Microbial Interactions between Periodontal Disease and Dementia

Oral bacteria and bacterial byproducts have been found in brain tissue of patients with dementia at higher rates than in healthy controls.^4,5,8,71Additionally, serum antibodies to periodontopathogenic bacteria have been found to be in increased in patients with Alzheimer’s disease and dementia when compared to healthy individuals.^23,27,69 The question remains: how do these bacteria enter the brain? It has been proposed that such transport of bacteria into human neural tissues could occur through one of several mechanisms: 1) bacteremias are seen in patients with gingival inflammation and/or periodontitis, which may put the bacteria in proximity to the brain and in cases of a weakened blood-brain barrier (due to age, chronic infection, or inflammation) bacteria may cross the blood-brain barrier, 2) direct access to the brain could be accessed by bacteria entering perivascular spaces, and 3) oral bacteria may translocate to the brain directly through olfactory and/or trigeminal nerve pathways.⁸¹ Further, bacterial byproducts, including virulence factors such as lipopolysacchride, capsular material, proteolytic enzymes, and gingipains, may cross the blood-brain barrier through similar pathways and contribute to demential progression.^{1,2,20,62,82,83} A less-well investigated method for the interaction between periodontal disease and dementia may include alteration of gene expression caused by exposure to bacteria and their byproducts. In these cases, epigenetic alterations of intracellular DNA may change gene expression and up- or down-regulate the proteins that they code for. Bacteria and their byproducts increase DNA methylation and histone acetylation, which has been implicated in the development of many diseases.^84,85

Oral hygiene status in elderly dentate patients is inversely proportional to dementia severity and poor oral hygiene is associated with dementia development.⁸⁶ Reduction of the overall microbial burden, as well as a shift to a more eubiotic microbiome may be achieved through oral hygiene delivery.^87,88 This decreased microbial burden could lead to reduced bacteremias and therefore a reduction in the likelihood of bacteria and their byproducts crossing the blood-brain barrier.^4,5,89 Improved oral health, including advanced oral hygiene practices has been suggested as an intervention to reduce the direct and indirect influences of oral bacteria and their byproducts on the brain and their subsequent potential influence on cognitive decline.⁹⁰