The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Eligibility Criteria
- To include all those studies describing the association between Alzheimer’s disease and periodontal disease.
- To include all articles describing the role of bacteria such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Treponema denticola in the onset and progression of the Alzheimer’s disease.
- To exclude all studies that were not written in English and were published before 1990.
- To exclude non-systematic literature reviews.
2.2. Research Methodology
2.3. Screening Methodology
- (1)
- Primary outcome: associations between periodontitis and Alzheimer’s disease.
- (2)
- Secondary outcome: associations between bacteria involved in the pathogenesis of periodontal disease and Alzheimer’s disease.
3. Results
Study Characteristics and Data Extraction
- First outcome: The articles included for the first outcome (associations between periodontitis and Alzheimer’s disease) after the elimination of overlaps were about a hundred. The articles were then studied to deepen and update the reviewers’ knowledge on the subject of the association between Alzheimer’s disease and periodontitis. Articles were used to draft the discussion on the correlations between the two diseases and their respective etiopathogenesis.
- Second outcome: the articles included for the second outcome (associations between bacteria involved in the pathogenesis of periodontal disease and Alzheimer’s disease) were Wu et al. 2017 [9], Hayashi et al. 2019 [10], Poole et al. 2013 [11], Carter et al. 2017 [12], Liu et al. 2017 [13], Laugish et al. 2018 [14], Ide et al. 2016 [15], Ishida et al. 2017 [16], Dominy et al. 2019 [17], Nie et al. 2019 [18], Diaz-Zuniga et al. 2019 [6], Sparks Stein et al. 2012 [19], Noble et al. 2014 [20], Carter et al. 2017 [21], and Kamer et al. 2009 [22].
4. Discussion
4.1. Periodontal disease
4.2. Alzheimer’s disease
4.3. Inflammatory Theory
4.4. Associative Hypotheses between Periodontitis and Neurodegenerative Diseases: Aspects in Common
4.5. Analysis of the Evidence on the Role of P. gingivalis on the Etiopathogenesis of A.D.
4.6. Health and Oral Hygiene in Patients with Alzheimer’s Disease
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Database—Provider | Key Words | Search Details | Number of Records | Number of Records) after Limiting by Year of Publication (last 30 years) | Number of Studies Dealing with the Topic of Alzheimer’s Disease in Relation to Oral Inflammatory Processes and Bacteria | Number of Articles Investigating the Role of Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease | Articles after Removing Overlaps | Number of Articles Included in the Qualitative Analysis |
---|---|---|---|---|---|---|---|---|
PubMed | “Alzheimer’s Disease” AND “periodontal” | “Alzheimer’s Disease” (All Fields) AND “periodontal” (All Fields) | 96 | 96 | 48 | 7 | ||
PubMed | “Alzheimer’s Disease” AND “periodontitis” | “Alzheimer’s Disease” (All Fields) AND “periodontitis” (All Fields] | 87 | 87 | 56 | 9 | ||
PubMed | “dementia “AND “periodontal” | “dementia “(All Fields] AND “periodontal” (All Fields) | 118 | 117 | 41 | 3 | ||
PubMed | “Alzheimer’s Disease” AND “actinomycetemcomitans” | “Alzheimer’s Disease” (All Fields] AND “actinomycetemcomitans” (All Fields) | 3 | 3 | 3 | 2 | ||
PubMed | “Alzheimer’s Disease” AND “gingivalis “ | “Alzheimer’s Disease” (All Fields) AND “gingivalis” (All Fields) | 34 | 34 | 20 | 20 | ||
PubMed | “Alzheimer’s Disease” AND “denticola “ | “Alzheimer’s Disease” (All Fields) AND “denticola” (All Fields) | 9 | 9 | 7 | 6 | ||
PubMed | “Alzheimer’s Disease” AND “nucleatum” | “Alzheimer’s Disease” (All Fields) AND “nucleatum” (All Fields) | 4 | 4 | 4 | 3 | ||
Scopus | “Alzheimer’s Disease” AND “periodontal“ | TITLE-ABS-KEY (“Alzheimer’s Disease” AND “periodontal”) | 234 | 232 | 84 | 8 | ||
Scopus | “Alzheimer’s Disease” AND “periodontitis” | TITLE-ABS-KEY (“Alzheimer’s Disease” AND “periodontitis”) | 182 | 182 | 48 | 11 | ||
Scopus | “dementia “AND “periodontal” | TITLE-ABS-KEY (“dementia” AND “periodontal”) | 217 | 214 | 71 | 4 | ||
Scopus | “Alzheimer’s Disease” AND “actinomycetemcomitans” | TITLE-ABS-KEY (“Alzheimer’s Disease” AND “actinomycetemcomitans”) | 8 | 8 | 7 | 7 | ||
Scopus | “Alzheimer’s Disease” AND “gingivalis “ | TITLE-ABS-KEY (“Alzheimer’s Disease” AND “gingivalis “) | 64 | 64 | 31 | 19 | ||
Scopus | “Alzheimer’s Disease” AND “denticola “ | TITLE-ABS-KEY (“Alzheimer’s Disease” AND “denticola”) | 20 | 20 | 16 | 9 | ||
Scopus | “Alzheimer’s Disease” AND “nucleatum” | TITLE-ABS-KEY (“Alzheimer’s Disease” AND “nucleatum”) | 12 | 12 | 8 | 6 | ||
Total records | 1088 | 1082 | 444 | 114 | 36 | 15 |
Reviewer 2 | Reviewer 2 | Reviewer 2 | |||
---|---|---|---|---|---|
Include | Exclude | Unsure | Total | ||
Reviewer 1 | include | 15 | 2 | 1 | 18 |
Reviewer 1 | exclude | 0 | 13 | 0 | 13 |
Reviewer 1 | unsure | 1 | 3 | 1 | 5 |
total | 16 | 18 | 2 | 36 |
Author, Data, and Journal | Type of Study | Cell Lines, Tissue, Animals, and Databases | Antibodies, Antigens, Enzyme, and Proteins Investigated | Investigated Microorganisms | Results |
---|---|---|---|---|---|
Wu et al., 2017, Brain Behav Immun [9] | Experimental study on mice and cell lines | (CatB−/−) mice, MG6 microglia cell line, | Pg- LPS, CatB | P. gingivalis | CatB plays a critical role in the link between periodontitis and AD. |
Hayashi et al. 2019, Exp Gerontol [10] | Experimental study on mice | Mice | Pg- LPS | P. gingivalis | LPS pg exposure worsens the prognosis in AD |
Poole rt al. 2013, J Alzheimers Dis [11] | Experimental study on brain tissue and cell lines | Postmortem brain tissue, SVGp12 cells | LPS | T. denticola T. forsythia P. gingivalis | Associative hypothesis between LPS pg and AD |
Carter et al 2017, Journal of Alzheimer’s disease reports [12] | Bioinformatics study on databases | GWAS databases | 78 AD genes (GWAS) | Bacteria, viruses, fungi | The use of antibiotics and antifungals could reduce the effects of AD |
Liu et al. 2017, Sci Rep [13] | Experimental study on mice and cell lines | Mice, MG6 microglia cell line | Arg-gingipain (Rgp) and Lys-gingipain (Kgp) | P. gingivalis | Data supports the infection hypothesis of Alzheimer’s disease |
Laugish et al.2018, J Alzheimers Dis [14] | Clinical study | Patients with dementia (N = 20 in AD and N = 20 dementia non AD) | Tau protein (T-tau) and Amyloid β (Aβ1-42) in CFS(Cerebro spinal fluid) and Antibody levels in CFS e serum | P. gingivalis T. forsythia T. denticola T. socranskii A.actinomycetemcom | The data does not support an associative hypothesis |
Ide et al. 2016, PLoS One [15] | Observational cohort study | Patients with dementia (n = 60) | Serum inflammation, antibody and DNA assays | P.gingivalis | Study suggests there is a direct relationship between periodontitis and cognitive decline |
Ishida et al. 2017, NPJ aging and mechanisms of disease [16] | Experimental study on mice | Mice | Amiloid β (Aβ) deposition, Aβ40, Aβ42, IL-1β and TNF-α | P. gingivalis | Concludes that periodontitis is truly a risk factor for AD |
Dominy et al. 2019, Sci Adv [17] | Prospective pilot study | Mice and AD patients. | (Kgp), (Rgp), P. gingivalis 16S rRNA gene, P. gingivalis DNA in CFS, Aβ1–42 in cerebral mice tissue | P. gingivalis | P. gingivalis and gingipains in the brain play a central role in the pathogenesis of AD |
Nie et al. 2019, J Alzheimers Dis [18] | Experimental study on mice | Mice | IL-1β, AβPP770, CatB, Aβ1-42, and Aβ3-42 in macrophage/monocites | P. gingivalis | Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression. |
Diaz-Zuniga et al. 2019, J Oral Microbiol [6] | Experimental study on cell line rat | Line rat cell (Mixed hippocampal cultures, Microglial cultures) | IL-1β, IL-6, TNF-α and Aβ1-42 | A. actinomycetemcomitans | Probable association between aparodontal disease sustained by Aggregatibacter and AD etiopathology |
Sparks Stein et al. 2012, Alzheimer’s Dement [19] | Longitudinal study | Patient AD = 35, MCI = 46 and control = 76 | Antibody levels | A. actinomycetemcomitans P. gingivalis, C. rectus, T. denticola, Fusobacterium nucleatum, T. forsythia | Possible association between antibody levels and onset and progression of AD |
Noble et al. 2014, PLoS One [20] | Case–cohort study | Patients who developed AD in follow-up | Serum IgG | P. gingivalis, T. forsythia A. actinomycetemcomitans T. denticola, C. rectus, E. nodatum and A. naeslundii | Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD |
Carter et al. 2017, Front Aging Neurosci [21] | Bioinformatics study on databases | GWAS databases | P. gingivalis/host interactome | P. gingivalis | Supports the many documented relationships between P. gingivalis infection and AD or its comorbid conditions |
Kamer et al. 2009, J Neuroimmunol [22] | Observational Study | 18 with AD and 16 cognitively normal | Plasma TNF-α, IL-1β and IL-6 levels, IgG antibody | A. actinomycetemcomitans serotype b, T. forsythia and P. gingivalis | Antibody levels to periodontal bacteria associate with AD and may help improve the clinical diagnosis of AD |
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Dioguardi, M.; Crincoli, V.; Laino, L.; Alovisi, M.; Sovereto, D.; Mastrangelo, F.; Lo Russo, L.; Lo Muzio, L. The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review. J. Clin. Med. 2020, 9, 495. https://doi.org/10.3390/jcm9020495
Dioguardi M, Crincoli V, Laino L, Alovisi M, Sovereto D, Mastrangelo F, Lo Russo L, Lo Muzio L. The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review. Journal of Clinical Medicine. 2020; 9(2):495. https://doi.org/10.3390/jcm9020495
Chicago/Turabian StyleDioguardi, Mario, Vito Crincoli, Luigi Laino, Mario Alovisi, Diego Sovereto, Filiberto Mastrangelo, Lucio Lo Russo, and Lorenzo Lo Muzio. 2020. "The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review" Journal of Clinical Medicine 9, no. 2: 495. https://doi.org/10.3390/jcm9020495