Long-term sorbitol consumption affects the hippocampus and alters cognitive function in aged mice.

The systemic effects of the artificial sweetener sorbitol on older adult individuals have not been elucidated. We assessed the effects of sorbitol consumption on cognitive and gingival health in a mouse model. Aged mice were fed 5% sorbitol for 3 months before their behavior was assessed, and brain and gingival tissues were collected. Long-term sorbitol consumption inhibited gingival tissue aging in aged mice. However, it caused cognitive decline and decreased brain-derived neurotrophic factor (BDNF) in the hippocampus. Sorbitol consumption did not affect homeostatic function; however, it may exert effects within the brain, particularly in the hippocampus.

Novel Catalytic Antioxidant Formulation Decreases Oxidative Stress, Neuroinflammation and Cognitive Dysfunction in a Model of Nerve Agent Intoxication.

Reactive oxygen species have an emerging role in the pathologic consequences of status epilepticus. We have previously demonstrated the efficacy of a water-for-injection formulation of the meso-porphyrin catalytic antioxidant, manganese (III) meso-tetrakis (N-N-diethylimidazole) porphyrin (AEOL10150) against oxidative stress, neuroinflammation, and neuronal death initiated by kainic acid, pilocarpine, diisopropylflurophosphate (DFP), and soman. This previous dose and dosing strategy of AEOL10150 required smaller multiple daily injections, precluding our ability to test its efficacy against delayed consequences of nerve agent exposure such as neurodegeneration and cognitive dysfunction. Therefore, we developed formulations of AEOL10150 designed to deliver a larger dose once daily with improved brain pharmacodynamics. We examined four new formulations of AEOL10150 that resulted in 8 times higher subcutaneous dose with lower acute toxicity, slower absorption, longer half-life, and higher maximal plasma concentrations compared with our previous strategy. AEOL10150 brain levels exhibited improved pharmacodynamics over 24 hours with all four formulations. We tested a subcutaneous dose of 40 mg/kg AEOL10150 in two formulations (2% carboxymethyl cellulose and 4% polyethylene glycol-4000) in the DFP rat model, and both formulations exhibited significant protection against DFP-induced oxidative stress. Additionally, and in one formulation (4% polyethylene glycol-4000), AEOL10150 significantly protected against DFP-induced neuronal death, microglial activation, delayed memory impairment, and mortality. These results suggest that reformulation of AEOL10150 can attenuate acute and delayed outcomes of organophosphate neurotoxicity. SIGNIFICANCE STATEMENT: Reformulation of manganese (III) meso-tetrakis (N-N-diethylimidazole) porphyrin allowed higher tolerated doses of the compound with improved pharmacodynamics. Specifically, one new formulation allowed fewer daily doses and improvement in acute and delayed outcomes of organophosphate toxicity.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

Association between Periodontitis and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

INTRODUCTION: The connection between periodontitis and mild cognitive impairment (MCI) continues to receive attention. However, whether periodontitis is a risk factor for MCI remains still uncertain. This study aims to systematically analyze the available literature regarding the relationship between periodontitis and the risk of developing MCI and whether the periodontal health of MCI patients is poorer. METHODS: A literature search of PubMed, Scopus, Embase, and Web of Science databases was conducted to include all studies on the relationship between periodontitis and MCI from inception to April 2023. The studies were independently screened by 2 researchers, and those meeting the inclusion criteria were extracted and cross-checked. Pooled odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) was calculated using either a fixed-effects or random-effects model. RESULTS: Seven studies with a total of 3,973 participants were included. Meta-analysis results showed a statistically significant higher incidence of MCI in patients with periodontitis (OR, 1.70 (95% CI: 1.24-2.32, p < 0.001) compared to healthy participants. A subgroup meta-analysis showed that the pooled OR for the risk of MCI in patients with severe periodontitis was 2.09 (95% CI: 1.49-2.92, p < 0.001). In addition, attachment loss (MD = 0.44, 95% CI: 0.12-0.75, p < 0.001) and plaque index (MD = 0.72, 95% CI: 0.50-0.93, p < 0.001) were higher in MCI patients compared with the control group, but the pocket probing depth (MD = 0.21, 95% CI: -0.08 to 0.49, p = 0.15) was not significantly different between the two groups. CONCLUSIONS: Patients with periodontitis are at a higher risk of developing MCI, and the periodontal health of MCI patients is generally compromised. However, further well-designed studies should be conducted to confirm this relationship between MCI and periodontitis.

Asian Cohort for Alzheimer Disease (ACAD) Pilot Study: Vietnamese Americans.

INTRODUCTION: The objective of this pilot study was to establish the feasibility of recruiting older Vietnamese Americans for research addressing genetic and nongenetic risk factors for Alzheimer disease (AD). METHODS: Twenty-six Vietnamese Americans were recruited from communities in San Diego. A Community Advisory Board provided cultural and linguistic advice. Bilingual/bicultural staff measured neuropsychological, neuropsychiatric, lifestyle, and medical/neurological functioning remotely. Saliva samples allowed DNA extraction. A consensus team reviewed clinical data to determine a diagnosis of normal control (NC), mild cognitive impairment (MCI), or dementia. Exploratory analyses addressed AD risk by measuring subjective cognitive complaints (SCC), depression, and vascular risk factors (VRFs). RESULTS: Twenty-five participants completed the study (mean age=73.8 y). Eighty percent chose to communicate in Vietnamese. Referrals came primarily from word of mouth within Vietnamese communities. Diagnoses included 18 NC, 3 MCI, and 4 dementia. Participants reporting SCC acknowledged more depressive symptoms and had greater objective cognitive difficulty than those without SCC. Eighty-eight percent of participants reported at least 1 VRF. DISCUSSION: This pilot study supports the feasibility of conducting community-based research in older Vietnamese Americans. Challenges included developing linguistically and culturally appropriate cognitive and neuropsychiatric assessment tools. Exploratory analyses addressing nongenetic AD risk factors suggest topics for future study.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Association Between Tongue Pressure and Prevalence of Mild Cognitive Impairment in Japan.

OBJECTIVE: Although it has been suggested that a decline in oral function is one of the potential risk factors affecting mild cognitive impairment (MCI), evidence is insufficient to draw clear conclusions. This Japanese cross-sectional study examined the association between tongue pressure (TP) and MCI in middle-aged and older adults aged 36-84 years. METHODS: Study participants were 1019 (368 men and 651 women). TP was evaluated using a TP measurement device. The maximum value of three measurements was used for analysis. MCI was defined as being present if a participant had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, smoking status, alcohol consumption, leisure-time physical activity, body mass index, hypertension, dyslipidemia, diabetes mellitus, history of depression, number of teeth, employment, education, and household income. RESULTS: The prevalence of MCI was 45.3%. Among women, compared with the lowest tertile of TP, the second and highest tertiles were significantly associated with a lower prevalence of MCI with a clear dose-response relationship; the adjusted odds ratio (95% confidence intervals) in the second and highest tertiles of TP were 0.54 (0.36-0.83) and 0.55 (0.36-0.84), respectively (p for trend = 0.005). In contrast, no statistically significant association was observed between TP and the prevalence of MCI among men. CONCLUSIONS: Our findings suggest that higher TP might be inversely associated with the prevalence of MCI in middle-aged and older Japanese women.

Distinctive subgingival microbial signatures in older adults with different levels of cognitive function.

AIM: To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. MATERIALS AND METHODS: We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). RESULTS: The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873-0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini-Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. CONCLUSIONS: This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment.

Gingipains may be one of the key virulence factors of Porphyromonas gingivalis to impair cognition and enhance blood-brain barrier permeability: An animal study.

AIM: Blood-brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. MATERIALS AND METHODS: C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav-1 levels were measured. The mechanisms of Ddx3x-induced regulation on Mfsd2a by arginine-specific gingipain A (RgpA) in BMECs were explored. RESULTS: P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up-regulated Cav-1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav-1 regulatory axis was activated. CONCLUSIONS: Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav-1 axis.

Population-level trends in self-reported healthcare utilization among older adults in Mexico with and without cognitive impairment.

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico. METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and being screened for cholesterol, diabetes, and hypertension in the past two years. Cognitive impairment was defined using a modified version of the Cross Cultural Cognitive Examination that assessed verbal memory, visuospatial and visual scanning. Total sample included 5,673 participants with cognitive impairment and 34,497 without cognitive impairment interviewed between 2001 and 2018. Generalized Estimating Equation models that adjusted for time-varying demographic and health characteristics and included an interaction term between time and cognitive status were used. RESULTS: For all participants, the risk for one or more overnight hospital stays, doctor visits, and dental visits in the past year, and being screened for diabetes, hypertension, and high cholesterol increased from 2001 to 2012 and leveled off or decreased in 2015 and 2018. Conversely, seeing a homeopathic doctor decreased. Cognitive impairment was associated with higher risk of hospitalization (RR = 1.13, 1.03-1.23) but lower risk of outpatient services (RR = 0.95, 0.93-0.97), cholesterol screening (RR = 0.93, 0.91-0.96), and diabetes screening (RR = 0.95, 0.92-0.97). No significant difference was observed in the use of pharmacists, homeopathic doctors, or folk healers based on cognitive status. Interaction effects indicated participants with cognitive impairment had lower risk for dental visits and hypertension screening but that these trajectories differed over time compared to participants without cognitive impairment. CONCLUSIONS: We identified distinct population-level trends in self-reported healthcare utilization and differences according to cognitive status, particularly for elective and screening services. These findings highlight the necessity for policy interventions to ensure older adults with cognitive impairment have their healthcare needs met.

Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults especially for females: a cross-sectional study.

BACKGROUND: Oral frailty is reported to increase the risk of new onset of mild cognitive impairment. Whereas, the association of oral frailty with cognition among older adults in both physical frail and non-physical frail status has not been sufficiently explored, and whether there are sex differences in the association is unclear. This study investigated the association of oral frailty and physical frailty with global cognitive function and executive function among older adults, as well as the sex differences in such association. METHODS: This cross-sectional study included 307 participants aged ≥ 60 years old from communities between June 2023 and August 2023, in Nanjing, China. Global cognitive function and executive function were assessed by using the Montreal Cognitive Assessment (MoCA) and Trail Making Tests A (TMT-A), respectively. Oral frailty was identified by the combination of natural tooth, Oral Frailty Index-8 (OFI-8), and oral diadochokinesis. Physical frailty was measured by using Fried phenotype model which contained 5 criteria: unintentional weight loss, weakness, exhaustion, slowness, and low physical activity. Multiple linear regression analyses for overall participants and stratified by sex and presence or absence of physical frailty were performed, respectively, to examine the association between oral frailty and cognitive functions. RESULTS: The median age of participants was 70 years old. The study included 158 (51.5%) females, 53 (17.3%) individuals with physical frailty, and 65 (21.2%) participants with oral frailty. After adjustment, the association between oral frailty and global cognitive function was observed in the physical frailty group (B = -2.67, 95% Confidence Interval [CI]: -5.27 to -0.07, p = 0.045) and the females with physical frailty (B = -4, 95% CI: -7.41 to -0.58, p = 0.024). Oral frailty was associated with executive function in overall participants (B = 0.12, 95% CI: 0.01 to 0.22, p = 0.037), physical frailty group (B = 23.68, 95% CI: 1.37 to 45.99, p = 0.038). In the adjusted models, oral frailty was significantly associated with executive function in all females (B = 0.21, 95% CI: 0.05 to 0.36, p = 0.009), in females without physical frailty (B = 0.19, 95% CI: 0.02 to 0.36, p = 0.027), and in females with physical frailty (B = 48.69, 95% CI: 7.17 to 90.21, p = 0.024). CONCLUSIONS: Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults, particularly among females. It is ponderable to consider sex differences and facilitate the management of physical frailty when it comes to promoting cognitive health based on the perspective of oral health among older adults.

A prospective association between social isolation and cognitive performance among older adults in Europe: the role of loneliness and poor oral health.

OBJECTIVES: The relationship between social isolation, loneliness, and tooth loss and cognition in older people is poorly understood. We examine how social isolation and cognitive performance are associated prospectively among older adults, as well as how tooth loss and loneliness are related to this association. METHODS: Using data from 26,168 participants aged ≥50 from the Survey of Health, Ageing and Retirement in Europe (SHARE), we explored the association between social isolation, loneliness, tooth loss and cognition. We used bootstrapping with resampling strategies for testing a moderated mediating model. RESULTS: Higher social isolation was associated with poorer cognitive performance (B = -0.20, 95% CI = -0.03, -0.01; R2 =0.60), an association mediated by the respondent's number of missing teeth (B = -0.001, 95% CI = -0.002, -0.001). Higher levels of social isolation were associated with a greater number of missing teeth, and a higher number of missing teeth was linked with poorer cognition. We also found that loneliness moderated the relationship between social isolation and both the number of missing teeth (B = -0.11, p = 0.047) and cognitive performance. CONCLUSION: In later life, social isolation and loneliness are associated with shoddy oral health and poor cognitive status. Clinicians and policymakers should be aware of both the association between social isolation and feelings of loneliness on dentition and oral health and their relationship to the cognitive status of older adults.

Association between tooth loss-related speech and psychosocial impairment with cognitive function: A pilot study in Hong Kong's older population.

BACKGROUND: Tooth loss has been associated with cognitive decline, but the underlying mechanisms involving speech and psychosocial impairment remain unclear. OBJECTIVES: To investigate the impact of tooth loss-related speech and psychosocial impairment on cognitive function in Hong Kong's older population. METHODS: Seventy-six Cantonese-speaking participants between the ages of 51-92 were classified into three groups: patients with complete dentures (CD), partially edentulous patients with less than 10 occluding tooth pairs (OU <10), and at least 10 occluding tooth pairs (OU ≥10). Cognitive function was assessed using the Montreal Cognitive Assessment Hong Kong Version, One-minute Verbal Fluency Task and Hayling Sentence Completion Test. Objective and subjective speech assessments were carried out using artificial intelligence speech recognition algorithm and a self-designed speech questionnaire. The impact of tooth loss on psychosocial condition was evaluated by the Reading the Mind in the Eyes Test and a self-designed questionnaire. Statistical analyses (one-way ANOVA, ANCOVA, Kruskal-Wallis test, Spearman correlation test) were performed. RESULTS: Tooth loss was significantly associated with lower cognitive function (p = .008), speech accuracy (p = .018) and verbal fluency (p = .001). Correlations were found between cognitive function and speech accuracy (p < .0001). No significant difference in tooth loss-related psychosocial impact was found between the three groups. CONCLUSION: While warranting larger sample sizes, this pilot study highlights the need for further research on the role of speech in the association between tooth loss and cognitive function. The potential cognitive impact of tooth retention, together with its known biological and proprioceptive benefits, supports the preservation of the natural dentition.

Are demographic factors, masticatory performance and structural brain signatures associated with cognitive impairment in older people? A pilot study of cross-sectional neuroimaging data.

BACKGROUND: The occurrence of cognitive impairment (CI) is expected to increase within an ageing population. CI is associated with tooth loss, which influences masticatory performance. A decrease in masticatory performance may cause functional and morphological changes in the brain. However, whether CI is associated with masticatory performance, demographics, and structural brain signatures has not been studied yet. OBJECTIVES: To assess the associations between CI on the one hand, and masticatory performance, demographic factors, and structural brain signatures (i.e. cortical volume and thickness) on the other hand. METHODS: In total, 18 older adults with CI (mean ± SD age = 72.2 ± 9.5 years) and 68 older adults without CI (65.7 ± 7.5 years) were included in this study. Masticatory performance was quantified using a colour-changeable chewing gum. A Magnetic Resonance Imaging (MRI) scan was used to map structural brain signatures. To study our aim, a multivariate binary logistic regression analysis with backward selection was performed. RESULTS: The cortical volume of the right entorhinal cortex was negatively associated with CI (p < .01). However, demographic factors, masticatory performance, and the other structural brain signatures under investigation were not associated with CI. CONCLUSION: A decrease in the volume of the right entorhinal cortex is associated with CI in older people.

Functional teeth and cognitive function among the Chinese elderly: The chain mediating effect of depressive symptoms and social participation.

The objective of this study was to investigate the chain mediating effects of depressive symptoms and social participation between functional teeth and cognitive function based on the biopsychosocial model. Data from the 2018 China Health and Retirement Longitudinal Study were analyzed. The findings revealed a favorable connection between the lack of edentulism and cognitive function, persisting even when accounting for the mediating factors of denture usage, depressive symptoms, and social participation. Furthermore, the study identified six indirect pathways in this relationship. The present study has substantiated the correlation between edentulism and cognitive function, thereby proposing that interventions aimed at denture usage, depressive symptoms, and social participation could potentially serve as preventive measures against cognitive decline in elderly individuals afflicted with edentulism. This underscores the significance of addressing these factors to alleviate cognitive decline.

No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research. METHODS: We incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance. RESULTS: In the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis. CONCLUSIONS: The MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.

Does periodontitis have any association with mild cognitive impairment?

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 I2 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.

Short-term data suggests cognitive benefits in the elderly with single-implant overdentures.

DESIGN: This study was an extension of a randomized crossover clinical trial approved by the institutional ethics committee (approval number: D2014-148) and adhered to the CONSORT guidelines. The original study juxtaposed patient contentment with single-implant overdentures (1-IODs) against conventional complete dentures (CCDs), with patient satisfaction being the primary focus. In this follow-up study, the cognitive function of edentulous patients receiving 1-IODs was assessed, specifically monitoring for the emergence of mild cognitive impairment (MCI) throughout a three-year period. Patient outcomes were systematically recorded at predetermined intervals: initially, two months post-1-IOD placement, after one year (with groups alternated between denture types at eight-month marks), then after two and three years. A prosthodontist with a decade of expertise performed all denture-related procedures. This follow-up emphasized the cognitive outcomes using the Montreal Cognitive Assessment (MoCA-J), considering it alongside previously documented results on masticatory function, bone resorption, survival rates, and patient-reported outcomes. CASE SELECTION: Between 2015 and 2016, a follow-up study enrolled edentulous patients over 50 years of age who were proficient in Japanese, had sufficient mandibular bone for implants, and were free of systemic health issues and habits that could impact oral health. The participants were randomly divided into two groups after receiving a central mandibular implant. Group 1 initially used 1-IODs, and Group 2 used unloaded CCDs. After two months and subsequent periods, they swapped denture types. Eventually, all patients chose 1-IODs for continued use. Implant success was monitored over three years. The design featured block randomization and accounted for a sample size of 22, determined to be sufficient for evaluating the primary outcome of patient satisfaction. All patients underwent careful allocation and received customized dental interventions, with detailed radiographic planning and surgical precision guiding the implantation process. DATA ANALYSIS: Multivariable linear mixed models were used to assess within-group changes in both overall and specific cognitive function scores across five timepoints. Age, assessment interval, and upper jaw denture status were incorporated as consistent variables, while individual participants were considered variable elements in the analysis. SPSS software version 22.0 was utilized to conduct the statistical tests, and a p value threshold of 0.05 was predetermined to establish statistical significance. RESULTS: Twenty-two patients with edentulous mandibles received 1-IODs. Memory and executive functions saw significant score increases at multiple timepoints over the three-year period, with statistical significance. Though one participant dropped out and another passed away, and two did not complete the 3-year follow-up, the remaining 18 participants provided comprehensive data. Age and type of maxillary denture were significant factors, influencing MoCA-J scores with older participants and those with fixed dentures showing lower scores in certain domains. Overall, the findings illustrated the positive correlation between 1-IODs and cognitive function in older adults. CONCLUSIONS: Older adults with no natural teeth left in their mandible showed improved cognitive function after one and three years of using 1-IODs, as reflected by their total and specific cognitive domain scores. The study suggests that such implant therapy may offer protective benefits against cognitive decline, demonstrating clinical relevance for patient care, regardless of the maxillary arch (antagonist) condition.

Exogenous monocyte myeloid-derived suppressor cells ameliorate immune imbalance, neuroinflammation and cognitive impairment in 5xFAD mice infected with Porphyromonas gingivalis.

BACKGROUND: Periodontitis is closely associated with the pathogenesis of Alzheimer's disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, has been reported in our recent study to cause immune-overreaction and induce cognitive impairment. Monocytic myeloid-derived suppressor cells (mMDSCs) possess potent immunosuppressive function. It is unclear whether mMDSCs-mediated immune homeostasis is impaired in AD patients with periodontitis, and whether exogenous mMDSCs could ameliorate immune-overreaction and cognitive impairment induced by Pg. METHODS: To explore the influence of Pg on cognitive function, neuropathology and immune balance in vivo, 5xFAD mice were treated with live Pg by oral gavage, three times a week for 1 month. The cells of peripheral blood, spleen and bone marrow from 5xFAD mice were treated with Pg to detect the proportional and functional alterations of mMDSCs in vitro. Next, exogenous mMDSCs were sorted from wild-type healthy mice and intravenously injected into 5xFAD mice that were infected with Pg. We used behavioral tests, flow cytometry and immunofluorescent staining to evaluate whether exogenous mMDSCs could ameliorate the cognitive function, immune homeostasis and reduce neuropathology exacerbated by Pg infection. RESULTS: Pg exacerbated cognitive impairment in 5xFAD mice, with the deposition of amyloid plaque and increased number of microglia in the hippocampus and cortex region. The proportion of mMDSCs decreased in Pg-treated mice. In addition, Pg reduced the proportion and the immunosuppressive function of mMDSCs in vitro. Supplement of exogenous mMDSCs improved the cognitive function, and enhanced the proportions of mMDSCs and IL-10+ T cells of 5xFAD mice infected with Pg. At the same time, supplement of exogenous mMDSCs increased the immunosuppressive function of endogenous mMDSCs while decreased the proportions of IL-6+ T cells and IFN-γ+ CD4+ T cells. In addition, the deposition of amyloid plaque decreased while the number of neurons increased in the hippocampus and cortex region after the supplement of exogenous mMDSCs. Furthermore, the number of microglia increased with an increase in the proportion of M2 phenotype. CONCLUSIONS: Pg can reduce the proportion of mMDSCs, induce immune-overreaction, and exacerbate the neuroinflammation and cognitive impairment in 5xFAD mice. Supplement of exogenous mMDSCs can reduce the neuroinflammation, immune imbalance and cognitive impairment in 5xFAD mice infected with Pg. These findings indicate the mechanism of AD pathogenesis and Pg-mediated promotion of AD, and provide a potential therapeutic strategy for AD patients.

The impact of study factors in the association of periodontal disease and cognitive disorders: systematic review and meta-analysis.

AIM: The aim was to assess study factors that impact the association of cognitive disorders in people with periodontal disease (PD). METHOD: Medline, EMBASE and Cochrane databases were searched until February 2022 using keywords and MeSH: (periodon* OR tooth loss OR missing teeth) AND (dementia OR Alzheimer's Disease OR cognitive*). Observational studies reporting prevalence or risk of cognitive decline, dementia or Alzheimer's disease (AD) in people with PD compared with healthy controls were included. Meta-analysis quantified the prevalence and risk (relative risk[RR]) of cognitive decline, dementia/AD, respectively. Meta-regression/subgroup analysis explored the impact of study factors including PD severity and classification type, and gender. RESULTS: Overall, 39 studies were eligible for meta-analysis: 13 cross-sectional and 26 longitudinal studies. PD demonstrated increased risks of cognitive disorders (cognitive decline-RR = 1.33, 95% CI = 1.13-1.55; dementia/AD-RR = 1.22, 95% CI = 1.14-1.31). Risk of cognitive decline increased with PD severity (moderate-[RR] = 1.14, 95% confidence interval [CI] = 1.07-1.22; severe-RR = 1.25, 95% CI = 1.18-1.32). For every 10% population increase in females, the risk of cognitive decline increased by 34% (RR = 1.34, 95% CI = 1.16-1.55). Self-reported PD showed a lower risk of cognitive disorders compared with clinical classification (cognitive decline-RR = 0.77, 95% CI = 0.65-0.91; dementia/AD-RR = 0.86, 95% CI = 0.77-0.96). CONCLUSION: The prevalence and risk estimates of cognitive disorders in association with PD can be influenced by gender, the disease classification of PD and its severity. Further homologous evidence taking these study factors into consideration is needed to form robust conclusions.