CoChat
Sign Up
Cited by 47Oral microbiology and periodontitis researchDental Health and Care UtilizationDementia and Cognitive Impairment Research

Oral Health Status in Subjects with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Data from the Zabút Aging Project

Open access
Panzarella, Vera, Mauceri, Rodolfo, Baschi, Roberta, Maniscalco, Laura, Campisi, Giuseppina, Monastero, Roberto·2022·Journal of Alzheimer's Disease
DOI 10.3233/jad-200385PMC PMC9277678
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: The relationship between Alzheimer’s disease (AD) and periodontitis has been recently investigated with heterogenous results. Objective: This study aims to evaluate the oral health status and its relationship with cognitive impairment of participants, enrolled in the Zabút Aging Project, a community-based cohort study performed in a rural community in Sicily, Italy. Methods: A case-control study (20 subjects with AD, 20 with amnestic mild cognitive impairment [aMCI], and 20 controls) was conducted. The protocol included a comprehensive medical and cognitive-behavioral examination. Full-mouth evaluation, microbial analysis of subgingival plaque samples (by RT-PCR analysis), and oral health-related quality of life (OHR-QoL) were evaluated. Results: The decayed, missing, and filled teeth (DMFT) total score of AD subjects was significantly higher than aMCI (p = 0.009) and controls (p = 0.001). Furthermore, the “M” component of DMFT (i.e., the number of missing teeth) was significantly higher in AD than in aMCI (p < 0.001) and controls (p < 0.001). A Poisson regression model revealed that age (p < 0.001), male gender (p = 0.001), and AD (p = 0.001) were positively correlated with DMFT. Concerning oral microbial load, the presence of Fusobacterium nucleatum was significantly higher in AD than in controls (p = 0.02), and a higher load of Treponema denticola was found in aMCI than with AD (p = 0.004). OHR-QoL scores did not differ among the groups. Conclusion: The current research suggests that AD is associated with chronic periodontitis, which is capable of determining tooth loss due to the pathogenicity of Fusobacterium nucleatum. These data remain to be confirmed in larger population-based cohorts.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3233/jad-200385

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Although mucosa copy numbers of Campylobacter rectus and Treponema denticola are unrelated to AD risk, titer levels of these pathogens are linked to increased risk of ACD.

    “Although mucosa copy numbers of Campylobacter rectus and Treponema denticola are unrelated to AD risk, titer levels of these pathogens are linked to increased risk of ACD [74,75].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [75]

    The Discussion (page unavailable) says a cited study found no significant differences in antibody levels against selected bacteria, including Treponema denticola, between groups—contrary to the claimed link between pathogen titers and increased risk. The Results report a higher T. denticola oral load in aMCI than in AD, while the Methods do not list Campylobacter rectus among the organisms tested. The paper does not establish the claimed pattern for both pathogens. (LLM, conf=0.86)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • P. gingivalis titers (or mucosa copy numbers) have not been related to performance in the MMSE or ADAS-cog, nor a risk of AD or ACD.

    “However, P. gingivalis titers (or mucosa copy numbers) have not been related to performance in the MMSE or ADAS-cog, nor a risk of AD or ACD [73–75].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [75]

    Results, Table 3, and the Discussion report no significant difference in subgingival P. gingivalis load among controls, aMCI, and AD groups. The paper reports MMSE scores separately but does not test their relationship to P. gingivalis load; it does not report ADAS-cog results or assess future risk of AD or ACD. Its group comparison therefore supports only part of the attributed claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Mucosa copy numbers of Fusobacterium nucleatum have been related to increased AD, and evidence suggests lower titers of Actinomyces naeslundii in AD.

    “Mucosa copy numbers of Fusobacterium nucleatum have been related to increased AD, and evidence suggests lower titers of Actinomyces naeslundii in AD [74,75].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [75]

    The Results and Discussion report significantly higher Fusobacterium nucleatum load in AD subjects than in controls. However, the Methods specify subgingival plaque sampling, not mucosal sampling, and list the organisms tested without Actinomyces naeslundii. This source therefore does not support the claim about lower A. naeslundii titers in AD. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Mucosa copy number or serum titers of Tannerella forsythia and Aggregatibacter actinomycetemcomitans have not been associated with a risk of AD or ACD.

    “Mucosa copy number or serum titers of other common periodontal bacteria, such as Tannerella forsythia and Aggregatibacter actinomycetemcomitans, have not been associated with a risk of AD or ACD [74,75].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [75]

    Table 3 in the Results reports no significant differences in subgingival-plaque bacterial loads for Tannerella forsythia or Aggregatibacter actinomycetemcomitans among the AD, aMCI, and control groups. The paper does not report serum titers for these species or assess their association with future risk of AD or ACD; it compares existing diagnostic groups. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 56

  1. [1]World Health Organization (2015) World Report on Ageing and Health. pp. 1– 247.
  2. [2]Centers for Disease Control and Prevention (CDC) (2003) Trends in aging— United States and worldwide. MMWR Morb Mortal Wkly Rep 52, 101– 104, 106. 12645839
  3. [3]Di Fiandra T, Canevelli M, Di Pucchio A, Vanacore N, Italian Dementia National Plan Working Group (2015) The Italian Dementia National Plan. Commentary.á. Ann Ist Super Sanit 51, 261– 264. 26783209
  4. [4]Scheltens P, Blennow K, Breteler MMB, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM (2016) Alzheimer’s disease. Lancet 388, 505– 517. 26921134
  5. [5]Monastero R, Caruso C, Vasto S (2014) Alzheimer’s disease and infections, where we stand and where we go. Immun Ageing 11, 1– 4. 25535510 PMC4273443
  6. [6]Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund L-O, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment - beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256, 240– 246. 15324367
  7. [7]Mariani E, Monastero R, Mecocci P (2007) Mild cognitive impairment: a systematic review. J Alzheimers Dis 12, 23– 35. 17851192
  8. [8]Monastero R, Mangialasche F, Camarda C, Ercolani S, Camarda R (2009) A systematic review of neuropsychiatric symptoms in mild cognitive impairment. J Alzheimers Dis 18, 11– 30. 19542627
  9. [9]Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7, 270– 279. 21514249 PMC3312027
  10. [11]Tonsekar PP, Jiang SS, Yue G (2017) Periodontal disease, tooth loss and dementia: Is there a link? A systematic review. Gerodontology 34, 151– 163. 28168759
  11. [12]Lexomboon D, Trulsson M, Wãrdh I, Parker MG (2012) Chewing ability and tooth loss: Association with cognitive impairment in an elderly population study. J Am Geriatr Soc 60, 1951– 1956. 23035667
  12. [13]Noble JM, Scarmeas N, Papapanou PN (2013) Poor oral health as a chronic, potentially modifiable dementia risk factor: review of the literature. Curr Neurol Neurosci Rep 13, 384. 23963608 PMC6526728
  13. [14]Tonetti MS, Bottenberg P, Conrads G, Eickholz P, Heasman P, Huysmans M-C, López R, Madianos P, Müller F, Needleman I, Nyvad B, Preshaw PM, Pretty I, Renvert S, Schwendicke F, Trombelli L, van der Putten G-J, Vanobbergen J, West N, Young A, Paris S (2017) Dental caries and periodontal diseases in the ageing population: call to action to protect and enhance oral health and well-being as an essential component of healthy ageing - Consensus report of group 4 of the joint EFP/ORCA workshop on the boundaries be. J Clin Periodontol 44, S135– S144. 28266112
  14. [15]Gil-Montoya JA, Sánchez-Lara I, Carnero-Pardo C, Fornieles-Rubio F, Montes J, Barrios R, Gonzalez-Moles MA, Bravo M (2016) Oral hygiene in the elderly with different degrees of cognitive impairment and dementia. J Am Geriatr Soc 65, 642– 647. 28024093
  15. [16]Zuluaga DJM, Montoya JAG, Contreras CI, Herrera RR (2012) Association between oral health, cognitive impairment and oral health-related quality of life. Gerodontology 29, 667– 673. 21883423
  16. [17]Martande SS, Pradeep AR, Singh SP, Kumari M, Suke DK, Raju AP, Naik SB, Singh P, Guruprasad CN, Chatterji A (2014) Periodontal health condition in patients with Alzheimer’s disease. Am J Alzheimers Dis Other Demen 29, 498– 502. 25214647 PMC10852660
  17. [18]Highfield J (2009) Diagnosis and classification of periodontal disease. Aust Dent J 54(Suppl 1), S11– 26. 19737262
  18. [19]Burt B, Research, Science and Therapy Committee of the American Academy of Periodontology (2005) Position paper - Epidemiology of periodontal diseases. J Periodontol 76, 1406– 1419. 16101377
  19. [21]Beck JD, Sharp T, Koch GG, Offenbacher S (1997) A 5-year study of attachment loss and tooth loss in community-dwelling older adults. J Periodontal Res 32, 516– 523. 9379319
  20. [22]Pizzo G, Guiglia R, Russo L Lo, Campisi G (2010) Dentistry and internal medicine: from the focal infection theory to the periodontal medicine concept. Eur J Intern Med 21, 496– 502. 21111933
  21. [23]Olsen I, Singhrao SK (2015) Can oral infection be a risk factor for Alzheimer’s disease? J Oral Microbiol 7, 1– 16. PMC4575419 26385886
  22. [24]Cestari JAF, Fabri GMC, Kalil J, Nitrini R, Jacob-Filho W, De Siqueira JTT, Siqueira SRDT (2016) Oral infections and cytokine levels in patients with Alzheimer’s disease and mild cognitive impairment compared with controls. J Alzheimers Dis 52, 1479– 1485. 27104907
  23. [25]Scannapieco FA, Cantos A (2016) Oral inflammation and infection, and chronic medical diseases: implications for the elderly. Periodontol 2000 72, 153– 175. 27501498
  24. [26]Fiorillo L, Cervino G, Laino L, D’Amico C, Mauceri R, Tozum TF, Gaeta M, Cicciú M (2019) Porphyromonas gingivalis, periodontal and systemic implications: a systematic review. Dent J 7, 114. PMC6960968 31835888
  25. [27]Carlesimo GA, Caltagirone C, Gainotti G, Fadda L, Gallassi R, Lorusso S, Marfia G, Marra C, Nocentini U, Parnetti L (1996) The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. Eur Neurol 36, 378– 384. 8954307
  26. [29]McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7, 263– 269. 21514250 PMC3312024
  27. [30]Grigoletto F, Zappalá G, Anderson DW, Lebowitz BD (1999) Norms for the Mini-Mental State Examination in a healthy population. Neurology 53, 315– 320. 10430420
  28. [31]Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW (1963) Studies of illness in the aged: the index of ADL: A standardized measure of biological and psychosocial function. JAMA 185, 914– 919. 14044222
  29. [32]Lawton MP, Brody EM (1969) Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 9, 179– 186. 5349366
  30. [34]Marino Gammazza A, Restivo V, Baschi R, Caruso Bavisotto C, Cefalú AB, Accardi G, Conway de Macario E, Macario AJL, Cappello F, Monastero R (2018) Circulating molecular chaperones in subjects with amnestic mild cognitive impairment and Alzheimer’s disease: data from the Zabút Aging Project. J Alzheimers Dis, doi: 10.3233/JAD-180825. PMC9277667 30584145 · DOI
  31. [35]Cook Z, Kirk S, Lawrenson S, Sandford S (2005) Use of BMI in the assessment of undernutrition in older subjects: reflecting on practice. Proc Nutr Soc 64, 313– 317. 16048662
  32. [36]Monastero R, Cefalú AB, Camarda C, Buglino CM, Mannino M, Barbagallo CM, Lopez G, Camarda LKC, Travali S, Camarda R, Averna MR (2003) No association between Glu298Asp endothelial nitric oxide synthase polymorphism and Italian sporadic Alzheimer’s disease. Neurosci Lett 341, 229– 232. 12697290
  33. [37]Petersen PE, Baez RJ, WHO (2013), Oral Health Surveys Basic Methods - Fifth Edition.
  34. [38]Landry RG, Jean M (2002) Periodontal Screening and Recording (PSR) Index: precursors, utility and limitations in a clinical setting. Int Dent J 52, 35– 40. 11931220
  35. [39]Corridore D, Campus G, Guerra F, Ripari F, Sale S, Ottolenghi L (2013) Validation of the Italian version of the Oral Health Impact Profile-14 (IOHIP-14). Ann Stomatol (Roma) 4, 239– 243. 24611088 PMC3935349
  36. [40]Arrivè E, Letenneur L, Matharan F, Laporte C, Helmer C, Barberger-Gateau P, Miquel JL, Dartigues JF (2012) Oral health condition of French elderly and risk of dementia: A longitudinal cohort study. Community Dent Oral Epidemiol 40, 230– 238. 22059867
  37. [41]Ide M, Harris M, Stevens A, Sussams R, Hopkins V, Culliford D, Fuller J, Ibbett P, Raybould R, Thomas R, Puenter U, Teeling J, Perry VH, Holmes C (2016) Periodontitis and cognitive decline in Alzheimer’s disease. PLoS One 11, e0151081. 26963387 PMC4786266
  38. [42]Chen C-K, Wu Y-T, Chang Y-C (2017) Association between chronic periodontitis and the risk of Alzheimer’s disease: a retrospective, population-based, matched-cohort study. Alzheimers Res Ther 9, 56. 28784164 PMC5547465
  39. [43]Nilsson H, Sanmartin Berglund J, Renvert S (2018) Longitudinal evaluation of periodontitis and development of cognitive decline among older adults. J Clin Periodontol 45, 1142– 1149. 30076762
  40. [44]Nilsson H, Berglund JS, Renvert S (2018) Periodontitis, tooth loss and cognitive functions among older adults. Clin Oral Investig 22, 2103– 2109. 29270902
  41. [45]Iwasaki M, Kimura Y, Ogawa H, Yamaga T, Ansai T, Wada T, Sakamoto R, Ishimoto Y, Fujisawa M, Okumiya K, Miyazaki H, Matsubayashi K (2018) Periodontitis, periodontal inflammation, and mild cognitive impairment: A 5-year cohort study. J Periodontal Res 54, 233– 240. 30345659
  42. [46]Iwasaki M, Yoshihara A, Kimura Y, Sato M, Wada T, Sakamoto R, Ishimoto Y, Fukutomi E, Chen W, Imai H, Fujisawa M, Okumiya K, Taylor GW, Ansai T, Miyazaki H, Matsubayashi K (2016) Longitudinal relationship of severe periodontitis with cognitive decline in older Japanese. J Periodontal Res 51, 681– 868. 26740384
  43. [47]Dioguardi M, Di Gioia G, Caloro GA, Capocasale G, Zhurakivska K, Troiano G, Lo Russo L, Lo Muzio L (2019) The association between tooth loss and Alzheimer’s disease: a systematic review with meta-analysis of case control studies. Dent J (Basel) 7, 49. PMC6630622 31052367
  44. [48]Riviere GR, Riviere KH, Smith KS (2002) Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol 17, 113– 118. 11929559
  45. [49]Poole S, Singhrao SK, Kesavalu L, Curtis MA, Crean S (2013) Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J Alzheimers Dis 36, 665– 677. 23666172
  46. [50]Sochocka M, Zwolińska K, Leszek J (2017) The infectious etiology of Alzheimer’s disease. Curr Neuropharmacol 15, 996– 1009. 28294067 PMC5652018
  47. [51]Han YW (2015) Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 23, 141– 147. 25576662 PMC4323942
  48. [53]Kaplan CW, Lux R, Haake SK, Shi W (2009) Theouter membrane protein RadD is an arginine-inhibitable adhesin required for inter-species adherence and the structured architecture of multispecies biofilm. Mol Microbiol 71, 35– 47. 19007407 PMC2741168
  49. [54]Chaushu S, Wilensky A, Gur C, Shapira L, Elboim M, Halftek G, Polak D, Achdout H, Bachrach G, Mandelboim O (2012) Direct recognition of Fusobacterium nucleatum by the NK cell natural cytotoxicity receptor NKp46 aggravates periodontal disease. PLoS Pathog 8, e1002601. 22457623 PMC3310798
  50. [55]Riviere GR, Smith KS, Carranza N, Tzagaroulaki E, Kay SL, Dock M (1995) Subgingival distribution of Treponema denticola, Treponema socranskii, and pathogen-related oral spirochetes: prevalence and relationship to periodontal status of sampled sites. J Periodontol 66, 829– 837. 8537864
  51. [56]Sadrameli M, Bathini P, Alberi L (2020) Linking mechanisms of periodontitis to Alzheimer’s disease. Curr Opin Neurol 33, 230– 238. 32097126
  52. [57]Laugisch O, Johnen A, Maldonado A, Ehmke B, Bürgin W, Olsen I, Potempa J, Sculean A, Duning T, Eick S (2018) Periodontal pathogens and associated intrathecal antibodies in early stages of Alzheimer’s disease. J Alzheimers Dis 66, 105– 114. 30223397
  53. [58]Ming Y, Hsu S-W, Yen Y-Y, Lan S-J (2019) Association of oral health–related quality of life and Alzheimer disease: A systematic review. J Prosthet Dent, doi; 10.1016/j.prosdent.2019.08.015. 31753458 · DOI
  54. [59]Lunet N, Azevedo A (2009) On the comparability of population-based and hospital-based case-control studies. Gac Sanit 23, 564. 19647901
  55. [60]Nascimento PC, Castro MML, Magno MB, Almeida APCPSC, Fagundes NCF, Maia LC, Lima RR (2019) Association between periodontitis and cognitive impairment in adults: a systematic review. Front Neurol 10, 323. 31105630 PMC6492457
  56. [61]Choi S, Kim K, Chang J, Kim SM, Kim SJ, Cho HJ, Park SM (2019) Association of chronic periodontitis on Alzheimer’s disease or vascular dementia. J Am Geriatr Soc 67, 1234– 1239. 30874308

Cited by

Sorted by citations

Authors
Panzarella, V., Mauceri, R., Baschi, R., Maniscalco, L., Campisi, G., & Monastero, R.
Affiliations
University of Palermo (IT)
Corresponding author
Monastero, Roberto
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2022-05-03
Volume
87
Issue
1
Pages
173-183
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-200385
PMC
PMC9277678
OpenAlex
W3034049776
Cited by
47
References
3
Citations by year
2026: 6 · 2025: 15 · 2024: 10 · 2023: 9 · 2022: 3 · 2021: 3 · 2020: 1
FWCI
4.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
Funders
  • Ministero della Salute
  • Università degli Studi di Palermo
Topics
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Health Sciences › Dentistry › Periodontics › Dental Health and Care Utilization
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, amnestic mild cognitive impairment
MeSH terms
Aging, Alzheimer Disease, Humans, Male, Neuropsychological Tests, Oral Health, Quality of Life, Cohort Studies, Case-Control Studies, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review