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Title A Significant Association Exists Between Periodontal Disease and Alzheimer’s Disease
Clinical Question Is a patient with periodontal disease at higher risk of developing Alzheimer’s disease, compared to an individual without periodontal disease?
Clinical Bottom Line A significant association exists between periodontitis and Alzheimer’s disease, proposing that patients with periodontal disease are at higher risk of developing Alzheimer’s disease. This proposal is supported by a systematic review and robustly powered retrospective matched-cohort study. Based on the findings of these references, it can be postulated that patients with severe periodontitis who have been exposed to the disease for a minimum of 10 years are at greatest risk for developing Alzheimer’s disease.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 28219071Leira/2017982 adult patients in 5 included studies; 5/5 studies included in SR; 3/5 included in meta-analysisSystematic review of non-randomized trials
Key resultsThis systematic review and meta-analysis investigated the association between periodontal disease (PD) and Alzheimer’s disease (AD). The study designs included in this review are two cross-sectional studies, two case-control studies and one cohort study. The review determined that a significant association exists between PD and AD. The meta-analysis verified this association, taking into account the different forms of periodontitis. The collective odds ratio (OR) for all forms of PD was 1.69 (95% CI: 1.21-2.35). This OR value was found for moderate periodontitis as well, and an even stronger association was found for severe periodontitis and AD (OR=2.98, 95% CI: 1.58-5.62).
#2) 28784164Chen/20179,291 patients with CP; 18,672 patients without CP Cohort study
Key resultsThis retrospective matched (age, sex, co-morbidity, index year and urbanization level) cohort study evaluated if patients with chronic periodontitis (CP) are at an increased risk of developing Alzheimer’s disease (AD). The study evaluated 16 years of data from the National Health Insurance Program in Taiwan. In addition to periodontitis, AD-related co-morbidities (HTN, hyperlipidemia, chronic kidney disease, depression, stroke, diabetes mellitus and traumatic brain injury) were assessed. A statistically significant difference was found with regards to risk of developing AD, between the group with CP and the group without CP, after a 10-year period of exposure to the disease (p=0.0264 by log-rank test). These results led to the finding that a significant association exists between CP and AD following 10 years of exposure to CP (adjusted HR=1.701, p=0.0077), irrespective of co-morbidities and urbanization level.
Evidence Search "Periodontitis"[Mesh] AND "Alzheimer Disease"[Mesh]
Comments on
The Evidence
Although the systematic review and meta-analysis only included five studies, the review protocol was robust in that the ad hoc review group included three neurologists, four periodontists and one epidemiologist. The systematic search included hand searching through peer-reviewed dental and medical journals, and reputable electronic databases. The inter-examiner agreement between the two reviewers had a kappa score of 0.82, with any discrepancies settled by a third examiner. A limitation of the study was that no definitive criteria (clinical parameters) for the diagnosis of periodontal disease was established among the included studies. The Chen article included a large study sample over an extended period of time; however, the data only included patients of Taiwanese descent. Interpretation of the results must be held with reservation since the data was limited to only one patient population. Both studies pointed out that a “bidirectional relationship” exists between the two diseases and must be considered. Patients with AD typically do not possess the cognitive or physical ability to perform proper oral hygiene, therefore predisposing them to periodontal disease.
Applicability Due to the increasing life expectancy of our patients and chronic nature of both periodontal and Alzheimer’s disease, dental providers will be confronted with both conditions. Therefore, it is imperative that we understand the association between the diseases. Currently, it has been proposed that an indirect and direct pathway exists linking the two diseases. Pro-inflammatory cytokines released as a response to periodontal pathogens in dental biofilms enter the systemic circulation and reach the brain. This causes chronic neuroinflammation and neurodegenerative changes of the brain tissue, leading to Alzheimer’s disease (indirect pathway). Furthermore, virulent periodontal pathogens (P. Gingivalis, T. forsythia, A. actinomycetemcomitans and T. denticola) themselves can travel to the brain via peripheral nerves or enter the bloodstream at the ulcerated sulcular epithelium (periodontal pocket). Once they enter the brain, they directly invade the neural tissue causing chronic neuroinflammation that leads to the plaque formations associated with Alzheimer’s disease.
Specialty/Discipline (General Dentistry) (Periodontics)
Keywords Periodontal disease, Alzheimer’s disease
ID# 3403
Date of submission: 11/21/2019spacer
E-mail casarezquint@uthscsa.edu
Author Alicia Casarez-Quintana, DDS
Co-author(s) Pei Wang
Co-author(s) e-mail wangp1@livemail.uthscsa.edu
Faculty mentor/Co-author Dr. Richard Finlayson, DDS
Faculty mentor/Co-author e-mail finlaysonr@uthscsa.edu
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