation relative to < 25% of lifetime exposure was associated with 11% and 10% fewer DMF-Teeth in the pre-1960 (p < .0001) and 1960-1990 cohorts (p = .018), respectively. Corresponding reductions in DF-Surfaces were 30% (p < .001) and 21% (p < .001). Findings for intermediate fluoridation exposure suggested a dose-response relationship. Results were consistent in sensitivity analyses accounting for missing data. In this nationally representative sample of Australian adults, caries-preventive effects of water fluoridation were at least as great in adults born before widespread implementation of fluoridation as after widespread implementation of fluoridation.