Oral Inflammation, Tooth Loss, Risk Factors, and Association with Progression of Alzheimer's Disease

Abstract

Periodontitis is a polymicrobial chronic inflammatory disease of tooth-supporting tissues with bacterial etiology affecting all age groups, becoming chronic in a subgroup of older individuals. Periodontal pathogens Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are implicated in the development of a number of inflammatory pathologies at remote organ sites, including Alzheimer's disease (AD). The initial inflammatory hypothesis proposed that AD hallmark proteins were the main contributors of central nervous system (CNS) inflammation. This hypothesis is expanding to include the role of infections, lifestyle, and genetic and environmental factors in the pathogenesis of AD. Periodontal disease (PD) typifies a condition that encompasses all of the above factors including pathogenic bacteria. These bacteria not only are the source of low-grade, chronic infection and inflammation that follow daily episodes of bacteremia arising from everyday tasks such as brushing, flossing teeth, chewing food, and during dental procedures, but they also disseminate into the brain from closely related anatomical pathways. The long-term effect of inflammatory mediators, pathogens, and/or their virulence factors, reaching the brain systemically or otherwise would, over time, prime the brain's own microglia in individuals who have inherent susceptibility traits. Such susceptibilities contribute to inadequate neutralization of invading agents, upon reaching the brain. This has the capacity to create a vicious cycle of sustained local inflammatory milieu resulting in the loss of cytoarchitectural integrity and vital neurons with subsequent loss of function (deterioration in memory). The possible pathways between PD and AD development are considered here, as well as environmental factors that may modulate/exacerbate AD symptoms.

Inflammasome Involvement in Alzheimer’s Disease

“…The olfactory and trigeminal nerves are known to be used by periodontal pathogens to bypass the BBB for direct passage to the CNS (5,150,159,160). Identification of oral treponemes in the trigeminal ganglia supports such a route of dissemination (5).…”

“…Thus, polymorphisms that increase TNF-α also increase the risk of both AD and periodontitis (172, factors (12,13). Elderly often show neglect of oral hygiene which can stimulate recurrent chronic oral infection (150). This again promotes inflammation which can lead to confusion and dementia (3,4,154).…”

“…Blood stream dissemination 19 The most likely pathway for dissemination of oral microorganisms to the brain is through the blood stream (150). Dental treatment as well as brushing, flossing, chewing and use of tooth picks in a patient with periodontitis will release a bacteraemia (151).…”

“…The olfactory and trigeminal nerves are known to be used by periodontal pathogens to bypass the BBB for direct passage to the CNS (5,150,159,160). and dementia (3,4,154).…”

Link between Periodontal Disease and Coronary Artery Disease: Bangladesh Perspective

“…53 Among the rural school children between 5 to 15 years, the prevalence of dental caries, plaque, gingival bleeding and bleeding on probing was 69.6%, 91.6%, 66.8 % and 64% respectively. 54 The Link between PD and CAD Periodontitis has been found to be associated with a number of systemic diseases and conditions, including stroke, 55 peripheral arterial disease, 56 type 2 diabetes, 57 rheumatoid arthritis, 58 chronic kidney disease, 59 and chronic obstructive pulmonary disease, 60 Alzheimer's disease, 61 cancers, 62 anaemia, 63 and low-birth weight baby. [64][65] Currently, however, there is a lack of consensus among experts on the nature of these associations and confusion among health care providers and the public on how to interpret this rapidly growing body of science.…”