Poor Oral Health as a Chronic, Potentially Modifiable Dementia Risk Factor: Review of the Literature

Abstract

Poor oral health, including caries, tooth loss, and periodontitis, is ubiquitous worldwide, and is potentially treatable and preventable. Like adverse oral health conditions, Alzheimer disease and related disorders are also very common among aging populations. Established risk factors for Alzheimer disease include cerebrovascular disease and its vascular risk factors, many of which share associations with evidence of systemic inflammation also identified in periodontitis and other poor oral health states. In this review, we present epidemiologic evidence of links between poor oral health and both prevalent and incident cognitive impairment, and review plausible mechanisms linking these conditions, including evidence from compelling animal models. Considering that a large etiologic fraction of dementia remains unexplained, these studies argue for further multidisciplinary research between oral health conditions, including translational, epidemiologic, and possibly clinical treatment studies.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Paper of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Gurland BJ, Wilder DE, Lantigua R, et al. Rates of dementia in three ethnoracial groups. Int J Geriatr Psychiatry. 1999;14:481–93.

    PubMed  CAS  Google Scholar 

  2. 2.

    Mayeux R. Epidemiology of neurodegeneration. Annu Rev Neurosci. 2003;26:81–104.

    PubMed  CAS  Google Scholar 

  3. 3.

    Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60:1119–22.

    PubMed  Google Scholar 

  4. 4.

    Mayeux R, Apolipoprotein E. Alzheimer disease, and African Americans. Arch Neurol. 2003;60:161–3.

    PubMed  Google Scholar 

  5. 5.

    Tang MX, Stern Y, Marder K, et al. The APOE-e4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998;279:751–5.

    PubMed  CAS  Google Scholar 

  6. 6.

    • Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011;10:819–28. This review places into perspective the etiologic fraction of several lifestyle and vascular risk factors for AD and underscores the impact that identification and elimination of others factors, such as oral health, could have on disease prevalence.

    PubMed  Google Scholar 

  7. 7.

    Noble JM, Scarmeas N. Cognitive impairment. In: Lamster IB, Northridge ME, editors. Improving oral health for the elderly. New York: Springer Books; 2008.

    Google Scholar 

  8. 8.

    Miller AJ, Brunelle JA, Carlos JP, Brown LJ, Löe H. Oral health of United States adults. Bethesda: US Department of Health & Human Services, Public Health Service, National Institutes of Health; 1987.

    Google Scholar 

  9. 9.

    Beck JD, Koch GG, Rozier RG, Tudor GE. Prevalence and risk indicators for periodontal attachment loss in a population of older community-dwelling blacks and whites. J Periodontol. 1990;61:521–8.

    PubMed  CAS  Google Scholar 

  10. 10.

    Petersen PE. The world oral health report 2003: continuous improvement of oral health in the 21st century – the approach of the WHO Global Oral Health Programme. Community Dent Oral Epidemiol. 2003;31 Suppl 1:3–23.

    PubMed  Google Scholar 

  11. 11.

    Petersen PE, Yamamoto T. Improving the oral health of older people: the approach of the WHO Global Oral Health Programme. Community Dent Oral Epidemiol. 2005;33:81–92.

    PubMed  Google Scholar 

  12. 12.

    Machtei EE, Hausmann E, Dunford R, et al. Longitudinal study of predictive factors for periodontal disease and tooth loss. J Clin Periodontol. 1999;26:374–80.

    PubMed  CAS  Google Scholar 

  13. 13.

    Rosling B, Serino G, Hellstrom MK, Socransky SS, Lindhe J. Longitudinal periodontal tissue alterations during supportive therapy. Findings from subjects with normal and high susceptibility to periodontal disease. J Clin Periodontol. 2001;28:241–9.

    PubMed  CAS  Google Scholar 

  14. 14.

    Demmer RT, Papapanou PN. Epidemiologic patterns of chronic and aggressive periodontitis. Periodontol 2000. 2010;53:28–44.

    PubMed  Google Scholar 

  15. 15.

    Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC, Beck JD. Periodontal disease at the biofilm-gingival interface. J Periodontol. 2007;78:1911–25.

    PubMed  CAS  Google Scholar 

  16. 16.

    • Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91:914–20. This is a thorough appraisal of current epidemiologic estimates of periodontitis.

    PubMed  CAS  Google Scholar 

  17. 17.

    Kulekci G, Leblebicioglub B, Keskina F, Ciftcia S, Badurc S. Salivary detection of periodontopathic bacteria in periodontally healthy children. Anaerobe. 2008;14:49–54.

    PubMed  CAS  Google Scholar 

  18. 18.

    Preus HR, Zambon JJ, Dunford RG, Genco RJ. The distribution and transmission of Actinobacillus actinomycetemcomitans in families with established adult periodontitis. J Periodontol. 1994;65:2–7.

    PubMed  CAS  Google Scholar 

  19. 19.

    Papapanou PN, Neiderud AM, Disick E, Lalla E, Miller GC, Dahlen G. Longitudinal stability of serum immunoglobulin G responses to periodontal bacteria. J Clin Periodontol. 2004;31:985–90.

    PubMed  CAS  Google Scholar 

  20. 20.

    Joshipura K, Zevallos JC, Ritchie CS. Strength of evidence relating periodontal disease and atherosclerotic disease. Compend Contin Educ Dent. 2009;30:430–9.

    PubMed  Google Scholar 

  21. 21.

    Kebschull M, Demmer RT, Papapanou PN. "Gum bug, leave my heart alone!"–epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res. 2010;89:879–902.

    PubMed  CAS  Google Scholar 

  22. 22.

    Pussinen PJ, Alfthan G, Jousilahti P, Paju S, Tuomilehto J. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis. 2007;193:222–8.

    PubMed  CAS  Google Scholar 

  23. 23.

    Pussinen PJ, Alfthan G, Rissanen H, Reunanen A, Asikainen S, Knekt P. Antibodies to periodontal pathogens and stroke risk. Stroke. 2004;35:2020–3.

    PubMed  Google Scholar 

  24. 24.

    Johansson A, Johansson I, Eriksson M, Ahren AM, Hallmans G, Stegmayr B. Systemic antibodies to the leukotoxin of the oral pathogen Actinobacillus actinomycetemcomitans correlate negatively with stroke in women. Cerebrovasc Dis. 2005;20:226–32.

    PubMed  CAS  Google Scholar 

  25. 25.

    Ford PJ, Gemmell E, Timms P, Chan A, Preston FM, Seymour GJ. Anti-P. gingivalis response correlates with atherosclerosis. J Dent Res. 2007;86:35–40.

    PubMed  CAS  Google Scholar 

  26. 26.

    Desvarieux M, Demmer RT, Rundek T, et al. Periodontal microbiota and carotid intima-media thickness: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). Circulation. 2005;111:576–82.

    PubMed  Google Scholar 

  27. 27.

    Luchsinger JA, Mayeux R. Cardiovascular risk factors and Alzheimer's disease. Curr Atheroscler Rep. 2004;6:261–6.

    PubMed  Google Scholar 

  28. 28.

    Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005;65:545–51.

    PubMed  CAS  Google Scholar 

  29. 29.

    Leibson CL, Rocca WA, Hanson VA, et al. Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol. 1997;145:301–8.

    PubMed  CAS  Google Scholar 

  30. 30.

    Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999;53:1937–42.

    PubMed  CAS  Google Scholar 

  31. 31.

    Peila R, Rodriguez BL, Launer LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study. Diabetes. 2002;51:1256–62.

    PubMed  CAS  Google Scholar 

  32. 32.

    Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol. 2001;154:635–41.

    PubMed  CAS  Google Scholar 

  33. 33.

    Cheng D, Noble J, Tang MX, Schupf N, Mayeux R, Luchsinger JA. Type 2 diabetes and late-onset Alzheimer's disease. Dement Geriatr Cogn Disord. 2011;31:424–30.

    PubMed  CAS  Google Scholar 

  34. 34.

    Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000;356:1627–31.

    PubMed  CAS  Google Scholar 

  35. 35.

    Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141–5.

    PubMed  CAS  Google Scholar 

  36. 36.

    Hofman A, Ott A, Breteler MM, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet. 1997;349:151–4.

    PubMed  CAS  Google Scholar 

  37. 37.

    Ott A, Slooter AJ, Hofman A, et al. Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet. 1998;351:1840–3.

    PubMed  CAS  Google Scholar 

  38. 38.

    Merchant C, Tang MX, Albert S, Manly J, Stern Y, Mayeux R. The influence of smoking on the risk of Alzheimer's disease. Neurology. 1999;52:1408–12.

    PubMed  CAS  Google Scholar 

  39. 39.

    Aggarwal NT, Bienias JL, Bennett DA, et al. The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban community population. Neuroepidemiology. 2006;26:140–6.

    PubMed  Google Scholar 

  40. 40.

    Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346:476–83.

    PubMed  CAS  Google Scholar 

  41. 41.

    Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med. 2003;163:1524–8.

    PubMed  Google Scholar 

  42. 42.

    Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry Jr CP, Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ. 2005;330:1360.

    PubMed  Google Scholar 

  43. 43.

    Rosengren A, Skoog I, Gustafson D, Wilhelmsen L. Body mass index, other cardiovascular risk factors, and hospitalization for dementia. Arch Intern Med. 2005;165:321–6.

    PubMed  Google Scholar 

  44. 44.

    Kalmijn S, Foley D, White L, et al. Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study. Arterioscler, Thromb, Vasc Biol. 2000;20:2255–60.

    CAS  Google Scholar 

  45. 45.

    Gorospe EC, Dave JK. The risk of dementia with increased body mass index: a systematic review. Age Ageing. 2006;36:23–9.

    PubMed  Google Scholar 

  46. 46.

    Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center. Neurology. 2005;64:494–500.

    PubMed  Google Scholar 

  47. 47.

    Langa KM, Foster NL, Larson EB. Mixed dementia: emerging concepts and therapeutic implications. JAMA. 2004;292:2901–8.

    PubMed  CAS  Google Scholar 

  48. 48.

    van Oijen M, de Jong FJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Atherosclerosis and risk for dementia. Ann Neurol. 2007;61:403–10.

    PubMed  Google Scholar 

  49. 49.

    Syrjala AM, Ylostalo P, Ruoppi P, et al. Dementia and oral health among subjects aged 75 years or older. Gerodontology. 2012;29:36–42.

    PubMed  Google Scholar 

  50. 50.

    Yamamoto T, Kondo K, Hirai H, Nakade M, Aida J, Hirata Y. Association between self-reported dental health status and onset of dementia: a 4-year prospective cohort study of older Japanese adults from the Aichi Gerontological Evaluation Study (AGES) Project. Psychosom Med. 2012;74:241–8.

    PubMed  Google Scholar 

  51. 51.

    Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc. 2002;50:430–3.

    PubMed  Google Scholar 

  52. 52.

    Takahashi N, Nyvad B. The role of bacteria in the caries process: ecological perspectives. J Dent Res. 2011;90:294–303.

    PubMed  CAS  Google Scholar 

  53. 53.

    Takahashi N, Nyvad B. Caries ecology revisited: microbial dynamics and the caries process. Caries Res. 2008;42:409–18.

    PubMed  CAS  Google Scholar 

  54. 54.

    Ship JA. Oral health of patients with Alzheimer's disease. J Am Dent Assoc. 1992;123:53–8.

    PubMed  CAS  Google Scholar 

  55. 55.

    Jones JA, Lavallee N, Alman J, Sinclair C, Garcia RI. Caries incidence in patients with dementia. Gerodontology. 1993;10:76–82.

    PubMed  CAS  Google Scholar 

  56. 56.

    Syrjala AM, Ylostalo P, Sulkava R, Knuuttila M. Relationship between cognitive impairment and oral health: results of the Health 2000 Health Examination Survey in Finland. Acta Odontol Scand. 2007;65:103–8.

    PubMed  Google Scholar 

  57. 57.

    Chalmers JM, Carter KD, Spencer AJ. Caries incidence and increments in community-living older adults with and without dementia. Gerodontology. 2002;19:80–94.

    PubMed  CAS  Google Scholar 

  58. 58.

    Stewart R, Hirani V. Dental health and cognitive impairment in an English national survey population. J Am Geriatr Soc. 2007;55:1410–4.

    PubMed  Google Scholar 

  59. 59.

    Grabe HJ, Schwahn C, Volzke H, et al. Tooth loss and cognitive impairment. J Clin Periodontol. 2009;36:550–7.

    PubMed  Google Scholar 

  60. 60.

    Kondo K, Niino M, Shido K. A case–control study of Alzheimer's disease in Japan – significance of life-styles. Dementia. 1994;5:314–26.

    PubMed  CAS  Google Scholar 

  61. 61.

    Okamoto N, Morikawa M, Okamoto K, et al. Tooth loss is associated with mild memory impairment in the elderly: the Fujiwara-kyo study. Brain Res. 2010;1349:68–75.

    PubMed  CAS  Google Scholar 

  62. 62.

    Avlund K, Holm-Pedersen P, Morse DE, Viitanen M, Winblad B. Tooth loss and caries prevalence in very old Swedish people: the relationship to cognitive function and functional ability. Gerodontology. 2004;21:17–26.

    PubMed  Google Scholar 

  63. 63.

    Kaye EK, Valencia A, Baba N, Spiro 3rd A, Dietrich T, Garcia RI. Tooth loss and periodontal disease predict poor cognitive function in older men. J Am Geriatr Soc. 2010;58:713–8.

    PubMed  Google Scholar 

  64. 64.

    Gatz M, Mortimer JA, Fratiglioni L, et al. Potentially modifiable risk factors for dementia in identical twins. Alzheimers Dement. 2006;2:110–7.

    PubMed  Google Scholar 

  65. 65.

    Stein PS, Desrosiers M, Donegan SJ, Yepes JF, Kryscio RJ. Tooth loss, dementia and neuropathology in the Nun study. J Am Dent Assoc. 2007;138:1314–22. quiz 1381–2.

    PubMed  Google Scholar 

  66. 66.

    •• Stein PS, Kryscio RJ, Desrosiers M, Donegan SJ, Gibbs MB. Tooth loss, apolipoprotein E, and decline in delayed word recall. J Dent Res. 2010;89:473–7. This is a rather compelling epidemiologic study of tooth loss predicting memory loss, including APOE effect modification, within a well-described aging cohort (Religious Orders Study).

    PubMed  CAS  Google Scholar 

  67. 67.

    Anderson DJ. Measurement of stress in mastication. I J Dent Res. 1956;35:664–70.

    CAS  Google Scholar 

  68. 68.

    Yurkstas A. The effect of masticatory exercise on the maximum force tolerance of individual teeth. J Dent Res. 1953;32:322–7.

    PubMed  CAS  Google Scholar 

  69. 69.

    Lexomboon D, Trulsson M, Wardh I, Parker MG. Chewing ability and tooth loss: association with cognitive impairment in an elderly population study. J Am Geriatr Soc. 2012;60:1951–6.

    PubMed  Google Scholar 

  70. 70.

    Kim JM, Stewart R, Prince M, et al. Dental health, nutritional status and recent-onset dementia in a Korean community population. Int J Geriatr Psychiatry. 2007;22:850–5.

    PubMed  Google Scholar 

  71. 71.

    Sheiham A, Steele J. Does the condition of the mouth and teeth affect the ability to eat certain foods, nutrient and dietary intake and nutritional status amongst older people? Public Health Nutr. 2001;4:797–803.

    PubMed  CAS  Google Scholar 

  72. 72.

    Walls AW, Steele JG, Sheiham A, Marcenes W, Moynihan PJ. Oral health and nutrition in older people. J Public Health Dent. 2000;60:304–7.

    PubMed  CAS  Google Scholar 

  73. 73.

    Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol. 2006;63:1709–17.

    PubMed  Google Scholar 

  74. 74.

    Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer's disease. Ann Neurol. 2006;59:912–21.

    PubMed  Google Scholar 

  75. 75.

    Krall EA, Garvey AJ, Garcia RI. Alveolar bone loss and tooth loss in male cigar and pipe smokers. J Am Dent Assoc. 1999;130:57–64.

    PubMed  CAS  Google Scholar 

  76. 76.

    Department of Health and Human Services. Oral health in America: a report of the Surgeon General. Rockville: National Institutes of Health, National Institute of Dental and Craniofacial Research; 2000.

    Google Scholar 

  77. 77.

    Hutton B, Feine J, Morais J. Is there an association between edentulism and nutritional state? J Can Dent Assoc. 2002;68:182–7.

    PubMed  Google Scholar 

  78. 78.

    Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent Jr RL. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25:134–44.

    PubMed  CAS  Google Scholar 

  79. 79.

    Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002;15:167–93.

    PubMed  CAS  Google Scholar 

  80. 80.

    Noble JM, Borrell LN, Papapanou PN, Elkind MS, Scarmeas N, Wright CB. Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III. J Neurol Neurosurg Psychiatry. 2009;80:1206–11.

    PubMed  CAS  Google Scholar 

  81. 81.

    Noble J, Scarmeas N, Celentia R, et al. Serum antibodies to periodontal pathogens are associated with incident Alzheimer disease. Alzheimers Dement. 2012;8:498.

    Google Scholar 

  82. 82.

    Sparks Stein P, Steffen MJ, Smith C, et al. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease. Alzheimers Dement. 2012;8:196–203.

    PubMed  CAS  Google Scholar 

  83. 83.

    Kamer AR, Craig RG, Pirraglia E, et al. TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects. J Neuroimmunol. 2009;216:92–7.

    PubMed  CAS  Google Scholar 

  84. 84.

    Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med. 2010;362:329–44.

    PubMed  CAS  Google Scholar 

  85. 85.

    Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ. Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res. 2007;86:306–19.

    PubMed  CAS  Google Scholar 

  86. 86.

    Bodet C, Chandad F, Grenier D. Porphyromonas gingivalis-induced inflammatory mediator profile in an ex vivo human whole blood model. Clin Exp Immunol. 2006;143:50–7.

    PubMed  CAS  Google Scholar 

  87. 87.

    D'Aiuto F, Parkar M, Andreou G, et al. Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res. 2004;83:156–60.

    PubMed  Google Scholar 

  88. 88.

    Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol. 2000;71:1528–34.

    PubMed  CAS  Google Scholar 

  89. 89.

    Wu T, Trevisan M, Genco RJ, Falkner KL, Dorn JP, Sempos CT. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol. 2000;151:273–82.

    PubMed  CAS  Google Scholar 

  90. 90.

    Roberts FA, McCaffery KA, Michalek SM. Profile of cytokine mRNA expression in chronic adult periodontitis. J Dent Res. 1997;76:1833–9.

    PubMed  CAS  Google Scholar 

  91. 91.

    Murata T, Miyazaki H, Senpuku H, Hanada N. Periodontitis and serum interleukin-6 levels in the elderly. Jpn J Infect Dis. 2001;54:69–71.

    PubMed  CAS  Google Scholar 

  92. 92.

    Bretz WA, Weyant RJ, Corby PM, et al. Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population. J Am Geriatr Soc. 2005;53:1532–7.

    PubMed  Google Scholar 

  93. 93.

    Dye BA, Choudhary K, Shea S, Papapanou PN. Serum antibodies to periodontal pathogens and markers of systemic inflammation. J Clin Periodontol. 2005;32:1189–99.

    PubMed  CAS  Google Scholar 

  94. 94.

    Colombo AP, Boches SK, Cotton SL, et al. Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. J Periodontol. 2009;80:1421–32.

    PubMed  CAS  Google Scholar 

  95. 95.

    Schmidt AM, Weidman E, Lalla E, et al. Advanced glycation endproducts (AGEs) induce oxidant stress in the gingiva: a potential mechanism underlying accelerated periodontal disease associated with diabetes. J Periodontal Res. 1996;31:508–15.

    PubMed  CAS  Google Scholar 

  96. 96.

    Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol. 2011;7:738–48.

    PubMed  CAS  Google Scholar 

  97. 97.

    Elter JR, Hinderliter AL, Offenbacher S, et al. The effects of periodontal therapy on vascular endothelial function: a pilot trial. Am Heart J. 2006;151:47.

    PubMed  Google Scholar 

  98. 98.

    Paraskevas S, Huizinga JD, Loos BG. A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol. 2008;35:277–90.

    PubMed  CAS  Google Scholar 

  99. 99.

    Tonetti MS, D'Aiuto F, Nibali L, et al. Treatment of periodontitis and endothelial function. N Engl J Med. 2007;356:911–20.

    PubMed  CAS  Google Scholar 

  100. 100.

    Seinost G, Wimmer G, Skerget M, et al. Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis. Am Heart J. 2005;149:1050–4.

    PubMed  Google Scholar 

  101. 101.

    Mercanoglu F, Oflaz H, Oz O, et al. Endothelial dysfunction in patients with chronic periodontitis and its improvement after initial periodontal therapy. J Periodontol. 2004;75:1694–700.

    PubMed  Google Scholar 

  102. 102.

    Armitage GC. Periodontal infections and cardiovascular disease—how strong is the association? Oral Dis. 2000;6:335–50.

    PubMed  CAS  Google Scholar 

  103. 103.

    Janket SJ, Baird AE, Chuang SK, Jones JA. Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:559–69.

    PubMed  Google Scholar 

  104. 104.

    Cueto A, Mesa F, Bravo M, Ocana-Riola R. Periodontitis as risk factor for acute myocardial infarction. A case control study of Spanish adults. J Periodontal Res. 2005;40:36–42.

    PubMed  CAS  Google Scholar 

  105. 105.

    Behle JH, Papapanou PN. Periodontal infections and atherosclerotic vascular disease: an update. Int Dent J. 2006;56:256–62.

    PubMed  Google Scholar 

  106. 106.

    Takeda M, Ojima M, Yoshioka H, et al. Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients. J Periodontol. 2006;77:15–20.

    PubMed  CAS  Google Scholar 

  107. 107.

    Shlossman M, Knowler WC, Pettitt DJ, Genco RJ. Type 2 diabetes mellitus and periodontal disease. J Am Dent Assoc. 1990;121:532–6.

    PubMed  CAS  Google Scholar 

  108. 108.

    Lalla E, Kaplan S, Chang SM, et al. Periodontal infection profiles in type 1 diabetes. J Clin Periodontol. 2006;33:855–62.

    PubMed  CAS  Google Scholar 

  109. 109.

    Craft S. Insulin resistance syndrome and Alzheimer's disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging. 2005;26 Suppl 1:65–9.

    PubMed  Google Scholar 

  110. 110.

    de Luca C, Olefsky JM. Inflammation and insulin resistance. FEBS Lett. 2008;582:97–105.

    PubMed  Google Scholar 

  111. 111.

    Singer G, Granger DN. Inflammatory responses underlying the microvascular dysfunction associated with obesity and insulin resistance. Microcirculation. 2007;14:375–87.

    PubMed  CAS  Google Scholar 

  112. 112.

    Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131:1557–66.

    PubMed  CAS  Google Scholar 

  113. 113.

    Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135–43.

    PubMed  CAS  Google Scholar 

  114. 114.

    Hansson GK, Robertson AK, Soderberg-Naucler C. Inflammation and atherosclerosis. Annu Rev Pathol. 2006;1:297–329.

    PubMed  CAS  Google Scholar 

  115. 115.

    DeGraba TJ. Immunogenetic susceptibility of atherosclerotic stroke: implications on current and future treatment of vascular inflammation. Stroke. 2004;35:2712–9.

    PubMed  CAS  Google Scholar 

  116. 116.

    Noble JM, Manly JJ, Schupf N, Tang MX, Mayeux R, Luchsinger JA. Association of C-reactive protein with cognitive impairment. Arch Neurol. 2010;67:87–92.

    PubMed  Google Scholar 

  117. 117.

    Kato T, Usami T, Noda Y, Hasegawa M, Ueda M, Nabeshima T. The effect of the loss of molar teeth on spatial memory and acetylcholine release from the parietal cortex in aged rats. Behav Brain Res. 1997;83:239–42.

    PubMed  CAS  Google Scholar 

  118. 118.

    Gobel S. An electron microscopic analysis of the trans-synaptic effects of peripheral nerve injury subsequent to tooth pulp extirpations on neurons in laminae I and II of the medullary dorsal horn. J Neurosci. 1984;4:2281–90.

    PubMed  CAS  Google Scholar 

  119. 119.

    Gobel S, Binck JM. Degenerative changes in primary trigeminal axons and in neurons in nucleus caudalis following tooth pulp extirpations in the cat. Brain Res. 1977;132:347–54.

    PubMed  CAS  Google Scholar 

  120. 120.

    Yamazaki K, Wakabayashi N, Kobayashi T, Suzuki T. Effect of tooth loss on spatial memory and trkB-mRNA levels in rats. Hippocampus. 2008;18:542–7.

    PubMed  CAS  Google Scholar 

  121. 121.

    Watanabe K, Tonosaki K, Kawase T, et al. Evidence for involvement of dysfunctional teeth in the senile process in the hippocampus of SAMP8 mice. Exp Gerontol. 2001;36:283–95.

    PubMed  CAS  Google Scholar 

  122. 122.

    Onozuka M, Watanabe K, Mirbod SM, et al. Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice. Brain Res. 1999;826:148–53.

    PubMed  CAS  Google Scholar 

  123. 123.

    Onozuka M, Watanabe K, Nagasaki S, et al. Impairment of spatial memory and changes in astroglial responsiveness following loss of molar teeth in aged SAMP8 mice. Behav Brain Res. 2000;108:145–55.

    PubMed  CAS  Google Scholar 

  124. 124.

    Watanabe K, Ozono S, Nishiyama K, et al. The molarless condition in aged SAMP8 mice attenuates hippocampal Fos induction linked to water maze performance. Behav Brain Res. 2002;128:19–25.

    PubMed  CAS  Google Scholar 

  125. 125.

    Oue H, Miyamoto Y, Okada S, Koretake K, Michikawa M, Akagawa Y. Tooth loss induces memory impairment and neuronal cell loss in APP transgenic mice. Behav Brain Res. 2013;252:318–25.

    PubMed  CAS  Google Scholar 

  126. 126.

    Ishida N, Ishihara Y, Ishida K, et al. Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice. Poster session presented at: Alzheimer's Association International Conference; 2013 Jul 17; Boston.

Download references

Acknowledgments

James M. Noble has received grant support from the Taub Institute (internal funding mechanism), and some of the prior research described was supported through this grant. He has also received grant support from the National Institute of Dental and Craniofacial Research. Nikolaos Scarmeas has received grant support from the National Institute on Aging (grant AG028506) and the Alzheimer’s Association (grant IIRG-04-1353).

Compliance with ethics Guidelines

Conflict of Interest

James M. Noble has received honoraria from Barclays for a single consulting event regarding intravenous immunoglobulin as an AD therapeutic (the trial has since been reported as a failure).

Nikolaos Scarmeas and Panos N. Papapanou declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Affiliations

Authors

Corresponding author

Correspondence to James M. Noble.

Additional information

This article is part of the Topical Collection on Dementia

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Noble, J.M., Scarmeas, N. & Papapanou, P.N. Poor Oral Health as a Chronic, Potentially Modifiable Dementia Risk Factor: Review of the Literature. Curr Neurol Neurosci Rep 13, 384 (2013). https://doi.org/10.1007/s11910-013-0384-x

Download citation

Keywords

  • Periodontitis
  • Periodontal disease
  • Tooth loss
  • Oral health
  • Caries
  • Dentures
  • Alzheimer disease
  • Cerebrovascular disease
  • Vascular dementia
  • Dementia
  • Epidemiology