Losing memories of loved ones is one of the biggest fears many people have. Unfortunately, this fear turned into reality for 44 million people worldwide. This neurological disorder, particularly Alzheimer's Disease (AD), destroys the memory and cognitive abilities of people, especially as they grow older. Despite millions of people have suffered from this disease for centuries, there is still no cure. While most people would assume that all the secrets to the cure are hidden in the brain, they can actually be found all over our body, including the oral cavity.
Kyeong Hee Lee and Yoon Young Choi, associated with the Department of Dental Hygiene in Shinhan University, studied the correlation between the oral health of the elderly and dementia. Through their research, the authors concluded that periodontal disease—infection of the gum that leads to inflammation—is a potential risk factor for dementia (Lee & Choi 5).
Although the data demonstrate that there is a possible correlation, an actual analysis of how gum diseases can cause AD remains a question. One hypothesis that some scientists propose is that the bacteria and inflammation from periodontitis worsen the inflammation in the central nervous system, furthering the progression of dementia (National Institute of Health). According to recent studies, neurodegeneration can occur when there is systemic inflammation due to the activation of the microglia, immune cells of the central nervous system, and the release of pro-inflammatory cytokine (Liccardo et al. 7). Furthermore, previous research has shown that bacteria induce neuroinflammation, which contributes to the development of AD.
Figure 1:Poor oral health may be linked to Alzheimer’s Disease.
Source Credit: Advance Dental PC (LINK)
Based on this knowledge, Liccardo et al. proposed a mechanism of how periodontitis induces AD, represented in Figure 1. In Step 1, oral dysbiosis—an imbalance of bacteria in the mouth—causes certain types of bacteria to invade the tissue and bloodstream. Then in Step 2, the oral pathogens bind to the microglia which, in Step 3, releases cytokines and inflammatory mediators. Ultimately, more Amyloid-ß peptides (Aßp)—a protein that contributes to neural growth and repair but destroys nerve cells later in life when misfolded—are secreted in Step 4. Finally, Step 5 demonstrates that the Aßps form amyloid plaques that bind to the receptors of microglia, producing even more Aßps and subsequently, neurofibrillary tangles (p-tau tangles) as well (Liccardo et al. 7). This process leads to neurodegeneration because the accumulation of amyloid plaques and p-tau tangles prevent the neurons from proper function.
Some scientists agree with this hypothesis and mechanism, while others, like Yi-Qian Sun and associates, believe the contrary: that periodontitis has no relationship with AD. With the two-sample Mendelian randomization (MR) approach, the team reached the conclusion that there is not enough evidence suggesting that AD is caused by periodontitis.
Furthermore, scientists still have questions such as “Does periodontitis cause neurodegeneration or vice versa?” and “What are the different ways gum disease induces the development of AD?” For example, another hypothesized way that poor oral health could cause dementia is malnutrition. One of the main symptoms of inflammatory disease is teeth loss, particularly for the elderly. As a result, the ability to chew is impaired, which could hinder the consumption of essential nutrients and possibly cause the progression of AD (Dioguardi et al. 1-2).
Despite hundreds of scientists studying the relationship between oral health and AD, much is still unknown. Scientists hope that if more information about this relationship could be discovered, humans would be one step closer to finding a cure for this neurodegenerative disease. Then, the millions of people who have or will have this disease will not have the experience of the pain of losing their loved ones.
Q&A:
Jennah: Are there diseases other than AD linked with oral health? Or is this a potential relationship exclusive to mental disorders?
Oral health is linked with various diseases other than AD. For example, poor oral health could lead to diabetes, heart disease, and stroke. However, this relationship could be viewed from a different perspective, such as diabetes signifying worsened oral health due to unhealthy food consumption.
Anna: What exactly is the Mendelian randomization approach? How does it work?
The Mendelian randomization approach is a method of using genetic variations as variables to observe the causal relationship between risk factors and health outcomes. The scientists I mentioned in the article used this approach to find evidence that poor oral health leads to AD. However, there are many other approaches that scientists used to find their relationship, and the Mendelian randomization approach is just one example.
David: How does lack of nutrition lead to the progression of AD? Is there also a correlation there and are there studies to also back up that hypothesis?
Multiple studies have shown that lack of nutrition contributes to the progression of dementia. For example, a lack of Vitamin D in the blood is known to cause AD. However, AD is not developed just because you lack nutrients; in most cases, it is the accumulation of multiple health conditions, including lack of nutrients and oral disease. Therefore, lack of nutrients alone won’t necessarily lead to AD being developed but it could be one of the many factors.
Ian: Should we be concerned that periodontal disease could lead to a neurological disease or inflict damage to our nervous system?
Currently, there is no research that shows that periodontal pathogens can directly inflict damage to our nervous system. However, it could weaken the blood-brain barrier (a protective network of tissues and blood vessels that surround the brain) and increase the risk of neurological diseases. Thus, I would say you don’t have to be worried too much about it but still pay more attention to your oral health to prevent potential harm.
John: Could you give a brief summary of what is happening in the image you used in the article?
In summary, the image is showing pathogens from the oral disease invading the bloodstream and causing amyloid plaques to be formed in neurons. Amyloid plaques are proteins that destroy the nerve cell.
Melissa: Are other diseases associated with oral health also related to AD? If so, what is causing this correlation?
Most oral diseases are known to cause the progression of AD because of the invasion of pathogens impairing the nerve cells. But another way oral disease could be related to AD is the lack of nutrients, as mentioned in the article.
Works Cited
Beydoun, May A., et al. "Clinical and Bacterial Markers of Periodontitis and Their Association with Incident All-Cause and Alzheimer's Disease Dementia in a Large National Survey." Journal of Alzheimer's Disease, vol. 75, no. 1, 5 May 2020, pp. 157-72, https://doi.org/10.3233/JAD-200064.
Dioguardi, Mario, et al. "The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer's Disease: A Systematic Review." Journal of Clinical Medicine, vol. 9, no. 2, 11 Feb. 2020, p. 495, https://doi.org/10.3390/jcm9020495.
“Gum Disease Link to Faster Decline in Alzheimer's.” Alzheimer's Society, 1 Oct. 2021, https://www.alzheimers.org.uk/research/care-and-cure-research-magazine/gum-disease-link-faster-decline-alzheimers.
Lee, Kyeong Hee, and Yoon Young Choi. "Association between Oral Health and Dementia in the Elderly: A Population-based Study in Korea." Scientific Reports, vol. 9, no. 1, 8 Oct. 2019, https://doi.org/10.1038/s41598-019-50863-0.
Liccardo, Daniela, et al. "Potential Bidirectional Relationship between Periodontitis and Alzheimer's Disease." Frontiers in Physiology, vol. 11, 3 July 2020, https://doi.org/10.3389/fphys.2020.00683.
Sun, Yi-qian, et al. "Mixed Evidence for the Relationship between Periodontitis and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study." PLOS ONE, vol. 15, no. 1, 24 Jan. 2020, p. e0228206, https://doi.org/10.1371/journal.pone.0228206.
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