Background:Social support is an important psychosocial resource that can facilitate engaging in healthy behaviors, including oral health behaviors. Nine scales assessing Oral Health Behavior Social Support (OHBSS) for brushing, flossing and seeking dental care were developed and validated in the English and Spanish languages. The full-length scales included 37 required items to assess social support from three sources: family, health providers, and others/friends. The OHBSS-SF scales cover three oral health behaviors, use six items each to assess social support for brushing, flossing and dental care, and retain the nine-scale structure. Response options range from one (never) to four (always), with higher scores reflecting more frequent receipt of social support. This paper describes the item reduction process/outcomes and presents model fit indices and psychometric properties of the 17-item OHBSS-Short Form (OHBSS-SF) scales. Methods:A large Mexican-American young adult sample completed an online survey in English or Spanish (N=502). Participants completed the OHBSS-SF along with several other validated scales assessing general social support, dental fear, and acculturation. The survey also queried oral health behaviors of interest and socio-demographic characteristics. A subset of participants (n=56) also completed the OHBSS-SF items a second time two to six weeks later to assess test-retest reliability. Model fit indices and psychometric properties for each of the nine OHBSS-SF scales were calculated for the full sample and subgroups stratified by the three study design characteristics of language (English/Spanish), sex (male/female), and marital status (single/married). Results:The OHBSS-SF scales correlated very highly with the full-length versions (r=0.95-0.98), and all OHBSS-SF scales exhibited acceptable model fit indices. The OHBSS-SF demonstrated stability in the full sample and in Spanish, with good to excellent intra-class correlations, supporting test-retest reliability. Patterns of moderate correlations supported convergent validity with validated general social support measures. Patterns of weak correlations suggested divergent validity between OHBSS-SF and other non-social support measures. Conclusions:The OHBSS-SF demonstrated acceptable psychometric properties. A few significant differences by subgroup characteristics were identified. The OHBSS-SF scales reduce respondent burden and are a useful tool to ascertain frequency of receipt of oral health behavior social support from family, health providers, and other/friend sources.

Valid, reliable measures of psychosocial constructs are needed in oral health research. This study quantitatively evaluated the psychometric properties of nine new Oral Health Behavior Social Support (OHBSS) scales, which measured support for three oral health behaviors (brushing, flossing, dental care), queried for each of three sources (family, health providers, others/friends). Young Mexican-origin adults in the southwestern United States-Mexico border region completed an online survey, in English or Spanish (N = 502). Survey items included: OHBSS scales, general social support scales, oral health behaviors, self-rated oral health status, dental anxiety, acculturation and socio-demographics. Subsample 1 participants also completed a dental exam (N = 41). Subsample 2 participants also completed a repeat OHBSS survey two-to-six weeks later (N = 56). Psychometric properties were tabulated, overall and by language preference (English or Spanish). Convergent and divergent validity were evaluated via correlations between the dental-specific OHBSS social support scales, scores from three validated general social support scales, and scales expected to be largely unrelated (acculturation, dental anxiety). Correlations examined predictive validity between the OHBSS scales and oral health behaviors, and self-reported and clinical outcomes. Test–retest reliability was assessed via intraclass correlation coefficients in Subsample 2. Of 502 participants, 60

This paper describes the simultaneous co-development of Oral Health Behavior Social Support (OHBSS) scales in English and Spanish. OHBSS scales assess social support for toothbrushing, flossing, and dental care utilization, which are targets for interpersonal-level interventions to promote oral health among Hispanic/Latino adults. The focus was on Mexican-origin adults, who comprise the largest United States Hispanic/Latino subgroup and experience a high oral disease burden. All participants self-identified as Mexican-origin adults (ages 21-40 years old), living along the California-Arizona-Mexico border. Independent samples were recruited for each study partnering with Federally Qualified Health Centers. First, we conducted semi-structured interviews about social support for oral health behaviors in August to November 2018 (Study 1, N = 72). Interviews were audio recorded, transcribed (in original language, Spanish or English), and qualitative data were coded and analyzed in Dedoose following three topical codebooks; excerpts were used to co-create the large bilingual item data bank (OHBSSv1). The item bank was pre-tested via 39 cognitive interviews between December 2019 to March 2020, reviewed by an expert panel with several bilingual members, reduced to 107 Spanish/109 English items (OHBSSv2), then pilot tested in January to December 2021 (Study 2, N = 309). Pilot survey data were analyzed through Exploratory Factor Analysis and Horn's parallel analysis, overall and by language, to examine response patterns and inform item selection (OHBSSv3). The scales queried social support for toothbrushing, flossing, and dental care utilization across 39 items from three sources (family, health providers, others/friends), plus up to nine optional dental care-related items (Study 3, conducted April 2022 to February 2023, N = 502). Confirmatory Factor Analysis (CFA) assessed model fit, overall and by language (multiple group CFA). Final OHBSS scales include 37 items, plus seven optional items. Acceptable model fit for three-factor structures for each oral health behavior was found, providing evidence of the scales' construct validity. Cronbach's alphas and McDonald's omegas were tabulated; all were above 0.95, overall and by language, supporting scales' internal consistency.

Gingipains, toxic protease virulence factors from the bacterial pathogen P. gingivalis ( Pg ), were discovered in postmortem brains of patients with Alzheimer’s disease. Gingipain levels correlated with tau and ubiquitin pathology, and oral infection of wild-type mice with Pg resulted in brain inflammation and neurodegeneration that was blocked by gingipain inhibitors. LHP588 is a second-generation orally bioavailable and brain-penetrant lysine gingipain inhibitor that reduces the toxicity of Pg and the bacterial load. A first-generation molecule (COR388/atuzaginstat) previously showed reduction of cognitive decline in prespecified cohorts defined by their infection load, but it was discontinued due to a hepatic safety signal. We will review new data from the LHP588 SAD/MAD, and the design of the Phase 2b study planned for initiation later this year. The Phase 1 study of LHP588 enrolled 32 individuals in the SAD component with 4 cohorts and concurrent placebo (25 mg, 50 mg, 100 mg, 200 mg) and 24 healthy subjects in the 10-day MAD portion, with 3 cohorts and concurrent placebo (50, 100 mg, and 200 mg). In the study of atuzaginstat, significance was not observed in the full intent-to-treat population, however, prespecified subgroup analyses indicated efficacy in patients with Pg -positive saliva ( Pg +), slowing cognitive decline compared with placebo on the ADAS-Cog11 by approximately 50% (p = 0.02). Changes in Pg DNA in saliva correlated significantly with changes on the ADAS-Cog, CDR-SB, and MMSE. The second-generation lysine gingipain inhibitor LHP588 was well-tolerated in the SAD and 10-day MAD study; adverse events in the active arms were mild and sporadic. PK with once-daily dosing achieved target concentrations sufficient for reduction of systemic Pg infection at doses >25 mg of LHP588, and exposures equivalent or greater than those achieved with the high dose of atuzaginstat. LHP588 was also detected in the CSF. LHP588 was well-tolerated in healthy volunteers without evidence of hepatic safety signals to date, and its PK profile was supportive of once daily dosing. The Phase 2 trial of LHP588 proposed to start in late 2023 will be similar in design to the prior atuzaginstat study but will be restricted to subjects with Pg + saliva.

Research in aging has significantly advanced; scientists are now able to identify interventions that slow the biologic aging processes (i.e., the “hallmarks of aging”), thus delaying the onset and progression of multiple diseases, including oral conditions. Presentations given during the 3-part session “Geroscience: Aging and Oral Health Research,” held during the 2023 American Association for Dental, Oral, and Craniofacial Research meeting, are summarized in this publication. Speakers’ topics spanned the translational research spectrum. Session 1 provided an overview of the geroscience and health span (disease-free and functional health throughout life) concepts. The common molecular mechanisms between oral cancer and aging were discussed, and research was presented that showed periodontal microflora as a potential factor in Alzheimer’s disease progression. Session 2 focused on behavioral and social science aspects of aging and their oral health significance. The keynote provided evidence that loneliness and isolation can have major health effects. These social conditions, along with poor oral health, tooth loss, and cognitive decline, could potentially affect healthy eating ability and systemic health in older adults. Research could help elucidate the directions and pathways connecting these seemingly disparate conditions. Session 3 focused on the delivery of oral care in different settings and the many barriers to access care faced by older adults. Research is needed to identify and implement effective technology and strategies to improve access to dental care, including new delivery and financing mechanisms, workforce models, interprofessional provider education and practice, and use of big data from medical–dental integration of electronic health records. Research to improve the “oral health span,” reduce oral health disparities, and increase health equity must be tackled at all levels from biologic pathways to social determinants of health and health policies.

Purpose of Review To establish a link or causation between periodontitis and Alzheimer’s disease requires studies that first establish an association or correlation between these two diseases, followed by in vitro, animal model, and human studies to identify possible underlying biological mechanisms, and finally assessing the benefits of periodontal therapy in general and targeted therapies against the microbiota and inflammatory responses in periodontitis. This review presents an update on the current correlation and biological mechanisms that link these two diseases, with special emphasis on the keystone periodontal pathogen Porphyromonas gingivalis and its key family of gingipain enzymes. Recent Findings Recent evidence for slowing the progression of Alzheimer’s disease through periodontal therapy in general, as well as focused therapies directed against Porphyromonas gingivalis and its gingipains, are presented. Summary These intervention studies, together with the recent association and biological mechanism studies, strengthen the evidence for a direct link or causation between these two diseases. In addition, these recent studies support the special role of the dental practitioner in the management of patients with cognitive decline.

Loss of cognitive function in the aging population, particular those with Alzheimer disease, presents unique challenges to health practitioners. For the dental practitioner these include management of periodontal diseases, caries, and other dental conditions in this special population. It is well established in the cognitively impaired patient that a lack of adherence to dental hygiene routines and professional care leads to increases in the prevalence and severity of these dental conditions, leading to increased loss of teeth. More recent evidence has indicated a possible role of the microbiota of dental plaque associated with periodontal diseases in the development and progression of Alzheimer disease, thereby supporting a two-way interaction of these two diseases. New therapies are needed to address the potential upstream events that may precede overt signs of Alzheimer disease. One of these approaches would be to target these various bacterial, viral, and other microbial pathogens associated with periodontal disease that can translocate into the bloodstream and then to distal sites, such as the brain. Such microbial translocation would lead to local inflammation and buildup of the hallmark signs of Alzheimer disease, including amyloid beta deposits, tau fragmentation and tangles, breakdown of host protective molecules, such as the apolipoproteins, and neuron toxicity. In this review, evidence for the biological basis of the role of the periodontal disease microflora on the initiation and progression of Alzheimer disease will be presented with a focus on the potential role of the keystone pathogen Porphyromonas gingivalis with its family of gingipain enzymes. The various mechanisms for which P. gingivalis gingipains may contribute to the initiation and progression of Alzheimer disease are presented. Small-molecule inhibitors of these gingipains and their effects on reducing biological markers of Alzheimer disease may have beneficial effects for the initiation and progression of loss of cognitive function in Alzheimer disease. In addition to these targeted therapies for specific periodontal pathogens, considerations for the dental practitioner in applying more general approaches to reducing the periodontal plaque microflora in the management of the cognitively impaired patient are discussed for this special population.

INTRODUCTION:The functional interplay between cementum of the root and alveolar bone of the socket is tuned by a uniquely positioned 70-80 µm wide fibrous and lubricious ligament in a dentoalveolar joint (DAJ). In this study, structural and biomechanical properties of the DAJ, periodontal ligament space (PDL-space also known as the joint space), alveolar bone of the socket, and cementum of the tooth root that govern the biomechanics of a lipopolysaccharide (LPS)-affected DAJ were mapped both in space and time. METHODS:The hemi-maxillae from 20 rats (4 control at 6 weeks of age, 4 control and 4 LPS-affected at 12 weeks of age, 4 control and 4 LPS-affected at 16 weeks of age) were investigated using a hybrid technique; micro-X-ray computed tomography (5 µm resolution) in combination with biomechanical testing in situ. Temporal variations in bone and cementum volume fractions were evaluated. Trends in mineral apposition rates (MAR) in additional six Sprague Dawley rats (3 controls, 3 LPS-affected) were revealed by transforming spatial fluorochrome signals to functional growth rates (linearity factor - RW) of bone, dentin, and cementum using a fast Fourier transform on fluorochrome signals from 100-µm hemi-maxillae sections. RESULTS:An overall change in LPS-affected DAJ biomechanics (a 2.5-4.5X increase in tooth displacement and 2X tooth rotation at 6 weeks, no increase in displacement and a 7X increase in rotation at 12 weeks; 27% increase in bone effective strain at 6 weeks and 11% at 12 weeks relative to control) was associated with structural changes in the coronal regions of the DAJ (15% increase in PDL-space from 0 to 6 weeks but only 5% from 6 to 12 weeks compared to control). A significant increase (p < 0.05) in PDL-space between ligated and age-matched control was observed. The bone fraction of ligated at 12 weeks was significantly lower than its age-matched control, and no significant differences (p > 0.05) between groups were observed at 6 weeks. Cementum in the apical regions grew faster but nonlinearly (11% and 20% increase in cementum fraction (CF) at 6 and 12 weeks) compared to control. Alveolar bone revealed site-specific nonlinear growth with an overall increase in MAR (108.5 µm/week to 126.7 µm/week after LPS treatment) compared to dentin (28.3 µm/week in control vs. 26.1 µm/week in LPS-affected) and cementum (126.5 µm/week in control vs. 119.9 µm/week in LPS-affected). A significant increase in CF (p < 0.05) in ligated specimens was observed at 6 weeks of age. CONCLUSIONS:Anatomy-specific responses of cementum and bone to the mechano-chemo stimuli, and their collective temporal contribution to observed changes in PDL-space were perpetuated by altered tooth movement. Data highlight the "resilience" of DAJ function through the predominance of nonlinear growth response of cementum, changes in PDL-space, and bone architecture. Despite the significant differences in bone and cementum architectures, data provided insights into the reactionary effects of cementum as a built-in compensatory mechanism to reestablish functional competence of the DAJ. The spatial shifts in architectures of alveolar bone and cementum, and consequently ligament space, highlight adaptations farther away from the site of insult, which also is another novel insight from this study. These adaptations when correlated within the context of joint function (biomechanics) illustrate that they are indeed necessary to sustain DAJ function albeit being pathological.

The United States continues to be an incubator for new concepts and approaches to the diagnosis, treatment, and prevention of periodontal diseases. This volume of Periodontology 2000 presents some of these newer areas of research and paradigms that have emerged in the United States from both long-established and new investigators. These areas include: (1) more comprehensive approaches to assessing the total periodontal microbiome, including bacteria, viruses, and fungi, and their interactions with both the local and systemic inflammatory and immune responses, as well as with other oral and systemic conditions and diseases; (2) new developments for a more comprehensive characterization of the patient genome, transcriptome, and proteome profiles and the role of these profiles in periodontal disease pathogenesis; (3) new developments in nonsurgical approaches to periodontal diseases, including broad-based lines of attack using natural antimicrobials and host-modulation therapies and more focused approaches that target specific interactions in the host response; and (4) new big data analysis, machine learning, and imaging approaches, both for understanding the pathogenesis of periodontal diseases and for developing improved risk-assessment tools and better treatment outcomes.

With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV-associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented. Also, the effects of HIV and combined antiretroviral therapies on comorbidities such as hyposalivation, dementia, and osteoporosis on periodontal disease progression are discussed.

Thursday, April 30April 14, 2020Free AccessCOR388 for the Treatment of Alzheimer’s Disease (4098)Michael Detke, Casey Lynch, Leslie Holsinger, Shirin Kapur, Dave Hennings, Debasish Raha, Sean Broce, … Show All … , Mai Nguyen, Florian Ermini, Ursula Haditsch, Mark Ryder, Ira Goodman, Stephen Thein, and Stephen Dominy Show FewerAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.4098 Letters to the Editor

Abstract COR388, a small‐molecule lysine‐gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine‐gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28‐day dose‐response study, COR388 inhibited the lysine‐gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine‐gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine‐gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine‐gingipain and eliminating P. gingivalis infection in humans.

Epidemiological studies have identified an association between periodontitis and Alzheimer disease (AD); however, the nature of this association has been unclear. Recent work suggests that brain colonization by the periodontal pathogenPorphyromonas gingivalismay link these two inflammatory and degenerative conditions. Evidence ofP. gingivalisinfiltration has been detected in autopsy specimens from the brains of people with AD and in cerebrospinal fluid of individuals diagnosed with AD. Gingipains, a class ofP. gingivalisproteases, are found in association with neurons, tau tangles, and beta-amyloid in specimens from the brains of individuals with AD. The brains of mice orally infected with P. gingivalis show evidence ofP. gingivalisinfiltration, along with various neuropathological hallmarks of AD. Oral administration of gingipain inhibitors to mice with established brain infections decreases the abundance ofP. gingivalisDNA in brain and mitigates the neurotoxic effects ofP. gingivalisinfection. Thus, gingipain inhibition could provide a potential approach to the treatment of both periodontitis and AD.

Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC–MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.

Spatial and temporal adaptations within periodontal tissues and their interfaces result from functional loads. Functional loads can be physiologic and/or pathologic in nature. The prolonged effect of these loads can alter the overall biomechanics of a dentoalveolar fibrous joint (dentoalveolar joint) by changing the form of the tooth root and its socket. This "sculpting" of the tooth root and alveolar bony socket is a consequence of several mechano-biological changes that occur within the periodontal complex of a load-bearing dentoalveolar joint. These include changes in biochemical expressions, structure, elemental composition, and mechanical properties of alveolar bone, the underlying tissues of the roots of teeth, and their interfaces. These physicochemical changes in tissues continue to prompt mechano-responsive biochemical activities at the attachment sites of periodontal ligament (soft) with bone (hard), and ligament with cementum (hard), which are the entheses of a load-bearing dentoalveolar joint. Forces at soft-hard tissue attachment sites between disparate materials with different stiffness values theoretically generate strain singularities or discontinuities. These discontinuities under prolonged functional loading increase the probability for failure to occur specifically at the enthesial zones. However, in a normal dentoalveolar joint, gradual stiffness gradients exist from ligament to bone, and from ligament to cementum. The gradual transitions in stiffness from softer ligament (lower stiffness) to harder bone or cementum (higher stiffness) or vice versa optimize tissue and interfacial strains. Optimization of tissue and ligament-enthesial physical and chemical properties facilitates transmission of cyclic forces of varying magnitudes and frequencies that collectively maintain the overall biomechanics of a dentoalveolar joint. The objectives of this review are 3-fold: (i) to illustrate physicochemical adaptations at the periodontal ligament entheses of a human periodontal complex affected by subgingival calculus; (ii) to demonstrate how to "program" the hallmarks of periodontitis in small-scale vertebrates in vivo to generate spatiotemporal maps of physicochemical adaptations in a diseased dentoalveolar joint; and (iii) to correlate dentoalveolar joint biomechanics in healthy and diseased states to spatiotemporal maps of physicochemical adaptations within respective periodontal tissues. This interdisciplinary approach demonstrates that physicochemical adaptations within periodontal tissues using the mechanics of materials (tissue mechanics), materials science (tissue composition), and mechano-biology (matrix molecules) can help explain the mechano-adaptation of dentoalveolar joints in normal and diseased functional states. Multiscale biomechanics and mechano-biology approaches can provide insights into the functional competence of a diseased relative to a normal dentoalveolar joint. Insights gathered from interdisciplinary and multiscale biomechanics approaches include the following: (i) physiologic loads related to chewing maintain a balance between mineral-forming and-resorbing biochemical cellular events, resulting in gradual stiffness gradients at the periodontal ligament entheses, and, in turn, sustain the overall biomechanics of a normal "healthy" dentoalveolar joint; (ii) pathologic loads resulting from tissue degradation and physical changes to the periodontal complex promote an abrupt stiffness gradient at the periodontal ligament entheses. The shift from gradual to an abrupt stiffness gradient could prompt a shift in the biochemical cascades, exacerbate mechano-responsive biochemical expressions at periodontal ligament entheses farther away from the site of insult, and culminate in joint degradation; (iii) sustained pathologic function on periodontally diseased joints exacerbates degradation of periodontal ligament entheses providing insights into "rescue therapy", such as the use of an adequate "mechanocal dose" to regain joint function; and (iv) spatiotemporal maps of changes in biochemical expressions, and physicochemical properties of strain-dominated affected sites, including the periodontal ligament entheses, can guide anatomy-specific therapeutics for tissue regeneration and/or disease control with the purpose of regaining dentoalveolar joint function. Modulation of occlusal loads could minimize disease progression and potentially assist in regaining functional attachment of ligament to bone and/or ligament to cementum of the dentoalveolar joint. Elucidating mechanisms that drive the breakdown of the functionally active periodontal complex burdened with microbes will provide the required critical insights into regenerative medicine and/or biomimetic approaches that would facilitate rescue/regain of dentoalveolar joint function.

RATIONALE & OBJECTIVE:Observational studies have suggested that periodontal disease may be a modifiable risk factor for chronic kidney disease (CKD). The Kidney and Periodontal Disease (KAPD) Study was designed to determine the feasibility of conducting a periodontal disease treatment trial among a high-risk (mostly poor and racial/ethnic minority) population and estimate the magnitude and variability of kidney and inflammatory biomarker levels in response to intensive periodontal treatment. STUDY DESIGN:Single-center, unmasked, intention-to-treat, randomized, controlled, pilot trial with 2:1 allocation to the treatment and comparison groups. SETTING & PARTICIPANTS:English- and Spanish-speaking individuals aged 20 to 75 years receiving primary care within the San Francisco Community Health Network with evidence of both moderate to severe periodontal disease and CKD. INTERVENTION:Immediate intensive nonsurgical periodontal treatment versus rescue treatment for progressive disease at baseline and 4, 8, and 12 months. OUTCOMES:Feasibility and process outcomes. Levels of biomarkers of kidney function, kidney injury, and systemic inflammation obtained at baseline and 4 and 12 months. RESULTS:KAPD randomly assigned 51 participants to the immediate (34 participants) or rescue (17 participants) groups. 14% dropped out of the study (4 immediate, 3 rescue) and 80% completed all 4 visits of the 12-month protocol (28 immediate, 13 rescue). Fewer than half the teeth recommended for extraction were extracted and 40% of immediate group visits were outside the protocol window. Bleeding on probing and probing depth improved more in the immediate group than in the rescue group; there was no significant separation in periodontal status. Levels of markers of vascular endothelial and systemic injury declined in both groups. LIMITATIONS:No true control group. CONCLUSIONS:This 12-month, pilot, randomized, controlled trial successfully recruited and retained a high-risk population but was less successful observing treatment adherence, treatment effect, and variability of biomarker levels. Although KAPD did not meet all of its goals, important lessons learned can be applied to future studies. FUNDING:National Institute of Diabetes and Digestive and Kidney Disease (Bethesda, MD; grant number 1K23DK093710-01A1) and Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation, Princeton, NJ. Funders had no role in study design; collection, analysis, or interpretation of data; writing the report; or the decision to submit the report for publication. TRIAL REGISTRATION:NCT01802216.

Gingipains from Porphyromonas gingivalis drive Alzheimer’s pathology and can be blocked with small-molecule inhibitors.