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International Journal of Medical and Biomedical Studies (IJMBS) || ISSN(online): 2589-8698 || ISSN(print): 2589-868X || International Journal of Medical and Biomedical Studies Available Online at www.ijmbs.info PubMed (National Library of Medicine ID: 101738825) Index Copernicus Value 2018: 75.71 Review Article Volume 4, Issue 2; February: 2020; Page No. 274-278 RELATIONSHIP BETWEEN ALZHEIMER’S DISEASE & PERIODONTITIS -A LITERATURE REVIEW Nivetha K1, Ayswarya V Vummidi2, Paavai Ilango3*, Abirami T4, Arulpari Mahalingam5, Vineela Katam Reddy6, Angel Infant R7, Meenambal A8 1Intern, Department of Periodontology, Priyadarshini Dental College and Hospital, Thiruvallur, Tamil Nadu, India 2MDS, Senior lecturer, Department of Periodontology, Priyadarshini Dental College and Hospital, Thiruvallur, Tamil Nadu, India 3*MDS, Professor and Head, Department of Periodontology, Priyadarshini Dental College and Hospital, Thiruvallur, Tamil Nadu, India 4MDS, Senior lecturer, Department of Periodontology, Priyadarshini Dental College and Hospital, Thiruvallur, Tamil Nadu, India 5MDS, Professor, Department of Pedodontics, Thai Moogambigai Dental College and Hospital, Chennai, Tamil Nadu, India 6MDS, Professor, Department of Periodontology, Indira Gandhi Institute of Dental Sciences, Pondicherry, Tamil Nadu, India 7BDS, Tutor, Department of Periodontology, Priyadarshini Dental College and Hospital, Thiruvallur, Tamil Nadu, India 8BDS, Tutor, Department of periodontology, Priyadarshini Dental College and Hospital, Thiruvallur, Tamil Nadu, India Article Info: Received 07 February 2020; Accepted 27 February 2020 DOI: https://doi.org/10.32553/ijmbs.v4i2.999 Corresponding author: Dr. Paavai Ilango Conflict of interest: No conflict of interest. Abstract Periodontitis is the microbial infection often causing inflammation of the gingiva, bone loss and tooth mobility. Apart from periodontitis, periodontal bacteria like Porphyromonas gingivalis, Spirochetes, Treponema denticola are known to cause systemic diseases such as cardiovascular diseases, preterm low birth weight infants, Alzheimer’s diseases etc. Alzheimer’s disease is a progressive mental deterioration of the brain that can occur in middle or old aged individual due to generalized regeneration of neurons in the brain. Literature has shown that inflammation plays a vital role in the progression of Alzheimer’s disease where periodontitis is a risk factor proving the focal infection theory. This article reviews the relationship of periodontitis in Alzheimer’s disease and its role in modifying the disease. Keywords: Alzheimer’s Disease, Chronic Periodontitis, Periomedicine, Inflammation two-way relationship exists between periodontal disease Introduction and systemic health or disease. Inflammation is known to be a protective response that Untreated periodontitis can alter various systemic focuses on the removal of stimuli responsible for damage diseases progression and one such is Alzheimer’s disease. to the tissues, thereby leading to restoration of health. Alzheimer’s disease is a progressive disease that Periodontitis is an inflammatory condition representing degenerates brain cell connection and the cells die the response of periodontal tissues to bacteria like eventually destroying memory and other mental Porphyromonas gingivalis, Treponema denticola and functions. Spirochetes. Periodontitis leads to inflammation of gingival and destruction of periodontal tissues. The Though periodontopathic bacteria are responsible for characteristics of periodontitis include microbial biofilm the occurrence of periodontal disease, the progression of formation, gingival inflammation, alveolar bone loss and disease mainly depends on host inflammatory response.3 attachment loss.1 In an healthy periodontium, a balance between bacteria and host response is well maintained, whereas in Periodontal medicine establishes a strong relation periodontitis, that balance is disrupted; as the between periodontal health or disease and systemic periodontal bacteria and their products enter the blood condition. Periodontitis as a source of inflammation stream from periodontal pockets, resulting in bacteremia contribute to exacerbate many systemic diseases like and dissemination of its products in systemic circulation, diabetes, cardiovascular diseases, respiratory diseases, following which innate and adaptive immune response pregnancy (PROM- Premature rupture of membrane), results in changes of local vasculature, generation of an neurological diseases etc. Hence, periodontitis is not inflammatory response and the secretion of pro- limited to destruction of periodontal tissues; but also inflammatory cytokines like Tumor necrosis factor- modify systemic diseases and vice versa.2 Thus, a proven α(TNF-α), Interleukin-1(IL-1) and Interleukin-6(IL-6).This 274 | P a g e Nivetha K et al. International Journal of Medical and Biomedical Studies (IJMBS) leads to the activation of osteoclasts, Matrix metallo Discussion proteins(MMP) and decreased collagen activity.4 Thus, Link between Alzheimer’s and periodontitis: the disease is exhibited with clinical signs of tissue and bone destruction. This immuno-inflammatory condition Inflammation seems to play a vital role in association is said to play a vital role in the onset and progression of between Alzheimer’s disease and Periodontitis. alzheimer’s disease, though its pathogenesis is not Periodontal disease through the production of cytokines completely understood. and angiogenic factors cause cognitive disorders.13There are various mechanism which brings a phenomenal Alzheimer’s disease is characterised by lack of memory, association between Alzheimer’s disease and feeling difficulty in thinking & understanding, confusion, periodontitis. These mechanisms involve bacteria and problems with language, disorientation, mood swings, their products, inflammatory mediators and vascular wandering or getting lost, not managing self-care, changes ultimately progressing to Alzheimer’s disease.14 aggression, depression, repetition of meaningless own words, inability to coordinate muscle movements, A. Based on microbial association: gradually leading to loss of body functions and death.5 Several researches have been conducted to establish the Plaque and neuro-fibrillary tangles in the brain are association of periodontitis causing Alzheimer's disease. considered as the reason for progression of the disease. Periodontal bacteria from periodontitis affect the Barry et al in 1980 classified the progression of function of brain by inflammatory molecules.15,16 Alzheimer’s disease into 7 stages. Normal, Normal aged Dominy et al on analyzing the brain tissue, spinal forgetfulness, mild cognitive impairment, mild fluid and saliva from Alzheimer’s disease patients found Alzheimer’s disease, moderate Alzheimer’s, moderately that Porphyromonas gingivalis, an important pathogen in severe Alzheimer’s disease, severe Alzheimer’s disease 6 the development of chronic periodontitis plays a and death. Though Alzheimer’s disease cannot be significant role in developing Amyloid β plaques, completely treated symptoms can be improved dementia and Alzheimer’s disease.17,18,19,20,21 Toxic temporarily by medications and relieving the risk factors. proteases from the bacterium called gingipains secreted The etiology of alzheimer’s disease is yet to be fully by Porphyromonas gingivalis are found in the brain understood. Many studies reveal that 70% of the samples of Alzheimer’s disease patients which mediates etiology is hereditary and other causes involved includes 7 the toxicity of pathogen in fibroblast, endothelial and head injuries and depression. epithelial cells.22,23,24 Dominy et al found COR388 as the The clinical sequence of alzheimer’s disease is initiated effective gingipain inhibitor in a mouse model as it was by dysfunction of autophagy.8 Autophagy is a lysosome able to reduce neuro inflammation in the brain by dependent, homeostatic process, in which organelles reducing the Porphyromonas gingivalis bacteria.25 and proteins are degraded and recycled into energy. It is Poole et al have reported that Porphyromonas specifically important in non-proliferative cells, like gingivalis lipopolysaccharide have been found in the neurons where its failure leads to neurodegenerative brains of Alzheimer’s disease patients, supporting the diseases. Physiologically as cells are aging, the hypothesis that Porphyromonas gingivalis play an unnecessary proteins or those produced in excess that important role in the pathogenesis of Alzheimer’s alter cellular balance are eliminated rapidly. The disease.26 Porphyromonas gingivalis can also enter the complete disintegration of unnecessary proteins like brain by infecting monocytes followed by brain Amyloid β protein(Aβ) which is necessary for cell viability recruitment.27 Porphyromonas gingivalis cross the blood are done by proteasomal digestion and autophagy. Thus, brain barrier and affect the brain activity by releasing Alzheimer’s disease is initiated from inflammation by Aβ- cytokines resulting in Alzheimer’sdisease.28 amyloid proteins, hyper-phosphorylated tau protein or Balin et al has reported that Chlamydia pneumoniae components of degenerated neurons. Evidently, was present in 19 post-mortem brain sample of microglial cells at low levels are neuro-protective in Alzheimer’s disease patients influencing the role of this 9 nature. When exposed to systemic inflammatory signals particular bacteria in the pathogenesis of Alzheimer’s or by aging, the microglial cells are activated which alter disease.29 the normal cell morphology by secreting
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