Коморбидность заболеваний пародонта и болезни Альцгеймера

Заболевания пародонта относятся к числу наиболее распространенных заболеваний человека. В начале XXI в. сформировалась концепция «пародонтальной медицины», рассматривающая взаимосвязи патологии пародонта с другими заболеваниями организма. Сегодня с патологией пародонта связано более 50 различных системных заболеваний. Болезнь Альцгеймера является наиболее распространенной формой первичных дегенеративных деменций позднего возраста. К 2050 г. в мире число случаев достигнет уровня 140 млн. Анатомическая близость полости рта и головного мозга предполагает наличие связи между заболеваниями пародонта и патологией ЦНС. Авторы провели поиск источников в информационной базе Pubmed, опубликованных до 19.10.2025, в которых рассматривалась взаимосвязь патологии пародонта и болезни Альцгеймера. Было найдено 630 публикаций. В настоящем исследовании авторы проанализировали 121 публикацию из 423 источников, опубликованных за последние 5 лет. Полученные в ходе анализа данные свидетельствуют о связи болезни Альцгеймера с заболеваниями пародонта, наличии эпидемиологических и генетических параллелей, патогенетических взаимосвязях, подтвержденных клиническими и экспериментальными исследованиями. Porphyromonas gingivalis, посредством множества факторов вирулентности, выступает в качестве ключевого патогена при болезни Альцгеймера и пародонтите. Выполненный анализ исследований, проведенных учеными за последние 5 лет, позволяет сделать вывод о важности междисциплинарных подходов в понимании системных последствий заболеваний пародонта и их потенциального влияния на здоровье мозга. Взаимосвязь заболеваний пародонта и болезни Альцгеймера позволяет рассматривать здоровье полости рта как важный фактор в профилактике и в лечении болезни Альцгеймера.

1. Kassebaum NJ, Smith AGC, Bernabé E, Fleming TD, Reynolds AE, Vos T et al. Global, regional, and national prevalence, incidence, and disabilityadjusted life years for oral conditions for 195 countries, 1990–2015: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res. 2017;96(4):380–387. https://doi.org/10.1177/0022034517693566.

2. Balta MG, Papathanasiou E, Blix IJ, Van Dyke TE. Host Modulation and Treatment of Periodontal Disease. J Dent Res. 2021;100(8):798–809. https://doi.org/10.1177/0022034521995157.

3. O’Dwyer MC, Furgal A, Furst W, Ramakrishnan M, Capizzano N, Sen A, Klinkman M. The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011–2014. J Am Board Fam Med. 2023;36(2):313–324. https://doi.org/10.3122/jabfm.2022.220207R1.

4. Янешевич ОО, Кузьмина ЭМ, Максимовский ЮМ, Малый АЮ, Дмитриева ЛА, Ревазова ЗЭ и др. Клинические рекомендации (протоколы лечения) при диагнозе «Пародонтит». Режим доступа: https://minzdrav.gov-murman.ru/documents/poryadki-okazaniyameditsinskoy-pomoshchi/8_parodontit.pdf.

5. Williams RC, Offenbacher S. Periodontal medicine: The emergence of a new branch of periodontology. Periodontology 2000. 2000;23:9–12. https://doi.org/10.1034/j.1600-0757.2000.2230101.x.

6. Pai SI, Matheus HR, Guastaldi FPS. Effects of periodontitis on cancer outcomes in the era of immunotherapy. Lancet Healthy Longev. 2023;4(4):e166–e175. https://doi.org/10.1016/S2666-7568(23)00021-1.

7. Han J, Liu Y, Guo X, Gao G, Wu Q. Research Trends in the Comorbidity Between Periodontitis and Neurodegenerative Diseases. Int Dent J. 2025;75(2):564–574. https://doi.org/10.1016/j.identj.2024.07.1212.

8. Melo A, Flores-Fraile J, Lo Giudice R, Marchetti E, Nart J, Greethurst AR et al. Association Between Alzheimer’s Disease and Periodontal Inflammatory Parameters: A Systematic Review. J Clin Exp Dent. 2025;17(3):e310–e323. https://doi.org/10.4317/jced.62519.

9. Gharaibeh S, Alsabbah A, Alloubani A, Gharaibeh A. Reciprocal Interactions Between Periodontal Disease and Alzheimer’s Disease: Implications for Mutual Triggering, Exacerbation, and Treatment Interventions – A Comprehensive Review of the Literature. Neurol Int. 2025;17(6):81. https://doi.org/10.3390/neurolint17060081.

10. Трухан ДИ, Сулимов АФ. Коморбидность заболеваний пародонта и болезни Паркинсона. Acta Medica Eurasica. 2025;(2):95–104. https://doi.org/10.47026/2413-4864-2025-2-95-104.

11. Khan S, Barve KH, Kumar MS. Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer’s disease. Curr Neuropharmacol. 2020;18(10):1106–1125. https://doi.org/10.2174/1570159X18666200528142429.

12. Chen CK, Wu YT, Chang YC. Association between chronic periodontitis and the risk of Alzheimer’s disease: a retrospective, population-based, matched-cohort study. Alzheimers Res Ther. 2017;9(1):56. https://doi.org/10.1186/s13195-017-0282-6.

13. Choi S, Kim K, Chang J, Kim SM, Kim SJ, Cho HJ, Park SM. Association of Chronic Periodontitis on Alzheimer’s Disease or Vascular Dementia. J Am Geriatr Soc. 2019;67(6):1234–1239. https://doi.org/10.1111/jgs.15828.

14. Yoo JE, Huh Y, Park SH, Han K, Park HS, Cho KH et al. Association between Dental Diseases and Oral Hygiene Care and the Risk of Dementia: A Retrospective Cohort Study. J Am Med Dir Assoc. 2023;24(12):1924–1930. https://doi.org/10.1016/j.jamda.2023.08.011.

15. Bouziane A, Lattaf S, Abdallaoui Maan L. Effect of Periodontal Disease on Alzheimer’s Disease: A Systematic Review. Cureus. 2023;15(10):e46311. https://doi.org/10.7759/cureus.46311.

16. Leira Y, Domínguez C, Seoane J, Seoane-Romero J, Pías-Peleteiro JM, Takkouche B et al. Is Periodontal Disease Associated with Alzheimer’s Disease? A Systematic Review with Meta-Analysis. Neuroepidemiology. 2017;48(1-2):21–31. https://doi.org/10.1159/000458411.

17. Qiu C, Zhou W, Shi WT, Song ZC. Association between periodontitis and Alzheimer disease: a meta analysis. Shanghai Journal of Stomatology. 2020;29(6):661–668. (In Chinese) Available at: https://pubmed.ncbi.nlm.nih.gov/33778838.

18. Dhingra K, Grimm WD, Chaudhari PK, Verma F. Does periodontal disease elevate the risk of Alzheimer’s disease and mild cognitive impairment? Evid Based Dent. 2021;22(4):123–125. https://doi.org/10.1038/s41432-021-0214-y.

19. Hu X, Zhang J, Qiu Y, Liu Z. Periodontal disease and the risk of Alzheimer’s disease and mild cognitive impairment: a systematic review and metaanalysis. Psychogeriatrics. 2021;21(5):813–825. https://doi.org/10.1111/psyg.12743.

20. Kaliamoorthy S, Nagarajan M, Sethuraman V, Jayavel K, Lakshmanan V, Palla S. Association of Alzheimer’s disease and periodontitis – a systematic review and meta-analysis of evidence from observational studies. Med Pharm Rep. 2022;95(2):144–151. https://doi.org/10.15386/mpr-2278.

21. Liu S, Dashper SG, Zhao R. Association Between Oral Bacteria and Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2023;91(1):129–150. https://doi.org/10.3233/JAD-220627.

22. Marruganti C, Baima G, Aimetti M, Grandini S, Sanz M, Romandini M. Periodontitis and low cognitive performance: A population-based study. J Clin Periodontol. 2023;50(4):418–429. https://doi.org/10.1111/jcpe.13779.

23. Dibello V, Custodero C, Cavalcanti R, Lafornara D, Dibello A, Lozupone M et al. Impact of periodontal disease on cognitive disorders, dementia, and depression: a systematic review and meta-analysis. Geroscience. 2024;46(5):5133–5169. https://doi.org/10.1007/s11357-024-01243-8.

24. Arbildo-Vega HI, Cruzado-Oliva FH, Coronel-Zubiate FT, Aguirre-Ipenza R, Meza-Málaga JM, Luján-Valencia SA et al. Association between periodontal disease and Alzheimer’s disease: umbrella review. Front Dent Med. 2025;6:1635200. https://doi.org/10.3389/fdmed.2025.1635200.

25. Plachokova AS, Gjaltema J, Hagens ERC, Hashemi Z, Knüppe TBA, Kootstra TJM et al. Int J Mol Sci. 2024;25(8):4504. https://doi.org/10.3390/ijms25084504.

26. Rostagno AA. Pathogenesis of Alzheimer’s Disease. Int J Mol Sci. 2022;24(1):107. https://doi.org/10.3390/ijms24010107.

27. Twarowski B, Herbet M. Inflammatory Processes in Alzheimer’s Disease-Pathomechanism, Diagnosis and Treatment: A Review. Int J Mol Sci. 2023;24(7):6518. https://doi.org/10.3390/ijms24076518.

28. Pisani F, Pisani V, Arcangeli F, Harding A, Singhrao SK. The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology. Int J Environ Res Public Health. 2022;19(15):9386. https://doi.org/10.3390/ijerph19159386.

29. Silvestre FJ, Lauritano D, Carinci F, Silvestre-Rangil J, Martinez-Herrera M, Del Olmo A. Neuroinflammation, Alzheimer’s disease and periodontal disease: is there an association between the two processes? J Biol Regul Homeost Agents. 2017;31(2):189–196. Available at: https://pubmed.ncbi.nlm.nih.gov/28691472.

30. Huang Z, Hao M, Shi N, Wang X, Yuan L, Wang X. Porphyromonas gingivalis: a potential trigger of neurodegenerative disease. Front Immunol. 2025;16:1482033. https://doi.org/10.3389/fimmu.2025.1482033.

31. Abbayya K, Puthanakar NY, Naduwinmani S, Chidambar YS. Association between Periodontitis and Alzheimer’s Disease. N Am J Med Sci. 2015;7(6):241–246. https://doi.org/10.4103/1947-2714.159325.

32. Kong LWY, He XT, Chen FM, Li X. Influence of periodontal microbial homeostasis on neurodegenerative diseases and its therapeutic perspectives. Chinese Journal of Stomatology. 2024;59(8):851–857. (In Chinese) https://doi.org/10.3760/cma.j.cn112144-20231027-00225.

33. Pruntel SM, van Munster BC, de Vries JJ, Vissink A, Visser A. Oral Health as a Risk Factor for Alzheimer Disease. J Prev Alzheimers Dis. 2024;11(1):249–258. https://doi.org/10.14283/jpad.2023.82.

34. Villar A, Paladini S, Cossatis J. Periodontal Disease and Alzheimer’s: Insights from a Systematic Literature Network Analysis. J Prev Alzheimers Dis. 2024;11(4):1148–1165. https://doi.org/10.14283/jpad.2024.79.

35. Chalmers JC, Hernandez-Kapila YL. The role of the oral microbiome, host response, and periodontal disease treatment in Alzheimer’s disease: A primer. Periodontol 2000. 2025;98(1):220–227. https://doi.org/10.1111/prd.12631.

36. Parra-Torres V, Melgar-Rodríguez S, Muñoz-Manríquez C, Sanhueza B, Cafferata EA, Paula-Lima AC, Díaz-Zúñiga J. Periodontal bacteria in the brain-Implication for Alzheimer’s disease: A systematic review. Oral Dis. 2023;29(1):21–28. https://doi.org/10.1111/odi.14054.

37. Qian XS, Ge S. The state of the art research findings on the relationship between chronic periodontitis and Alzheimer’s disease: a review. Chinese Journal of Stomatology. 2018;53(4):275–279. (In Chinese) https://doi.org/10.3760/cma.j.issn.1002-0098.2018.04.012.

38. Li X, Kiprowska M, Kansara T, Kansara P, Li P. Neuroinflammation: A Distal Consequence of Periodontitis. J Dent Res. 2022;101(12):1441–1449. https://doi.org/10.1177/00220345221102084.

39. Sureda A, Daglia M, Argüelles Castilla S, Sanadgol N, Fazel Nabavi S, Khan H et al. Oral microbiota and Alzheimer’s disease: Do all roads lead to Rome? Pharmacol Res. 2020;151:104582. https://doi.org/10.1016/j.phrs.2019.104582.

40. Martínez-Martínez V, Rodríguez-Lozano FJ, Pecci-Lloret MP, Pérez-Guzmán N. Association Between Oral Dysbiosis and Alzheimer’s Disease: A Systematic Review. J Clin Med. 2025;14(10):3415. https://doi.org/10.3390/jcm14103415.

41. Eslami S, Hosseinzadeh Shakib N, Fooladfar Z, Nasrollahian S, Baghaei S, Mosaddad SA, Motamedifar M. The role of periodontitis-associated bacteria in Alzheimer’s disease: A narrative review. J Basic Microbiol. 2023;63(10):1059–1072. https://doi.org/10.1002/jobm.202300250.

42. Lamphere AK, Nieto VK, Kiser JR, Haddlesey CB. Potential mechanisms between periodontitis and Alzheimer’s disease: a scoping review. Can J Dent Hyg. 2023;57(1):52–60. Available at: https://pubmed.ncbi.nlm.nih.gov/36968797.

43. Klonaris N, Murcia JDG, Patil S, Freitas CMT. The Role of Periodontitis in Increasing Cognitive Decline in Alzheimer’s Disease. J Contemp Dent Pract. 2025;26(3):311–320. https://doi.org/10.5005/jp-journals-10024-3847.

44. Sansores-España D, Carrillo-Avila A, Melgar-Rodriguez S, Díaz-Zuñiga J, Martínez-Aguilar V. Periodontitis and Alzheimer´s disease. Med Oral Patol Oral Cir Bucal. 2021;26(1):e43–e48. https://doi.org/10.4317/medoral.23940.

45. Gaur S, Agnihotri R. Alzheimer’s disease and chronic periodontitis: is there an association? Geriatr Gerontol Int. 2015;15(4):391–404. https://doi.org/10.1111/ggi.12425.

46. Liccardo D, Marzano F, Carraturo F, Guida M, Femminella GD, Bencivenga L et al. Potential Bidirectional Relationship Between Periodontitis and Alzheimer’s Disease. Front Physiol. 2020;11:683. https://doi.org/10.3389/fphys.2020.00683.

47. Mao S, Huang CP, Lan H, Lau HG, Chiang CP, Chen YW. Association of periodontitis and oral microbiomes with Alzheimer’s disease: A narrative systematic review. J Dent Sci. 2022;17(4):1762–1779. https://doi.org/10.1016/j.jds.2022.07.001.

48. Wang RP, Huang J, Chan KWY, Leung WK, Goto T, Ho YS, Chang RC. IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease. J Neuroinflammation. 2023;20(1):71. https://doi.org/10.1186/s12974-023-02747-4.

49. Li R, Wang J, Xiong W, Luo Y, Feng H, Zhou H et al. The oral-brain axis: can periodontal pathogens trigger the onset and progression of Alzheimer’s disease? Front Microbiol. 2024;15:1358179. https://doi.org/10.3389/fmicb.2024.1358179.

50. Salhi L, Al Taep Y, Salmon E, Van Hede D, Lambert F. How Periodontitis or Periodontal Bacteria Can Influence Alzheimer’s Disease Features? A Systematic Review of Pre-Clinical Studies. J Alzheimers Dis. 2023;96(3):979–1010. https://doi.org/10.3233/JAD-230478.

51. Lu J, Zhang S, Huang Y, Qian J, Tan B, Qian X et al. Periodontitis-related salivary microbiota aggravates Alzheimer’s disease via gut-brain axis crosstalk. Gut Microbes. 2022;14(1):2126272. https://doi.org/10.1080/19490976.2022.2126272.

52. Malcangi G, Marinelli G, Inchingolo AD, Trilli I, Ferrante L, Casamassima L et al. Salivaomics: New Frontiers in Studying the Relationship Between Periodontal Disease and Alzheimer’s Disease. Metabolites. 2025;15(6):389. https://doi.org/10.3390/metabo15060389.

53. Singhrao SK, Harding A, Poole S, Kesavalu L, Crean S. Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer’s Disease. Mediators Inflamm. 2015;2015:137357. https://doi.org/10.1155/2015/137357.

54. Yadalam PK, Chatterjee S, Natarajan PM, Ardila CM. Comparison of light gradient boosting and logistic regression for interactomic hub genes in Porphyromonas gingivalis and Fusobacterium nucleatum-induced periodontitis with Alzheimer’s disease. Front Oral Health. 2025;6:1463458. https://doi.org/10.3389/froh.2025.1463458.

55. Pisani F, Pisani V, Arcangeli F, Harding A, Singhrao SK. Treponema denticola Has the Potential to Cause Neurodegeneration in the Midbrain via the Periodontal Route of Infection-Narrative Review. Int J Environ Res Public Health. 2023;20(11):6049. https://doi.org/10.3390/ijerph20116049.

56. Cichońska D, Mazuś M, Kusiak A. Recent Aspects of Periodontitis and Alzheimer’s Disease-A Narrative Review. Int J Mol Sci. 2024;25(5):2612. https://doi.org/10.3390/ijms25052612.

57. Olsen I. Can Porphyromonas gingivalis Contribute to Alzheimer’s Disease Already at the Stage of Gingivitis? J Alzheimers Dis Rep. 2021;5(1):237–241. https://doi.org/10.3233/ADR-210006.

58. Wu H, Qiu W, Zhu X, Li X, Xie Z, Carreras I et al. The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways. Front Aging Neurosci. 2022;14:912709. https://doi.org/10.3389/fnagi.2022.912709.

59. El Choueiri E, El Choueiri J, El Choueiri A. Oral health as a modifiable risk factor for neurodegeneration: Prudent optimism and interdisciplinary action. J Clin Neurosci. 2025;138:111354. https://doi.org/10.1016/j.jocn.2025.111354.

60. Dong C, Xue F, Ji X, Zhang D. Analysis and Research on the Relationship between Oral Microorganisms and Alzheimer’s Disease. Altern Ther Health Med. 2024:AT10254. Available at: https://pubmed.ncbi.nlm.nih.gov/39038355.

61. Bostanci N, Belibasakis GN. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett. 2012;333(1):1–9. https://doi.org/10.1111/j.1574-6968.2012.02579.x.

62. Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012;10(10):717–725. https://doi.org/10.1038/nrmicro2873.

63. Costa MJF, de Araújo IDT, da Rocha Alves L, da Silva RL, Dos Santos Calderon P, Borges BCD et al. Relationship of Porphyromonas gingivalis and Alzheimer’s disease: a systematic review of pre-clinical studies. Clin Oral Investig. 2021;25(3):797–806. https://doi.org/10.1007/s00784-020-03764-w.

64. Said-Sadier N, Sayegh B, Farah R, Abbas LA, Dweik R, Tang N et al. Association between Periodontal Disease and Cognitive Impairment in Adults. Int J Environ Res Public Health. 2023;20(6):4707. https://doi.org/10.3390/ijerph20064707.

65. Sadiqa A, Khan MK. Mediators of Periodontitis complementing the development of Neural Disorders. Pak J Med Sci. 2024;40(1):214–221. https://doi.org/10.12669/pjms.40.1.8097.

66. Singhrao SK, Olsen I. Assessing the role of Porphyromonas gingivalis in periodontitis to determine a causative relationship with Alzheimer’s disease. J Oral Microbiol. 2019;11(1):1563405. https://doi.org/10.1080/20002297.2018.1563405.

67. Kanagasingam S, Chukkapalli SS, Welbury R, Singhrao SK. Porphyromonas gingivalis is a Strong Risk Factor for Alzheimer’s Disease. J Alzheimers Dis Rep. 2020;4(1):501–511. https://doi.org/10.3233/ADR-200250.

68. Elwishahy A, Antia K, Bhusari S, Ilechukwu NC, Horstick O, Winkler V. Porphyromonas Gingivalis as a Risk Factor to Alzheimer’s Disease: A Systematic Review. J Alzheimers Dis Rep. 2021;5(1):721–732. https://doi.org/10.3233/ADR-200237.

69. Olsen I. Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer’s Disease. Front Neurosci. 2021;15:691016. https://doi.org/10.3389/fnins.2021.691016.

70. Seyedmoalemi MA, Saied-Moallemi Z. Association between periodontitis and Alzheimer’s disease: A narrative review. IBRO Neurosci Rep. 2025;18:360–365. https://doi.org/10.1016/j.ibneur.2024.12.004.

71. Owoyele PV, Malekzadeh S. Porphyromonas gingivalis, neuroinflammation and Alzheimer’s disease. Niger J Physiol Sci. 2022;37(2):157–164. https://doi.org/10.54548/njps.v37i2.1.

72. Sarmiento-Ordóñez JM, Brito-Samaniego DR, Vásquez-Palacios AC, Pacheco-Quito EM. Association Between Porphyromonas gingivalis and Alzheimer’s Disease: A Comprehensive Review. Infect Drug Resist. 2025;18:2119–2136. https://doi.org/10.2147/IDR.S491628.

73. Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333. https://doi.org/10.1126/sciadv.aau3333.

74. Rozenblum G, Ait-Aissa K, Zahran G, Alipour M, Sahyoun AM, Munkhsaikhan U et al. Unraveling the oral microbiome's role in Alzheimer's disease: From pathophysiology to therapeutic potential. Alzheimers Dement. 2025;21(12):e71011. https://doi.org/10.1002/alz.71011.

75. Cichońska D, Mazuś M, Kusiak A. Recent Aspects of Periodontitis and Alzheimer’s Disease-A Narrative Review. Int J Mol Sci. 2024;25(5):2612. https://doi.org/10.3390/ijms25052612.

76. Kouki MA, Pritchard AB, Alder JE, Crean S. Do Periodontal Pathogens or Associated Virulence Factors Have a Deleterious Effect on the Blood-Brain Barrier, Contributing to Alzheimer’s Disease? J Alzheimers Dis. 2022;85(3):957–973. https://doi.org/10.3233/JAD-215103.

77. Loughman A, Adler CJ, Macpherson H. Unlocking Modifiable Risk Factors for Alzheimer’s Disease: Does the Oral Microbiome Hold Some of the Keys? J Alzheimers Dis. 2023;92(4):1111–1129. https://doi.org/10.3233/JAD-220760.

78. Harding A, Kanagasingam S, Welbury R, Singhrao SK. Periodontitis as a Risk Factor for Alzheimer’s Disease: The Experimental Journey So Far, with Hope of Therapy. Adv Exp Med Biol. 2022;1373:241–260. https://doi.org/10.1007/978-3-030-96881-6_13.

79. Fu Y, Xu X, Zhang Y, Yue P, Fan Y, Liu M et al. Oral Porphyromonas gingivalis Infections Increase the Risk of Alzheimer’s Disease: A Review. Oral Health Prev Dent. 2023;21:7–16. https://doi.org/10.3290/j.ohpd.b3818045.

80. Harding A, Robinson S, Crean S, Singhrao SK. Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer’s Disease? J Alzheimers Dis. 2017;58(2):337–348. https://doi.org/10.3233/JAD-170046.

81. Jungbauer G, Stähli A, Zhu X, Auber Alberi L, Sculean A, Eick S. Periodontal microorganisms and Alzheimer disease – A causative relationship? Periodontol 2000. 2022;89(1):59–82. https://doi.org/10.1111/prd.12429.

82. Liu S, Butler CA, Ayton S, Reynolds EC, Dashper SG. Porphyromonas gingivalis and the pathogenesis of Alzheimer’s disease. Crit Rev Microbiol. 2024;50(2):127–137. https://doi.org/10.1080/1040841X.2022.2163613.

83. Ma X, Shin YJ, Yoo JW, Park HS, Kim DH. Extracellular vesicles derived from Porphyromonas gingivalis induce trigeminal nerve-mediated cognitive impairment. J Adv Res. 2023;54:293–303. https://doi.org/10.1016/j.jare.2023.02.006.

84. Shawkatova I, Durmanova V, Javor J. Alzheimer’s Disease and Porphyromonas gingivalis: Exploring the Links. Life. 2025;15(1):96. https://doi.org/10.3390/life15010096.

85. Polishchuk H, Synowiec A, Zubrzycka N, Kantyka T. Porphyromonas gingivalis: Multiple Tools of an Inflammatory Damage. Mol Oral Microbiol. 2025;40(5):159–176. https://doi.org/10.1111/omi.12496.

86. Nie R, Wu Z, Ni J, Zeng F, Yu W, Zhang Y et al. Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages. J Alzheimers Dis. 2019;72(2):479–494. https://doi.org/10.3233/JAD-190298.

87. Singhrao SK. Porphyromonas gingivalis-lipopolysaccharide and amyloid-β: A dangerous liaison for impairing memory? J Alzheimers Dis. 2025;106(2):537–539. https://doi.org/10.1177/13872877251343317.

88. Verma A, Azhar G, Patyal P, Zhang X, Wei JY. Porphyromonas gingivalis-Lipopolysaccharide Induced Caspase-4 Dependent Noncanonical Inflammasome Activation Drives Alzheimer’s Disease Pathologies. Cells. 2025;14(11):804. https://doi.org/10.3390/cells14110804.

89. Kong L, Li J, Gao L, Zhao Y, Chen W, Wang X et al. Periodontitis-induced neuroinflammation triggers IFITM3-Aβ axis to cause alzheimer’s diseaselike pathology and cognitive decline. Alzheimers Res Ther. 2025;17(1):166. https://doi.org/10.1186/s13195-025-01818-3.

90. Arévalo-Caro C, Arce Retana M, Losada Amaya S, Arboleda H, Gallart-Palau X, Serra A. APOE4, Alzheimer’s and periodontal disease: A scoping review. Ageing Res Rev. 2025;105:102649. https://doi.org/10.1016/j.arr.2024.102649.

91. Olsen I, Singhrao SK. Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease. J Oral Microbiol. 2020;12(1):1820834. https://doi.org/10.1080/20002297.2020.1820834.

92. Mo D, Li X, He J, Lin X, Wang P, Zeng Y et al. Chronic gingivitis increases the risk of early-onset Alzheimer’s disease. J Alzheimers Dis. 2025;105(4):1321–1340. https://doi.org/10.1177/13872877251336259.

93. Yang K, Zhang Z, Zhang Q, Zhang H, Liu X, Jia Z et al. Potential diagnostic markers and therapeutic targets for periodontitis and Alzheimer’s disease based on bioinformatics analysis. J Periodontal Res. 2024;59(2):366–380. https://doi.org/10.1111/jre.13220.

94. Jin J, Guang M, Li S, Liu Y, Zhang L, Zhang B et al. Immune-related signature of periodontitis and Alzheimer’s disease linkage. Front Genet. 2023;14:1230245. https://doi.org/10.3389/fgene.2023.1230245.

95. Jin J, Guang M, Ogbuehi AC, Li S, Zhang K, Ma Y et al. Shared Molecular Mechanisms between Alzheimer’s Disease and Periodontitis Revealed by Transcriptomic Analysis. Biomed Res Int. 2021;2021:6633563. https://doi.org/10.1155/2021/6633563.

96. Ge F, Zhao Y, Zheng J, Xiang Q, Luo P, Zhu L, He H. Discovering common pathogenetic processes between periodontitis and Alzheimer’s disease by bioinformatics and system biology approach. BMC Oral Health. 2024;24(1):1074. https://doi.org/10.1186/s12903-024-04775-9.

97. Olsen I, Singhrao SK. Is there a link between genetic defects in the complement cascade and Porphyromonas gingivalis in Alzheimer’s disease? J Oral Microbiol. 2019;12(1):1676486. https://doi.org/10.1080/20002297.2019.1676486.

98. Carter CJ, France J, Crean S, Singhrao SK. The Porphyromonas gingivalis/ Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer’s Disease, Diabetes and Cardiovascular Diseases. Front Aging Neurosci. 2017;9:408. https://doi.org/10.3389/fnagi.2017.00408.

99. Magnusson A, Wu R, Demirel I. Porphyromonas gingivalis triggers microglia activation and neurodegenerative processes through NOX4. Front Cell Infect Microbiol. 2024;14:1451683. https://doi.org/10.3389/fcimb.2024.1451683.

100. Zhu H, Huang C, Luo Z, Wu L, Cheng X, Wu H. Porphyromonas gingivalis Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer’s Disease. J Dent Res. 2025;104(4):439–448. https://doi.org/10.1177/00220345241303141.

101. Goyal L, Gupta S, Perambudhuru Y. Association between periodontitis and cognitive impairment in adults. Evid Based Dent. 2023;24(3):123–124. https://doi.org/10.1038/s41432-023-00915-2.

102. Merchant AT, Yi F, Vidanapathirana NP, Lohman M, Zhang J, Newman-Norlund RD, Fridriksson J. Antibodies against Periodontal Microorganisms and Cognition in Older Adults. JDR Clin Trans Res. 2023;8(2):148–157. https://doi.org/10.1177/23800844211072784.

103. Arévalo-Caro C, López D, Sánchez Milán JA, Lorca C, Mulet M, Arboleda H et al. Periodontal Indices as Predictors of Cognitive Decline: Insights from the PerioMind Colombia Cohort. Biomedicines. 2025;13(1):205. https://doi.org/10.3390/biomedicines13010205.

104. Ide M, Harris M, Stevens A, Sussams R, Hopkins V, Culliford D et al. Periodontitis and Cognitive Decline in Alzheimer’s Disease. PLoS ONE. 2016;11(3):e0151081. https://doi.org/10.1371/journal.pone.0151081.

105. Leblhuber F, Huemer J, Steiner K, Gostner JM, Fuchs D. Knock-on effect of periodontitis to the pathogenesis of Alzheimer’s disease? Wien Klin Wochenschr. 2020;132(17-18):493–498. https://doi.org/10.1007/s00508-020-01638-5.

106. Carballo Á, López-Dequidt I, Custodia A, Botelho J, Aramburu-Núñez M, Machado V et al. Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer’s disease to this relationship. J Clin Periodontol. 2023;50(11):1444–1454. https://doi.org/10.1111/jcpe.13861.

107. Barbarisi A, Visconti V, Lauritano D, Cremonini F, Caccianiga G, Ceraulo S. Correlation between Periodontitis and Onset of Alzheimer’s Disease: A Literature Review. Dent J. 2024;12(10):331. https://doi.org/10.3390/dj12100331.

108. Guo H, Chang S, Pi X, Hua F, Jiang H, Liu C et al.The Effect of Periodontitis on Dementia and Cognitive Impairment: A Meta-Analysis. Int J Environ Res Public Health. 2021;18(13):6823. https://doi.org/10.3390/ijerph18136823.

109. Fu YD, Li CL, Hu CL, Pei MD, Cai WY, Li YQ et al. Meta Analysis of the Correlation between Periodontal Health and Cognitive Impairment in the Older Population. J Prev Alzheimers Dis. 2024;11(5):1307–1315. https://doi.org/10.14283/jpad.2024.87.

110. Borsa L, Dubois M, Sacco G, Lupi L. Analysis the Link between Periodontal Diseases and Alzheimer’s Disease: A Systematic Review. Int J Environ Res Public Health. 2021;18(17):9312. https://doi.org/10.3390/ijerph18179312.

111. Olsen I, Taubman MA, Singhrao SK. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease. J Oral Microbiol. 2016;8:33029. https://doi.org/10.3402/jom.v8.33029.

112. Pritchard AB, Crean S, Olsen I, Singhrao SK. Periodontitis, Microbiomes and their Role in Alzheimer’s Disease. Front Aging Neurosci. 2017;9:336. https://doi.org/10.3389/fnagi.2017.00336.

113. Cesari C, Belleri G, Fabrizi S, Zangari F. Linking periodontitis and Alzheimer’s disease: systemic inflammation as a shared mechanism. Acad Mol Biol Genom. 2025;(2):2. https://doi.org/10.20935/AcadMolBioGen7734.

114. Dioguardi M, Crincoli V, Laino L, Alovisi M, Sovereto D, Mastrangelo F et al. The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review. J Clin Med. 2020;9(2):495. https://doi.org/10.3390/jcm9020495.

115. Zou Q, Xie H, Yang W, Xu J, Ying S, Liao X et al. Advances in the study of the relationship between Porphyromonas gingivalis and various diseases. Front Cell Dev Biol. 2025;13:1480233. https://doi.org/10.3389/fcell.2025.1480233.

116. Murray PE, Coffman JA, Garcia-Godoy F. Oral Pathogens’ Substantial Burden on Cancer, Cardiovascular Diseases, Alzheimer’s, Diabetes, and Other Systemic Diseases: A Public Health Crisis-A Comprehensive Review. Pathogens. 2024;13(12):1084. https://doi.org/10.3390/pathogens13121084.

117. Werber T, Bata Z, Vaszine ES, Berente DB, Kamondi A, Horvath AA. The Association of Periodontitis and Alzheimer’s Disease: How to Hit Two Birds with One Stone. J Alzheimers Dis. 2021;84(1):1–21. https://doi.org/10.3233/JAD-210491.

118. Bai XB, Zhou LJ, Lin WZ, Zhu YQ. Research progress in association of neurological disorders and periodontal diseases. Chinese Journal of Stomatology. 2022;57(5):529–534. (In Chinese) https://doi.org/10.3760/cma.j.cn112144-20220312-00103.

119. Qi X, Zhu Z, Wang K, Zheng Y, Li A, Wu B. Association of Gum Treatment with Cognitive Decline and Dementia Risk among Older Adults with Periodontal Symptoms: A 12-Year Prospective Cohort Study. Neuroepidemiology. 2025;59(4):313–322. https://doi.org/10.1159/000540086.

120. 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. https://doi.org/10.2147/JIR.S255309.

121. Ryder MI, Xenoudi P. Alzheimer disease and the periodontal patient: New insights, connections, and therapies. Periodontol 2000. 2021;87(1):32–42. https://doi.org/10.1111/prd.12389.

122. Ryder MI. Porphyromonas gingivalis and Alzheimer disease: Recent findings and potential therapies. J Periodontol. 2020;91(S1):S45–S49. https://doi.org/10.1002/JPER.20-0104.

123. Dibello V, Lozupone M, Manfredini D, Dibello A, Zupo R, Sardone R et al. Oral frailty and neurodegeneration in Alzheimer’s disease. Neural Regen Res. 2021;16(11):2149–2153. https://doi.org/10.4103/1673-5374.310672.

124. Olsen I. Porphyromonas Gingivalis May Seek the Alzheimer’s Disease Brain to Acquire Iron from Its Surplus. J Alzheimers Dis Rep. 2021;5(1):79–86. https://doi.org/10.3233/ADR-200272.