Main Article Content
Individuals with Down syndrome (DS) are known to be highly susceptible to periodontal disease, exhibiting a rapid progression and increased severity in younger age. They are also at high risk for Alzheimer’s disease (AD) with certain risk derived from amyloid-β (Aβ) accumulation. Periodontal disease in DS individuals is related to an impaired immune system, poor oral hygiene, gingival tissue abnormalities, salivary factors, microbial factors and oxidative stress with high levels of radical oxygen resulting in genetic abnormalities. However, simultaneous assessments of these factors were not performed to clear risk factors to periodontal disease in DS individuals. This study investigated relationships among various parameters in oral and systemic diseases in DS and non-DS subjects.
Thirty DS subjects and 38 non-DS subjects were enrolled in this study and their oral hygiene and oral disease status were examined. Unstimulated whole saliva and blood samples were collected to investigate the presence of periodontal bacteria, cariogenic bacteria and opportunistic pathogens; interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α saliva concentrations; and Aβ42 plasma concentrations. Among tested parameters, Aβ42 plasma concentrations, development of periodontal diseases, S. mutans rate, lactobacilli per total streptococci ratio, numbers of Candida and IL-6 and IL-8 saliva concentrations were significantly higher in DS subjects than in control subjects. Additionally, oral disease parameters, except for the decay-missing-filled index, were significantly higher in DS subjects than control subjects. However, no significant difference was observed in periodontal bacteria ratios between DS and control subjects.
Our results demonstrate that DS subjects are more likely to develop periodontal diseases, produce inflammatory cytokines and become infected by opportunistic pathogens in the oral cavity than control subjects. This is likely due to poor oral hygiene and decreased host defense responses rather than infection of pathogenic bacteria or Aβ accumulation.
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
1. Alonso R, Pisa D, Marina AI, Morato E, Rábano A, Carrasco L. Fungal infection in patients with Alzheimer’s disease. J Alzheimers Dis. 2014; 41(1): 301-11.
2. Alonso R, Pisa D, Rábano A, Carrasco L. Alzheimer’s disease and disseminated mycoses. Eur J Clin Microbiol Infect Dis. 2014; 33(7): 1125-32.
3. Amano A, Kishima T, Kimura S, Takiguchi M, Ooshima T, Hamada S, Morisaki I. Periodontopathic bacteria in children with Down syndrome. J Periodontol. 2000; 71(2): 249-55.
4. Amano A, Murakami J, Akiyama S, Morisaki I. Etiologic factors of early-onset periodontal disease in Down syndrome. Japanese Dental Science Review. 2008; 44(2): 118-27.
5. Areias C, Sampaio-Maia B, Macho V, Leal I, Melo P, de Andrade C. Does the chemistry in the saliva of Down syndrome children explain their low caries prevalence? Eur J Paediatr Dent. 2013; 14(1): 23-6.
6. Axelsson P, Nyström B, Lindhe J. The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance. J Clin Periodontol. 2004; 31(9): 749-57.
7. Barr-Agholme M, Krekmanova L, Yucel-Lindberg T, Shinoda K, Modéer T. Prostaglandin E2 level in gingival crevicular fluid from patients with Down syndrome. Acta Odontol Scand. 1997; 55(2): 101-5.
8. Carlstedt K, Krekmanova L, Dahllöf G, Ericsson B, Braathen G, Modéer T. Oral carriage of Candida species in children and adolescents with Down's syndrome. Int J Paediatr Dent. 1996; 6 (2): 95-100.
9. Cichon P, Crawford L, Grimm WD. Early-onset periodontitis associated with Down’s syndrome--clinical interventional study. Ann Periodontol. 1998; 3(1): 370-80.
10. Cosentino SA, Stern Y, Sokolov E, Scarmeas N, Manly JJ, Tang MX, Schupf N, Mayeux RP. Plasma ß-amyloid and cognitive decline. Arch Neurol. 2010; 67(12): 1485-90.
11. Desai SS. Down syndrome: a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997; 84(3): 279-85.
12. Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JC, Breteler MM. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol. 2004; 61(5): 668-72.
13. Ertugrul AS, Sahin H, Dikilitas A, Alpaslan N, Bozoglan A. Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis. J Periodont Res. 2013; 48(1): 44-51.
14. Faria Carrada C, Almeida Ribeiro Scalioni F, Evangelista Cesar D, Lopes Devito K, Ribeiro LC, Almeida Ribeiro R. Salivary periodontopathic bacteria in children and adolescents with Down syndrome. PLoS One. 2016; 11(10): e0162988.
15. Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, Bittles AH. The changing survival profile of people with Down's syndrome: implications for genetic counselling. Clin Genet. 2002; 62 (5): 390-3.
16. Head E, Powell D, Gold BT, Schmitt FA. Alzheimer’s disease in Down syndrome. Eur J Neurodegener Dis. 2012; 1(3): 353-64.
17. Hill DA, Gridley G, Cnattingius S, Mellemkjaer L, Linet M, Adami HO, Olsen JH, Nyren O, Fraumeni JF Jr. Mortality and cancer incidence among individuals with Down syndrome. Arch Intern Med. 2003; 163(6): 705-11.
18. Iwamoto T, Yamada A, Yuasa K, Fukumoto E, Nakamura T, Fujiwara T, Fukumoto S. Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts. Arch Oral Biol. 2009; 54(10): 963-9.
19. Iwatsubo T, Okada A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron.1994; 13(1): 45-53.
20. Khocht A, Russell B, Cannon JG, Turner B, Janal M. Phagocytic cell activity and periodontitis in Down syndrome. Oral Dis. 2012; 18(4): 346–52.
21. Khocht A, Yaskell T, Janal M, Turner BF, Rams TE, Haffajee AD, Socransky SS. Subgingival microbiota in adult Down syndrome periodontitis. J Periodontal Res. 2012; 47(4): 500-7.
22. Larmas M, Makinen KK. Dental caries prevalence and incidence in pediatric dentistry. J Compr Ped. 2015; 6(1): e21174.
23. Lossinsky AS, Shivers RR. Structural pathways for macromolecular and cellular transport across the blood-brain barrier during inflammatory conditions. Review. Histol Histopathol. 2004; 19(2): 535-64.
24. Mahoney FI, Barthel DW. Functional evaluation: The Barthel Index. Maryland State Med J. 1965; 14: 61-5.
25. Margallo-Lana ML, Moore PB, Kay DW, Perry RH, Reid BE, Berney TP, Tyrer SP. Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology. J Intellect Disabil Res. 2007; 51(6): 463-77.
26. Mayeux R, Honig LS, Tang MX, Manly J, Stern Y, Schupf N, Mehta PD. Plasma A[beta]40 and A[beta]42 and Alzheimer’s disease: relation to age, mortality, and risk. Neurology. 2003; 61(9): 1185-90.
27. Mehta PD, Capone G, Jewell A, Freedland RL. Increased amyloid beta protein levels in children and adolescents with Down syndrome. J Neurol Sci. 2007; 254(1-2): 22-7.
28. Mohiddin G, Narayanaswamy AB, Masthan KM, Nagarajan A, Panda A, Behura SS. Oral candidal and streptococcal carriage in Down syndrome patients. J Nat Sci Biol Med. 2015; 6(2): 300-5.
29. Morinushi T, Lopatin DE, Van Poperin N. The relationship between gingivitis and the serum antibodies to the microbiota associated with periodontal disease in children with Down's syndrome. J Periodontol. 1997; 68(7): 626-31.
30. Murakami J, Kato T, Kawai S, Akiyama S, Amano A, Morisaki I. Cellular motility of Down syndrome gingival fibroblasts is susceptible to impairment by porphyromonas gingivalis invasion. J Periodontol. 2008; 79(4): 721-7.
31. Olsen I, Singhrao SK. Can oral infection be a risk factor for Alzheimer’s disease? J Oral Microbiol. 2015; 7: 29143.
32. Orner G. Periodontal disease among children with Down's syndrome and their siblings. J Dent Res. 1976; 55(5): 778-82.
33. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A: National Birth Defects Prevention Network. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010; 88(12): 1008-16.
34. Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med. 2010; 362(4): 329-44.
35. Ram G, Chinen J. Infections and immunodeficiency in Down syndrome. Clin Exp Immunol. 2011; 164(1): 9-16.
36. Reuland-Bosma W, van Dijk J. Periodontal disease in Down’s syndrome: a review. J Clin Periodontal. 1986; 13(1): 64-73.
37. Rumble B, Retallack R, Hilbich C, Simms G, Multhaup G, Martins R, Hockey A, Montgomery P, Beyreuther K, Masters CL. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. N Engl J Med. 1989; 320(22): 1446-52.
38. Sakellari D, Arapostathis KN, Konstantinidis A. Periodontal conditions and subgingival microflora in Down syndrome patients. A case-control study. J Clin Periodontol. 2005; 32(6): 684-90.
39. Schupf N, Sergievsky GH. Genetic and host factors for dementia in Down's syndrome. Br J Psychiatry. 2002; 180: 405-10.
40. Schupf N, Zigman WB, Tang MX, Pang D, Mayeux R, Mehta P, Silverman W. Change in plasma Aβ peptides and onset of dementia in adults with Down syndrome. Neurology. 2010; 75(18): 1639-44.
41. Shweihat Y, Perry J 3rd, Shah D. Isolated Candida infection of the lung. Respir Med Case Rep. 2015; 16:18–9.
42. Toba K, Nakai R, Akishita M, Iijima S, Nishinaga M, Mizoguchi T, Yamada S, Yumita K, Ouchi Y. Vitality Index as useful tool to assess elderly with dementia. Geriatrics & Gerontology International. 2002; 2(1): 23-9.
43. Tsilingaridis G, Yucel-Lindberg T, Modéer T. T-helper-related cytokines in gingival crevicular fluid from adolescents with Down syndrome. Clin Oral Investig. 2012; 16(1): 267–73.
44. Ugazio AG. Down’s syndrome: problems of immunodeficiency. Hum Genet Suppl. 1981; 2: 33-9.
45. van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM. Plasma Abeta(1-40) and Abeta(1-42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol. 2006; 5(8): 655-60.
46. Webb RL, Murphy MP. β-Secretases, Alzheimer’s disease, and Down syndrome. Curr Gerontol Geriatr Res. 2012; 362839.
47. Wei SH, Lang KP. Periodontal epidemiological indices for children and adolescents: I. Gingival and periodontal health assessments. Pediatr Dent. 1981; 3(4): 353-60.
48. Wei SH, Lang NP. Periodontal epidemiological indices for children and adolescents: II. Evaluation of oral hygiene; III. Clinical applications. Pediatr Dent. 1982; 4(1): 64-73.
49. Wisniewski HM, Wegiel J, Popovitch E. Age-associated development of diffuse and thioflavine-S-positive plaques in Down syndrome. Dev Brain Dysfunct. 1994; 7: 330-9.
50. Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985; 17 (3): 278-82.
51. Zhou ZD, Chan CH, Ma QH, Xu XH, Xiao ZC, Tan EK. The roles of amyloid precursor protein (APP) in neurogenesis: Implications to pathogenesis and therapy of Alzheimer disease. Cell Adh Migr. 2011; 5(4): 280-92.