What’s the Connection Between Oral Health and Brain Health?

Conceptually, the oral-systemic link is not new. Existing research illustrates the undeniable association between periodontitis and other systemic diseases; however, this research has recently expanded into the potential interface of oral pathogens and the exacerbation of Alzheimer disease (AD) and Alzheimer disease–related dementia (ADRD). The prevalence of this fatal disease and its devastating impact on lives and families only strengthens the urgency of finding ways to fight something that presently has no cure.

We aim to recognize the incidence of AD and ADRD in the United States, to understand the biological pathway in which periodontal pathogens can exacerbate degenerative changes in the brain, and to identify the role of dental professionals in promoting the importance of professional and daily oral care to mitigate disease risk. Periodontal disease is treatable, and we are situated ideally to treat, educate, and promote evidence-based therapeutic interventions to sustain oral health and mitigate the risk of systemic disease.

What Is Alzheimer Disease?

The strong prevalence of AD has touched many of our lives. It takes an emotional toll that is almost impossible to articulate. We see our loved ones become someone so unfamiliar to us, making the loss even more devastating. The research on the connectivity between oral health and brain health is growing rapidly.

Before we delve into the research surrounding periodontal pathogens and the deterioration of brain health, specifically AD, we must understand the disease itself. AD and ADRD are progressive neuroinflammatory and neurodegenerative diseases of the brain. The disease was named after the medical doctor who first discovered it over a century ago, Alois Alzheimer.

Ranking as the seventh leading cause of death in the United States, AD is estimated to impact more than 6 million Americans. Those who are 65 years and older are most at risk, and by 2050, Americans living with the illness could double, barring any medical developments or cures.^1,2

AD is fatal, as there is presently no cure for the disease. The terms Alzheimer disease and dementia are often misunderstood. The brain changes associated with AD are the most common contributors to dementia, accounting for 60% to 80% of cases.^3,4 Dementia is an overall term for a collection of particular symptoms, including memory loss and decline of cognitive skills.

Despite years of research, no one knows the ultimate cause. The deterioration within the brain leading to AD can begin many years before symptoms emerge. Early symptoms may include lack of remembrance of conversations, events, or names. As AD further progresses, impaired communication, disorientation, confusion, behavioral changes, and poor judgment become apparent. The continuance of damage into other parts of the brain eventually impacts organ function and motor skills, making simple activities, such as swallowing or walking, very challenging.⁵ AD is an all-encompassing neurodegenerative, insidious disease.⁶

The pathologic pathway of AD has 3 major trademarks: the accumulation of β-amyloid plaques, neurofibrillary tangles, and neuroinflammation.^7,8 The combination of β-amyloid plaques accumulating outside of neurons and the tangled strands of proteins inside neurons results in heightened inflammation and neuron death.

What Is the Connection With Oral Health?

As periodontal disease develops, sulcular wounds in the epithelium serve as a portal of entry for pathogens to travel to the brain. Simple daily tasks, such as brushing, flossing, and even chewing, can access the portal of entry pathway.⁹ Recent studies direct our attention to Porphyromonas gingivalis, a leading culprit in the exacerbation of periodontal disease, being the link between these 2 inflammatory and degenerative conditions.^10,11 P gingivalis can colonize in the brain, causing damage to brain neurons and contributing to the production of β-amyloid plaques.6 Furthermore, toxic enzymes called gingipains are released by P gingivalis. Gingipains belong to a group of specific proteinases recognized as major virulence factors found in inflamed gingival tissues of individuals with periodontal disease. Gingipains have also been found in 96% of brain samples from deceased patients with AD and in the cerebrospinal fluid of living patients, according to study results reported in 2019 in Science Advances.¹²

The research revealed that the pathogenesis of AD appears to be directly related to both secretion and load of gingipains, resulting in neuronal damage.12 Of particular interest was the location of the concentration of gingipains; they were most prominent in the hippocampus, which is one of the primary regions associated with memory.¹² The investigators also noted that the amount of gingipains tended to rise over time, suggesting a tipping point when dementia symptoms first begin.¹²

At present, there are very limited pharmaceuticals currently approved to treat AD. The objective of present pharmaceuticals is to target the protein β-amyloid to reduce the amyloid plaques. However, this approach is not addressing the root etiologic pathway. A new breakthrough presently in animal studies is designed to inhibit gingipain invasion and resulting neuronal damage.13 Pretreatment of mice with gingipain inhibitors protected the hippocampal neurons from the neurotoxic impact of gingipains. In turn, this reduces the P gingivalis load and β-amyloid buildup.¹³ Conversely, broad-spectrum antibiotics and specific β-amyloid medications did not protect the brain cells from the toxic effects of P gingivalis.¹³ These more recent findings suggest a new conceptual framework for both treating and mitigating risk for the disease.¹³

What Can We Do as Dental Professionals?

As dental professionals, we are not powerless in our ability to make an impact on this insidious disease. Per the Scientific American, “poor oral health is both common and treatable and could lead to a new paradigm for prevention that includes optimal oral care.”¹ Helping our patients understand the critical importance of optimal oral health is key. There are several initiative-taking strategies that we may employ.

Our risk assessments overlap with a variety of modifiable risk factors that exacerbate the progression of AD. This is where the intersection of prevention and education can reach the public in ways other health care providers may not. Taking medical history can be instrumental in educating patients on how these factors may elevate risk for AD and ADRD. Supportive science directs our attention to the fact that AD is associated with many systemic diseases and lifestyle behaviors. These include cardiovascular disease, diabetes, chronic inflammatory pathogens, smoking, and sleep patterns.¹⁴

One person dies every 34 seconds in the United States from cardiovascular disease; it is the leading cause of death.¹⁵ The taking of blood pressure readings at a dental appointment is a powerful opportunity to uncover a silent killer—hypertension. Studies also illustrate that elevated blood pressure in middle age results in drastic increases in dementia risk later in life.¹⁶

Chairside testing can play a vital role in prediabetes and diabetes diagnosis, which would have otherwise gone undetected.¹⁷ Point-of-care testing for blood glucose levels has become far more commonplace in dental practices. The American Dental Association added a current dental terminology (CDT) code, D0411, for chairside HbA1c, and in 2019, the association added CDT code D0412 to check blood glucose levels. Findings suggest that individuals with type 2 diabetes or a form of metabolic glucose disorder may have a predisposition for predementia or a mild cognitive impairment. In fact, individuals with elevated blood glucose levels, irrespective of diagnosed disease, have a faster cognitive decline rate.^18-20 Research is also focused on a new type of diabetes, type 3, which is correlated with AD.

The reduction of the burden of chronic inflammation is integral to mitigating risk for systemic disease. A proactive treatment approach begins with adjusting the interval of care to meet the needs of the patient. The following may comprise part of our treatment plan:

• Chairside antimicrobial/pathogen testing
• Antimicrobial rinses (eg, chlorhexidine, povidone-iodine)
• Systemic antibiotics
• Localized antibiotic delivery
• Chlorhexidine in a gelatin matrix
• Laser decontamination to delay pathogenic colonization
• Attainment of a balanced oral microbiome with oral probiotics

Lifestyle behaviors are also strong contributors to the disease process. Helping our patients understand modifiable risk factors can be very empowering and lead to more positive choices regarding behaviors. Smoking and its known toxins increase oxidative stress and contribute to inflammation known to be associated with AD. A 2017 study concluded that smoking increased the incidence of dementia later in life. Educating our patients of the association with AD and ADRD and directing them to smoking cessation programs is a tangible way to address another modifiable risk factor.²¹

Dentistry has become far more proactive in identifying sleep apnea through identification of symptoms. Once assessed, the patient is 1 step closer to diagnosis and subsequent referral to a specialist. A 2013 study found that adults who experienced poor or fragmented sleep patterns were more prone to develop AD.²² Conversely, research has identified that healthy sleep patterns contribute to decreasing amyloid accumulation and increasing amyloid clearance from the brain.²³

Effective daily self-care strategies are imperative in reducing the oral inflammatory response and managing a healthy oral biofilm. As dental professionals, we wish to provide recommendations that are both effective and supported by strong science. It is a well-known fact that power toothbrushes deliver a statistically superior result than manual toothbrushes. Chairside trial programs are a powerful way to introduce patients to the benefits of power toothbrushing, clarify any misconceptions, and assist with proper technique. A literature search conducted in PubMed concluded that high-quality flossing is difficult to achieve. Ineffective flossing routines by much of the population are not providing any significant benefits over brushing alone. Interdental brushes are more effective than brushing alone and superior to flossing in widened embrasures. Oral irrigators hold the most promise for reducing inflammatory markers and accessing subgingival pocket depths. There are several innovative devices on the market today, and it is important to play a supportive role in the day-to-day oral care practices of our patients.

As dental professionals, we have the highest gratification any human being can have, and that is to serve others. There are many opportunities for dental professionals to play a part in diminishing the risk for AD and ADRD. Periodontal disease is treatable, and we are ideally positioned to raise awareness, educate, and promote evidence-based therapeutic interventions.

References

1. Chronic gum disease may harm brain, joints and gut. Scientific American. Accessed February 2, 2023. https://www.scientificamerican.com/custom-media/healthy-mouth-healthy-body/chronic-gum-disease-may-harm-brain-joints-and-gut/

2. 2022 Alzheimer’s disease facts and figures. Alzheimers Dement. 2022;18(4):700-789. doi:10.1002/alz.12638

3. Dementia vs. Alzheimer’s disease: what is the difference? Alzheimer’s Association. Accessed February 2, 2023. https://www.alz.org/alzheimers-dementia/difference-between-dementia-and-alzheimer-s

4. Stages of Alzheimer’s. Alzheimer’s Association. Accessed February 2, 2023. https://www.alz.org/alzheimers-dementia/stages

5. Tom SE, Hubbard RA, Crane PK, et al. Characterization of dementia and Alzheimer’s disease in an older population: updated incidence and life expectancy with and without dementia. Am J Public Health. 2015;105(2):408-413. doi:10.2105/AJPH.2014.301935

6. Ryder MI. Porphyromonas gingivalis and Alzheimer disease: recent findings and potential therapies. J Periodontol. 2020;91(suppl 1):S45-S49. doi:10.1002/JPER.20-0104

7. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1(1):a006189. doi:10.1101/cshperspect.a006189

8. Hampel H, Hardy J, Blennow K, et al. The amyloid-β pathway in Alzheimer’s disease. Mol Psychiatry. 2021;26(10):5481-5503. doi:10.1038/s41380-021-01249-0

9. Kumar PS. From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. J Physiol. 2017;595(2):465-476. doi:10.1113/JP272427

10. Mei F, Xie M, Huang X, et al. Porphyromonas gingivalis and its systemic impact: current status. Pathogens. 2020;9(11):944. doi:10.3390/pathogens9110944

11. How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol. 2016;7:53. doi:10.3389/fmicb.2016.00053

12. 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. doi:10.1126/sciadv.aau3333

13. Kanagasingam S, Chukkapalli SS, Welbury R, Singhrao SK. a Strong Risk Factor for Alzheimer's Disease. J Alzheimers Dis Rep. 2020;4(1):501-511. Published December 14, 2020. Accessed February 14, 2023. doi:10.3233/ADR-200250

14. Rice AO. Alzheimer’s disease and oral-systemic health: bidirectional care integration improving outcomes. Front Oral Health. 2021;2:674329. doi:10.3389/froh.2021.674329

15. Heart disease facts. CDC. Updated October 14, 2022. Accessed February 2, 2023. https://www.cdc.gov/heartdisease/facts.htm

16. Lane CA, Barnes J, Nicholas JM, et al. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. Lancet Neurol. 2019;18(10):942-952. Published correction appears in Lancet Neurol. 2020;19(7):e6.

17. Montero E, Matesanz P, Nobili A, et al. Screening of undiagnosed hyperglycaemia in the dental setting: the DiabetRisk study. A field trial. J Clin Periodontol. 2021;48(3):378-388. doi:10.1111/jcpe.13408

18. De Widt L. What is the link between Alzheimer’s and type 3 diabetes? Mayo Clinic News Network. October 25, 2017. Accessed February 2, 2023. https://newsnetwork.mayoclinic.org/discussion/researchers-link-alzheimers-gene-to-type-iii-diabetes/

19. Panza F, Frisardi V, Seripa D, et al. Metabolic syndrome, mild cognitive impairment, and dementia. Curr Alzheimer Res. 2011;8(5):492-509. doi:10.2174/156720511796391818

20. Zheng F, Yan L, Yang Z, Zhong B, Xie W. HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing. Diabetologia. 2018;61(4):839-848. doi:10.1007/s00125-017-4541-7

21. Walker KA, Power MC, Gottesman RF. Defining the relationship between hypertension, cognitive decline, and dementia: a review. Curr Hypertens Rep. 2017;19(3):24. doi:10.1007/s11906-017-0724-3

22. Lim AS, Kowgier M, Yu L, Buchman AS, Bennett DA. Sleep fragmentation and the risk of incident Alzheimer’s disease and cognitive decline in older persons. Sleep. 2013;36(7):1027-1032. doi:10.5665/sleep.2802

23. Winer JR, Mander BA, Kumar S, et al. Sleep disturbance forecasts β-amyloid accumulation across subsequent years. Curr Biol. 2020;30(21):4291-4298.e3. doi:10.1016/j.cub.2020.08.017

About the Author

As a veteran dental hygienist, recognized thought leader, and international, award-winning speaker, Jo-Anne Jones, RDH, has delivered more than 1000 presentations across Canada, the United States, and the United Kingdom. Jones is a 2021 Fellowship Award recipient with the International Academy of Dental Facial Esthetics. Jones is also a past recipient of the Elizabeth Craig Award of Distinction for her exemplary commitment to the dental hygiene profession. Additionally, she was nominated by Dental Products Report® as one of the Top 25 Women in Dentistry in 2013. Jones is a key opinion leader for many leading dental corporations across North America, including Philips Oral Healthcare.