Schwahn C, Frenzel S, Holtfreter B, et al. Effect of periodontal treatment on preclinical Alzheimer’s disease—results of a trial emulation approach. Alzheimers Dement. 2021 May 29. doi: 10.1002/alz.12378. Online ahead of print.
A simulated controlled clinical trial was performed using recently developed statistical models that allowed combining data from treated and untreated patients from 2 different population cohorts.
Data from 409 untreated participants from the Study of Health in Pomerania (SHIP), a cohort followed since 1997 to track the influence of dental diseases on general health, were combined with data from 177 patients treated periodontally in the Greifswald GANI-MED study. All patients were younger than 60 at the time of their MRI examination. Periodontal treatment for participants in the active group occurred a mean of 7.3 years before the MRI exam.
Study Medication and Dosage
The 177 patients from the Greifswald GANIMED study were treated for periodontal disease following standard of care. All participants were accessed for Alzheimer’s disease via magnetic resonance imaging (MRI).
MRI was used as an indicator of the onset of Alzheimer’s disease.
Periodontal treatment carried out by a dentist specializing in gum disease was associated with a significant reduction in loss of brain matter. Periodontal treatment had a favorable effect on AD-related brain atrophy (-0.41; 95% CI: -0.70 to -0.12; P=0.0051), which corresponds to a shift from the 50th to the 37th percentile of the outcome distribution.
Alzheimer’s disease (AD) is the most common form of dementia. The disease was first described in 1906 by German psychiatrist and neuroanatomist Alois Alzheimer after examining the brain of a woman who had suffered from severe memory loss and behavioral disturbances prior to death.1 It is now estimated that about 27 million people worldwide suffer from AD.
Other diseases may cause dementia as well. After AD, the most common are cerebrovascular dementia, Lewy body dementia, and frontotemporal dementia. The total toll of these diseases is enormous. It is estimated that 44 million people in the world are now suffering from dementia. Treatment costs in the United States alone exceed $600 billion per year.2
Alzheimer’s disease has 2 distinctive characteristics: the deposition of extracellular amyloid β (Aβ) and abnormally phosphorylated Tau in nerve cells. Although drugs targeting amyloid β have been developed, trial results have so far not been satisfactory in changing the disease. This failure has brought the classic amyloid cascade hypothesis into question. Attention has shifted toward a new hypothesis, one that suggests chronic inflammation and microbial infection of the brain lead to Alzheimer’s disease. Suspicion has fallen specifically on Porphylomonas gingivalis, the bacteria that are responsible for periodontic infection. These bacteria have been detected in the brain tissue of AD patients. Experiments on mice suggest that P gingivalis might be causative.3
Proving that this is true in humans is a challenge. These 2 diseases, AD and periodontitis, share many risk factors in common, including age, obesity, smoking, diabetes, alcohol, depression, stress, and education level. Cognitive decline also raises risk for poor oral hygiene, so people with AD tend to have more periodontal disease.4,5 Sorting through this tangle of associations and relationships has made discerning causation from association difficult. The greatest challenge to clarifying the relationship though is ethical. One cannot ethically withhold a medical intervention, in this case dental care, when doing so may cause disease, in this case periodontal disease and possibly Alzheimer’s disease.
These findings strongly suggest that a timely intervention and treatment of periodontal disease can have a significant benefit in future years.
This ethical necessity has left us to rely on observational studies. This current study by Schwahn et al closely emulates a clinical trial and may be as close as we get to a randomized clinical trial to test the hypothesis that P gingivalis causes AD.
The statistical models employed in this study allowed data from treated and untreated people who were participants in 2 different studies to be pooled together, allowing individuals in the SHIP cohort to serve as the control group. Participants in both cohorts live in the same distinct region of Germany.
The relative youthfulness of the participants in these 2 cohorts at the start of the study is worth noting. Given that the participants were younger than 60 at the time of their MRI exams and their dental exams were more than 7 years earlier, we are looking at the impact of an intervention performed in people in their early 50s.
These findings strongly suggest that a timely intervention and treatment of periodontal disease can have a significant benefit in future years. It reinforces our understanding of whole-body medicine and reminds us that in many circumstances we need to act as teammates with other healthcare providers. In this instance, actively getting our patients to see dentists and dental hygienists is good preventive medicine.
We may be able to offer our patients some suggestions to maximize the benefit of treatment. A paper by Rowinska and colleagues published in March 2021 may serve as a resource on how pathogenic microorganisms cause oral diseases and may be especially useful as it details the influence various dietary components have on the disease process. The authors pay particular attention to how diet affects biofilm formation and make suggestions for diets that may decrease biofilm and the subgingival plaque that cause periodontitis.6
While specific diets may reduce biofilm formation, they do not remove it. Biofilm adheres to the teeth tightly and cannot be rinsed away. Physical removal is required either with a toothbrush or dental tools. Thus, no matter how compliant your patient is with diet and supplements, this will not replace the need for dental treatment.
The diet Rowinska and colleagues suggest isn’t that far from what we generally consider a healthy diet—a diet that avoids simple sugars and refined carbohydrates while emphasizing vegetables and fresh fruit and that is high in antioxidants, essential fats, fiber, and collagen.7,8 As far as specific nutritional supplements, Rowinska et al suggest coenzyme Q10, green tea, and quercetin.9,10
People with high levels of stress and poor coping skills have twice as many periodontal diseases as people with minimal stress and good coping skills. There is a relationship between cortisol levels and the degree of periodontal disease.11,12 While reduction of pathogens remains key to controlling periodontal disease, reducing stress may be as or nearly as important. Oxidative stress may have just as important a role as emotional stress on periodontal disease.13 We should already be aware that stress is associated with Alzheimer’s disease. Americans living under high psychological distress are nearly twice as likely to die of Alzheimer’s disease than those with lower stress levels.14
A Mediterranean diet and exercise may be helpful in preserving cognitive function.15 The idea that such lifestyle interventions may also improve periodontal disease is quite plausible and has been examined but not definitively proven.16,17 One such analysis did suggest that consuming olive oil may lower risk of periodontitis.18 Chewable probiotic lozenges in addition to physical plaque removal have been reported to improve periodontal disease.19 What we offer as naturopathic doctors certainly may be helpful but alone does not appear sufficient.20
This study by Schwahn et al adds to the knowledge that suggests periodontal disease contributes strongly to the development of Alzheimer’s disease and that early intervention to prevent periodontal disease can also decrease incidence of AD. A healthy diet helps, and certain supplements may be useful. But routine dental checkups and proper oral hygiene performed by the patient may be the foundation of prevention.
- Hippius H, Neundörfer G. The discovery of Alzheimer's disease. Dialogues Clin Neurosci. 2003;5(1):101-108.
- Alzheimer's Association. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016 Apr;12(4):459-509.
- Matsushita K, Yamada-Furukawa M, Kurosawa M, Shikama Y. Periodontal disease and periodontal disease-related bacteria involved in the pathogenesis of Alzheimer's disease. J Inflamm Res. 2020;13:275-283.
- Wu B, Fillenbaum GG, Plassman BL, Guo L. Association between oral health and cognitive status: a systematic review. J Am Geriatr Soc. 2016;64(4):739-751.
- Genco RJ, Borgnakke WS. Risk factors for periodontal disease. Periodontol 2000. 2013;62(1):59-94.
- Rowińska I, Szyperska-Ślaska A, Zariczny P, Pasławski R, Kramkowski K, Kowalczyk P. The influence of diet on oxidative stress and inflammation induced by bacterial biofilms in the human oral cavity. Materials (Basel). 2021;14(6):1444.
- Dodington DW, Fritz PC, Sullivan PJ, Ward WE. Higher intakes of fruits and vegetables, beta-carotene, vitamin C, alpha-tocopherol, EPA, and DHA are positively associated with periodontal healing after nonsurgical periodontal therapy in nonsmokers but not in smokers. J Nutr. 2015;145(11):2512-2519.
- Woelber JP, Bremer K, Vach K, et al. An oral health optimized diet can reduce gingival and periodontal inflammation in humans—a randomized controlled pilot study. BMC Oral Health. 2016;17(1):28.
- Manthena S, Rao MV, Penubolu LP, Putcha M, Harsha AV. Effectiveness of CoQ10 oral supplements as an adjunct to scaling and root planing in improving periodontal health. J Clin Diagn Res. 2015;9(8):ZC26- ZC28.
- Yelins’ka AM, Liashenko LI, Kostenko VO. Quercetin potentiates antiradical properties of epigallocatechin-3-gallate in periodontium of rats under systemic and local administration of lipopolisaccharide of salmonella typhi. Wiad Lek. 2019;72(8):1499-1503.
- Pitzurra L, Loos BG. Stress en parodontitis [Stress and periodontitis]. Ned Tijdschr Tandheelkd. 2020;127(6):358-364.
- Yu Q, Hu F, Zhu T. [Correlation between salivary stress markers and clinical parameters of periodontitis]. Shanghai Kou Qiang Yi Xue. 2020;29(1):93-96.
- Sczepanik FSC, Grossi ML, Casati M, et al. Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way. Periodontol 2000. 2020;84(1):45-68.
- Singh GK, Lee H. Psychological distress and Alzheimer's disease mortality in the United States: Results from the 1997-2014 National Health Interview Survey-National Death Index Record Linkage Study. J Aging Health. 2021;33(3-4):260-272.
- Hardman RJ, Meyer D, Kennedy G, Macpherson H, Scholey AB, Pipingas A. Findings of a pilot study investigating the effects of Mediterranean diet and aerobic exercise on cognition in cognitively healthy older people living independently within aged-care facilities: the Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study. Curr Dev Nutr. 2020 Apr 18;4(5):nzaa077.
- El-Shinnawi U, Soory M. Actions of adjunctive nutritional antioxidants in periodontitis and prevalent systemic inflammatory diseases. Endocr Metab Immune Disord Drug Targets. 2015;15(4):261-276.
- Martinon P, Fraticelli L, Giboreau A, Dussart C, Bourgeois D, Carrouel F. Nutrition as a key modifiable factor for periodontitis and main chronic diseases. J Clin Med. 2021;10(2):197.
- Iwasaki M, Ennibi OK, Bouziane A, et al. Association between periodontitis and the Mediterranean diet in young Moroccan individuals. J Periodontal Res. 2021;56(2):408-414.
- İnce G, Gürsoy H, İpçi ŞD, Cakar G, Emekli-Alturfan E, Yılmaz S. Clinical and biochemical evaluation of lozenges containing Lactobacillus reuteri as an adjunct to non-surgical periodontal therapy in chronic periodontitis. J Periodontol. 2015;86(6):746-754.
- Laiola M, De Filippis F, Vitaglione P, Ercolini D. A Mediterranean diet intervention reduces the levels of salivary periodontopathogenic bacteria in overweight and obese subjects. Appl Environ Microbiol. 2020;86(12):e00777-20.