Keep your mouth healthy: Gum disease and Alzheimer’s disease

The association between cognitive function and oral health has been well documented so far by some observational studies. On the one hand it has been reported that periodontal disease and tooth loss are associated with increased risk of dementia. On the other hand, improved memory after dental intervention has also  been observed. 

Those findings started the discussion about what would come first: Does initial cognitive decline lead to poor oral hygiene and dental loss, followed by poor nutrition, including decreased intake of vitamins, which would precipitate dementia? Or does periodontal disease increase concentrations of circulating inflammatory markers that might be involved in the pathogenesis of dementia?

Recently, this relationship has become clearer, with the characterization of Amyloid β (Aβ) as an antimicrobial peptide. Chronic periodontitis and infection with Porphyromonas gingivalis – a keystone pathogen in the development of chronic periodontitis – are significant risk factors for developing Aβ-plaques, dementia and AD. 

In a study published in Science Advances (1), a multinational team of investigators found that the presence of oral P gingivalis infection in mice resulted in brain infiltration by the bacteria, what was followed by increased production of Aβ, the component of amyloid plaques implicated in AD. They also found that AD brains showed a greater immunoreactivity to gingipains – a virulence factor produced by P gingivalis – than brains of non-AD control groups . Moreover, DNA from P gingivalis was found in the cerebral spinal fluid (CSF) of living AD patients and in postmortem studies of AD patients.

These findings offer evidence that brain infection with P gingivalis is not a result of poor dental care following the onset of dementia or a consequence of late-stage disease, but an early event that can explain the pathology found in middle aged individuals before cognitive decline. 

It supports the concept that Aβ is an antimicrobial peptide and reinforces the importance of maintaining a healthy microbiome to prevent AD.

Once the oral cavity is infected, P gingivalis may access the brain via a number of pathways including: 1) infection of monocytes followed by brain recruitment, 2) direct infection and damage to endothelial cells protecting the blood-brain barrier, and/or 3) infection and spreading through cranial nerves [e.g., olfactory or trigeminal] to the brain. 

After entering the brain, it modulates inflammatory innate and adaptive immune responses and activates the Aβ inflammatory cascade (see section causes for further information) with production of Aβ-plaques. 

Treating chronic periodontitis and P gingivalis infection with antibiotics or using a gingipain inhibitor could reduce the inflammatory response and brake Aβ-plaques formation. But the whole problem would reappear in case of a new episode of P gingivalis infection. 

Conclusion:

The most important factor here is to keep a strong and healthy oral microbiome, which can prevent dysbiosis and assure the balance of oral cavity immune system. Who would have thought that a clean toothbrush and a proper oral hygiene (without too much fluoride) helps to stay mentally fit?

References:

Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333. https://www.ncbi.nlm.nih.gov/pubmed/30746447

Yamamoto T, Kondo K, Hirai H, et al. Association between self-reported dental health status and onset of dementia: a 4-year prospective cohort study of older Japanese adults from the Aichi Gerontological Evaluation Study (AGES) Project. Psychosom Med 2012; April 74 (3): 241-8 https://www.ncbi.nlm.nih.gov/pubmed/22408130

Wu B, Fillenbaum GG, Plassman BL, Guo L. Association Between Oral Health and Cognitive Status: A Systematic Review [published correction appears in J Am Geriatr Soc. 2016 Aug;64(8):1752]. J Am Geriatr Soc. 2016;64(4):739–751. https://www.ncbi.nlm.nih.gov/pubmed/27037761

Harding A, Robinson S, Crean S, Singhrao SK. Can better management of periodontal disease delay the onset and progression of Alzheimer’s disease? J Alzheimers Dis. 2017; 58 (2):337-348 https://www.ncbi.nlm.nih.gov/pubmed/28453484