Synopsis
Links between periodontitis and neurodegenerative conditions have been determined with periodontal pathogens identified in amyloid plaques. The evidence is still emerging but sufficient to indicate that monitoring and management of oral health diseases is a modifiable risk factor in patients with neurodegenerative diseases.
- 1. Translocation of oral pathogen
- 2. Systemic inflammation
- 3. Platelet aggregation protein
Information
Average life expectancies are increasing globally. Dental management of the aging population can come with some challenges including reduced dexterity of the patient, immunosenescence and reduced cognitive functioni.
It should be noted that these three factors do increase the risk of developing dental diseases and influence not only the incidence but severity.
The Australian Bureau of Statistics (2018) noted that 38% of older Australians required assistance with everyday activities. 18.1% of these people were identified to require assistance with cognitive tasksii. There is emerging evidence indicating that periodontal pathogens, host responses and genetics are linked to the initiation and progression of neurodegenerative diseasesi. This article will focus on these possible connections.
Numerous studies have demonstrated that the risk of developing cognitive decline increased in elderly patients with gingival diseaseiii,iv. Some of these studies have also assessed biological markers of periodontal disease and periodontal microorganisms with relation to Alzheimer’s diseasev. Many periodontal pathogens have been implicated in the progression of cognitive decline, however, the keystone pathogen Porphymonas gingivalis (P. gingivalis) has been the most extensively studied. Patients with higher antibody tiers to P. gingivalis were more likely to have Alzheimer disease and scored poorer in cognitive decline tests. Higher antibody tiers were also associated with higher levels of amyloid beta in cerebrospinal fluid. Kamer et al. found that the level of amyloid beta deposits increased with severity of periodontal diseasevi. This literature supports a positive association between periodontal disease and decline in cognitive function.
Studies have shown that both bacteria and viruses from the oral cavity are implicated in neuroinflammatory responses. P. gingivalis is thought to play a central role in Alzheimer disease due to studies in postmortem patients and animal studies showing preferential invasion of this pathogen into regions of the brain responsible for memoryi. P. gingivalis is capable of invading endothelial cells, secreting gingipan prosteases that can break down the tight junctions of the blood-brain barrier and suppress the local host defence responsevii. The suppression of the immune system is also thought to contribute to an inhibition in removal of amyloid plaque. The translocation of P. gingivalis to the brain may also trigger inflammatory responses that can damage and occlude the microvasculature of the brain contributing to microstrokes and cognitive declinei. Viruses from the herpes family may also translocate to the brain or travel to regions of the brain after remaining dormant in the trigeminal nerve. Like P. gingivalis, herpetic viral loads have been correlated to the development of amyloid plaques. Periodontitis is also thought to contribute to low-grade systemic inflammation that has been implicated in the development and progression of cognitive impairment.
Periodontitis stimulates the production of inflammatory cytokines including IL-1, IL-6 and TNF which contribute to an increase in neuroinflammatory responses via haematogenous spreadviii. Platelet aggregation proteins are expressed from the presence of periodontal pathogens including Streptococcus sanguis and P. gingivalis. These play a role in the development of thrombi and atheroma that increase the risk of cognitive decline through vascular dementiaviii.
Evidence establishing the link between oral disease and cognitive decline are still early, however, the numerous available studies demonstrating the presence of oral microorganisms in amyloid beta and contribution of periodontitis to systemic inflammation suggests that periodontal treatment is a modification that could reduce the progression and severity of neurodegenerative diseases.
i. Ryder M, Xenoudi P. Alzheimer disease and the periodontal patient: New insights, connections, and therapies. Periodontology 2000. 2021; 87: 132-142
ii. Australian Bureau of Statistics. "Disability, Ageing and Carers, Australia: Summary of Findings." ABS, 2018, website
iii. Kaye EK, Valencia A, Baba N, Spiro A III, Dietrich T, Garcia RI. Tooth loss and periodontal disease predict poor cognitive function in older men. J Am Geriatr Soc. 2010;58(4):713-718.
iv. Stewart R, Weyant RJ, Garcia ME, et al. Adverse oral health and cognitive decline: the health, aging and body composition study. J Am Geriatr Soc. 2013;61(2):177-184
v. Iwasaki M, Kimura Y, Ogawa H, et al. Periodontitis, periodontal in-flammation, and mild cognitive impairment: a 5-year cohort study. J Periodontal Res. 2019;54(3):233-240
vi. Kamer AR, Craig RG, Niederman R, Fortea J, de Leon MJ. Periodontal disease as a possible cause for Alzheimer's disease. Periodontol 2000. 2020;83(1):242-271
vii. Guo, H.; Chang, S.; Pi, X.; Hua, F.; Jiang, H.; Liu, C.; Du, M. The Effect of Periodontitis on Dementia and Cognitive Impairment: A Meta-Analysis. Int. J. Environ. Res. Public Health 2021, 18, 6823
viii. Nascimento PC, Castro MML, Magno MB, Almeida APCPSC, Fagundes NCF, Maia LC and Lima RR (2019) Association Between Periodontitis and Cognitive Impairment in Adults: A Systematic Review. Front. Neurol. 10:323.