The evidence of a connection between the peripheral inflammatory processes and neurodegenerative diseases of the central nervous system is becoming more apparent. This review of the related literature highlights the most recent clinical, epidemiological, and in vitro studies trying to investigate possible connections between periodontal bacteria and the onset and progression of Alzheimer’s disease. This review was conducted by searching databases such as PubMed and Scopus using keywords or combinations such as Alzheimer’s Disease AND periodontal or dementia AND periodontitis OR periodontal. After eliminating overlaps and screening the articles not related to these issues, we identified 1088 records and proceeded to the selection of articles for an evaluation of the associative assumptions. The hypothesis suggested by the authors and confirmed by the literature is that the bacterial load and the inflammatory process linked to periodontal disease can intensify inflammation at the level of the central nervous system, favoring the occurrence of the disease. The analysis of the literature highlights how periodontal disease can directly contribute to the peripheral inflammatory environment by the introduction of periodontal or indirect pathogenic bacteria and proinflammatory cytokines locally produced at the periodontal level following bacterial colonization of periodontal defects.
Alzheimer’s disease and its consequent cognitive decline represent a severe public health problem, considering the increase of its incidence, the prolongation of the average life expectancy, and its great impact on quality of life. Knowledge of its pathophysiological mechanisms is not sufficient yet, so the preventive approach related to known and/or unknown risk factors could mean a more efficient management of the patient and consequently a better quality of life. Therefore, the present paper aims to evaluate whether there are any aspects of periodontitis that could potentially relate to neurodegenerative disease pathogenesis, thus representing a risk factor; this could be relevant because nowadays, periodontitis is fully treatable and preventable. This literature review evaluated the contribution of periodontitis to peripheral inflammation through a direct effect by periodontal pathological bacteria  or through an indirect effect caused by proinflammatory cytokines; this contribution could have a role as a cofactor to induce or accelerate the progress of AD thanks to the most recent etiopathogenetic theories giving inflammatory mechanisms a key role for this pathology. Analyzing the characteristics of both pathologies, we focused on their common aspects: high prevalence, peak of incidence, inflammatory pathogenesis, etc.
The literature proposes the hypothesis that the bacterial load and the inflammatory reaction related to periodontitis can intensify the inflammation in the central nervous system, eventually favoring the onset of disease [7,85]. Even if no direct evidence associates periodontitis with Alzheimer’s disease, preliminary indirect evidence is provided by a few clinical and epidemiological studies available. Particularly, the Nun Study analysis proposed a small number of teeth to be associated with the presence of dementia in old age ; however, it was not able to establish if this association is completely casual or partially casual. Moreover, this study evaluated the role of the APOE4ε; its absence would predispose to Alzheimer’s disease, but the mechanism behind this was not explained.
The study performed using the third National Health and Nutrition Examination Survey (NHANES III) derived data has related the presence of high IgG levels against P. gingivalis to a greater possibility of memory and cognitive impairment . In fact, a statistically significant relationship between IgG, P. gingivalis and dementia has been found. From these studies, a correlation between periodontitis and neurodegenerative diseases can be deduced, but neither can definitely prove their possible association nor demonstrate a possible mechanism through which periodontitis can induce the onset or the evolution of neurodegenerative diseases .
However, if these hypotheses were validated by future studies, the relevance of such gain would have immediate and significative implications. Particularly, the prevention and treatment of periodontitis could reduce the patient’s risk profile towards the development of Alzheimer’s disease ; there will be evidence that peripheral infections would need greater attention. In conclusion, today’s evidence seems to propose a possible relationship between periodontitis and neurodegenerative diseases, especially Alzheimer’s disease .
Nevertheless, today there is no definitive evidence to consider periodontitis as a risk factor, so more research will have to be conducted on this topic. Future studies that correlate periodontitis and Alzheimer’s disease should mainly focus on the possibility of preventing the onset of periodontal disease, the loss of dental elements, the reduction of local inflammation, and the predisposing oral factors of AD. Furthermore, the role of periodontal bacteria in the etiopathogenesis of Alzheimer’s disease should be investigated.
Authored By: Mario Dioguardi, Vito Crincoli, Luigi Laino, Mario Alovisi, Diego Sovereto, Filiberto Mastrangelo, Lucio Lo Russo, and Lorenzo Lo Muzio