Sore gums and Alzheimer’s — does dementia start in the mouth?

Aim of the study: Pre-clinical evidence implicates oral bacteria in the pathogenesis of Alzheimer's disease (AD), while clinical studies show diverse results. To comprehensively assess the association between oral bacteria and AD with clinical evidence.

Results: Of the 16 studies included, ten investigated periodontal pathobionts and six were microbiome-wide association studies. Samples from the brain, serum, and oral cavity were tested. We found over a ten-fold and six-fold increased risk of AD when there were oral bacteria (OR = 10.68 95% CI: 4.48-25.43; p < 0.00001, I2 = 0%) and Porphyromonas gingivalis (OR = 6.84 95% CI: 2.70-17.31; p < 0.0001, I2 = 0%) respectively in the brain. While AD patients exhibited lower alpha diversity of oral microbiota than healthy controls, the findings of bacterial communities were inconsistent among studies. The best evidence synthesis suggested a moderate level of evidence for an overall association between oral bacteria and AD and for oral bacteria being a risk factor for AD. Current evidence moderately supports the association between oral bacteria and AD, while the association was strong when oral bacteria were detectable in the brain.

Aim of the study: A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive disorders, dementia, and depression. This is especially true in cases of changes in diet, malnutrition, loss of muscular endurance, and abnormal systemic inflammatory response.

Results: Periodontal disease was found to be associated with both cognitive disorders (relative risk (RR) 1.25, 95% CI 1.11-1.40, in the analysis of cross-sectional studies); cognitive impairment (RR 3.01, 95% CI 1.52-5.95 for longitudinal studies, cognitive decline); and dementia (RR 1.22, 95% CI 1.10-1.36). However, no significant increased risk of depression among subjects with periodontal disease was found (RR 1.07, 95% CI 0.95-1.21). Despite the association with two of the three explored outcomes, the available evidence on periodontal diseases and dementia, cognitive disorders, and depression is controversial due to several limitations. Therefore, further investigations involving validated and standardized tools are required.

Aim of the study: The present umbrella review aims to assess the association between periodontitis and mild cognitive impairment(MCI), Alzheimer's disease and dementia.

Results: MEDLINE(via PubMed), Scopus, EMBASE, Google Scholar, and Cochrane Library was searched. Risk of Bias(ROB) was performed using Risk of Bias in Systematic Reviews (ROBIS) tool. Metaumbrella software was used for performing quantitative analysis, evidence stratification and GRADE analysis. 12 of the 14 included studies were judged to have a high ROB, while two systematic reviews and meta-analyses (SRMAs) demonstrated a low ROB. Individuals with periodontitis had a 1.651 times higher risk of developing MCI (95% CI = 1.391 to 1.96; I2 = 0%; P < 0.001), a 1.525 times higher risk of Alzheimer's disease (95% CI = 1.149 to 2.023; I2 = 85.877%; P < 0.001), and a 1.535 times higher risk of dementia (95% CI = 1.119 to 2.107; I2 = 82.972%; P < 0.001), all supported by Class IV evidence.

Aim of the study: The hypothesis of an infectious connection from the oro-pharyngeal sphere to the brain underlines the interest in analyzing the link between periodontal disease and Alzheimer's disease. The aim of this systematic review was to examine the link between Alzheimer's disease and periodontal disease in patients aged 65 and over.

Results: naeslundii (crude HR = 2.0 (1.1-3.8)). The presence of periodontitis at baseline was associated with a six-fold increase in the rate of cognitive decline over a 6-month follow-up period (ADAS-Cog mean change = 2.9 ± 6.6). The current review suggests an association between periodontal disease and Alzheimer's disease. The treatment of periodontal disease could be a way to explore Alzheimer's disease prevention.

Aim of the study: Periodontitis is a chronic non-communicable disease caused by a dysbiotic microbiota. Pathogens can spread to the bloodstream, colonize other tissues or organs, and favor the onset of other pathologies, such as Alzheimer's disease (AD).

Results: Infection with oral pathogens in animals was related to developing neuropathological characteristics of AD and bacteria detection in the brain. In patients with AD, oral bacteria were detected in brain tissues, and increased levels of pro-inflammatory cytokines were also detected. There is evidence of a microbiological susceptibility to develop AD when the most dysbiosis-associated oral bacteria are present. The presence of bacteria in the brain is related to AD's pathological characteristics, suggesting an etiological oral-brain axis.

Aim of the study: Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state.

Results: All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

Aim of the study: We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health.

Results: In fully adjusted models, having more teeth was associated with lower odds for infarcts, lower white matter hyperintensity (WMH) volume, higher entorhinal cortex volume, and higher cortical thickness. Higher extent of periodontitis was associated with lower entorhinal cortex volume and lower cortical thickness. Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses and MRI outcomes.

Aim of the study: Periodontitis is a risk factor linked to Alzheimer's disease (AD), and characterized by amyloid-beta (Aβ) pathology. Mounting evidence suggests a contributory role of periodontitis in the onset and progression of AD. Type I interferons are upregulated in Porphyromonas gingivalis (Pg)-induced periodontitis in murine models. Colonization of Pg has been identified in the brains of patients with AD.

Results: Pg-induced periodontitis led to cognitive impairment in C57BL/6J mice and exacerbated a cognitive decline in APP/PS1 mice. Furthermore, Pg-induced periodontitis elevated the levels of interferon (IFN)-β, IFITM3, and Aβ deposition in the brains of both C57BL/6J and APP/PS1 mice. We also identified Pg DNA, glial activation, and the expression of inflammatory mediators in the brain of a Pg-induced periodontitis model. Additionally, our findings confirmed astrocytes as the primary responders to Pg-induced innate immunity and inflammation both in vitro and in vivo. Periodontitis also induces an increase in IFITM3 expression in periodontal tissue, salivary glands.

Aim of the study: Porphyromonas gingivalis (PG)-infected periodontitis is in close connection with the development of Alzheimer's disease (AD). PG-derived extracellular vesicles (pEVs) contain inflammation-inducing virulence factors, including gingipains (GPs) and lipopolysaccharide (LPS). To understand how PG could cause cognitive decline, we investigated the effects of PG and pEVs on the etiology of periodontitis and cognitive impairment in mice.

Results: pEVs contained neurotoxic GPs and inflammation-inducible fimbria protein and LPS. Gingivally exposed, but not orally gavaged, PG or pEVs caused periodontitis and induced memory impairment-like behaviors. Gingival exposure to PG or pEVs increased TNF-α expression in the periodontal and hippocampus tissues. They also increased hippocampal GP+Iba1+, LPS+Iba1+, and NF-κB+Iba1+ cell numbers. Gingivally exposed PG or pEVs decreased BDNF, claudin-5, and N-methyl-D-aspartate receptor expression and BDNF+NeuN+ cell number. Gingivally exposed fluorescein-5-isothiocyanate-labeled pEVs (F-pEVs) were detected in the trigeminal ganglia and hippocampus. However, right trigeminal neurectomy inhibited the translocation of gingivally injected F-EVs into the right trigeminal ganglia. Gingivally exposed PG or pEVs increased blood LPS and TNF-α levels. Furthermore, they caused colitis and gut dysbiosis. Gingivally infected PG, particularly pEVs, may cause cognitive decline with periodontitis.