Periodontitis and Cognitive Decline in Alzheimer’s Disease
Open accessAbstract
Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.
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.
Integrity signals
Registry
Cites
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.
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?
High titers of P. gingivalis have been associated with decreased performance in delayed verbal memory as well as serial subtraction, while P. gingivalis seropositivity has been related to decreased ADAS-cog performance.
“High titers of P. gingivalis have been associated with decreased performance in delayed verbal memory as well as serial subtraction, while P. gingivalis seropositivity has been related to decreased ADAS-cog performance [73].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [73]
The Results (Longitudinal follow up; page unavailable) report no significant association between baseline P. gingivalis antibody levels and the rate of ADAS-cog decline. The Discussion reiterates that finding. The paper does not report the claimed delayed verbal memory or serial subtraction associations. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredP. 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 [73]
The Results (Longitudinal follow up; page unavailable) found no significant association between baseline serum P. gingivalis antibody levels and subsequent change in ADAS-cog or sMMSE scores among participants who already had AD. That supports the claim about cognitive decline, but this study did not establish a lack of association with baseline test performance, mucosal copy numbers, or risk of developing AD or ACD. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAlzheimer's disease is accelerated by systemic infections, including gum disease.
“which is accelerated by systemic infections, including gum disease.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [87]
People with chronic gum disease (periodontitis) have elevated blood endotoxin, a higher risk of Alzheimer's disease and a faster rate of cognitive decline.
“People with chronic gum disease (periodontitis) have elevated blood endotoxin [85, 86], a higher risk of Alzheimer’s disease and a faster rate of cognitive decline [87].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [87]
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
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Cohen, J. (1992) · Psychological Bulletin · doi:10.1037//0033-2909.112.1.155 · Cited by 8,771 · see citing works
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175 · see citing works
. Cerebral blood flow in dementia.
Hachinski, V. C., Iliff, L. D., Zilhka, E., Du Boulay, G. H., McAllister, V. L., Marshall, J., Russell, R. W. R., & Symon, L. (1975) · Archives of Neurology · doi:10.1001/archneur.1975.00490510088009 · Cited by 3,186 · see citing works
The Clinical Diagnosis of Alzheimer's Disease
Wade, J. P. H., Mirsen, T. R., Hachinski, V. C., Fisman, M., Lau, C. S., & Merskey, H. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520130016010 · Cited by 1,416 · see citing works
Update of the Case Definitions for Population‐Based Surveillance of Periodontitis
Eke, P. I., Page, R. C., Liang, W., Thornton‐Evans, G. O., & Genco, R. J. (2012) · Journal of Periodontology · doi:10.1902/jop.2012.110664 · Cited by 1,328 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Self-citationA systematic review and meta‐analyses on C‐reactive protein in relation to periodontitis
Paraskevas, S., Huizinga, J. D., & Loos, B. G. (2008) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.2007.01173.x · Cited by 757 · see citing works
Global epidemiology of periodontal diseases: an overview
Albandar, J. M., & Rams, T. E. (2002) · Periodontology 2000 · doi:10.1034/j.1600-0757.2002.290101.x · Cited by 525 · see citing works
A Guide to the Standardized Mini-Mental State Examination
Molloy, D. W., & Standish, T. I. M. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297004754 · Cited by 505 · see citing works
Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease
Stein, P. S., Steffen, M. J., Smith, C. D., Jicha, G. A., Ebersole, J. L., Abner, E. L., & Dawson, D. R. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.04.006 · Cited by 463 · see citing works
Tooth loss, dementia and neuropathology in the Nun Study
Stein, P. S., Desrosiers, M. F., DONEGAN, S. J., Yepes, J. F., & Kryscio, R. J. (2007) · The Journal of the American Dental Association · doi:10.14219/jada.archive.2007.0046 · Cited by 375 · see citing works
Kamer, A. R., Craig, R. G., Pirraglia, E., Dasanayake, A. P., Norman, R. G., Boylan, R. J., Nehorayoff, A., Glodzik, L., Bryś, M., & de Leon, M. J. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.08.013 · Cited by 271 · see citing works
Periodontal disease associates with higher brain amyloid load in normal elderly
Kamer, A. R., Pirraglia, E., Tsui, W., Rusinek, H., Vallabhajosula, S., Mosconi, L., Li, Y., McHugh, P. F., Craig, R. G., Svetcov, S., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.10.038 · Cited by 270 · see citing works
Geerts, S. O., Nys, M., Mol, P. D., Charpentier, J., Albert, A., Legrand, V. M. G., & Rompen, E. (2002) · Journal of Periodontology · doi:10.1902/jop.2002.73.1.73 · Cited by 257 · see citing works
Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease
Noble, J. M., Scarmeas, N., Celenti, R. S., Elkind, M. S. V., Wright, C. B., Schupf, N., & Papapanou, P. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114959 · Cited by 214 · see citing works
Dementia and oral health among subjects aged 75 years or older.
Syrjälä, A.-M. H., Ylöstalo, P., Ruoppi, P., Komulainen, K., Hartikainen, S., Sulkava, R., & Knuuttila, M. (2012) · Gerodontology · doi:10.1111/j.1741-2358.2010.00396.x · Cited by 168 · see citing works
Ide, M., Jagdev, D., Coward, P. Y., Crook, M. A., Barclay, G. R., & Wilson, R. F. (2004) · Journal of Periodontology · doi:10.1902/jop.2004.75.3.420 · Cited by 131 · see citing works
Self-citationPeriodontal Health Condition in Patients With Alzheimer’s Disease
Martande, S., Pradeep, A. R., Singh, S. P., Kumari, M., Suke, D. K., Raju, A. P., Naik, S. B., Singh, P., Guruprasad, C. N., & Chatterji, A. (2014) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317514549650 · Cited by 110 · see citing works
Okamoto, N., Morikawa, M., Tomioka, K., Yanagi, M., Amano, N., & Kurumatani, N. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141665 · Cited by 109 · see citing works
Serum levels of interleukin‐10 and tumour necrosis factor‐α in chronic periodontitis
Passoja, A., Puijola, I., Knuuttila, M. L. E., Niemelä, O. J., Karttunen, R. A., Raunio, T., & Tervonen, T. (2010) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2010.01602.x · Cited by 98 · see citing works
Periodontal Inflammation in Relation to Cognitive Function in an Older Adult Danish Population
Kamer, A. R., Morse, D. E., Holm‐Pedersen, P., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102004 · Cited by 98 · see citing works
The condition of teeth in the UK in 1998 and implications for the future
Nunn, J., MORRIS, J. C., Pine, C. M., Pitts, N. B., Bradnock, G., & Steele, J. G. (2000) · BDJ · doi:10.1038/sj.bdj.4800853 · Cited by 74 · see citing works
Evaluation of patients with Alzheimer's disease before and after dental treatment
Rolim, T. D. S., Fabri, G. M. C., Nitríni, R., et al. (2014) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20140140 · Cited by 70 · see citing works
The clinical evaluation of the oral status in Alzheimer-type dementia patients
Hatipoğlu, M. G., Kabay, S. C., & Güven, G. (2010) · Gerodontology · doi:10.1111/j.1741-2358.2010.00401.x · Cited by 57 · see citing works
Amyloid beta (A4) precursor protein expression in human periodontitis-affected gingival tissues
Kubota, T., Maruyama, S., Abe, D., Tomita, T., Morozumi, T., Nakasone, N., Saku, T., & Yoshie, H. (2014) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2014.03.004 · Cited by 56 · see citing works
Farhad, S. Z., Amini, S., Khalilian, A., Barekatain, M., Mafi, M., Barekatain, M., & Rafei, E. (2014) · Europe PMC (PubMed Central) · Cited by 44 · see citing works
Implications of clinical trial design on sample size requirements
Leon, A. C. (2007) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn035 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Dominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., et al. (2019) · Science Advances · doi:10.1126/sciadv.aau3333 · Cited by 1,966 · see citing works
Sochocka, M., Donskow-Łysoniewska, K., Diniz, B. S., Kurpas, D., Brzozowska, E., & Leszek, J. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1188-4 · Cited by 584 · see citing works
The endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457 · see citing works
The Infectious Etiology of Alzheimer’s Disease
Sochocka, M., Zwolińska, K., & Leszek, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313122937 · Cited by 399 · see citing works
Ilievski, V., Zuchowska, P. K., Green, S. J., Toth, P. T., Ragozzino, M. E., Le, K., Aljewari, H. W., O’Brien-Simpson, N. M., Reynolds, E. C., & Watanabe, K. (2018) · PLOS ONE · doi:10.1371/journal.pone.0204941 · Cited by 372 · see citing works
Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain
Fonseca, M. I., Chu, S.-H., Hernandez, M. X., Fang, M. J., Modarresi, L., Selvan, P., MacGregor, G. R., & Tenner, A. J. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0814-9 · Cited by 337 · see citing works
Peripheral immune system in aging and Alzheimer’s disease
Cao, W., & Zheng, H. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0284-2 · Cited by 214 · see citing works
The Possibility of an Infectious Etiology of Alzheimer Disease
Ashraf, G. M., Tarasov, V. V., Makhmutovа, A., Chubarev, V. N., Avila-Rodriguez, M., Bachurin, S. O., & Aliev, G. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1388-y · Cited by 175 · see citing works
Time to test antibacterial therapy in Alzheimer’s disease
Panza, F., Lozupone, M., Solfrizzi, V., Watling, M., & Imbimbo, B. P. (2019) · Brain · doi:10.1093/brain/awz244 · Cited by 161 · see citing works
Oral Microbiota and Alzheimer’s Disease: Do All Roads Lead to Rome?
Sureda, A., Daglia, M., Argüelles Castilla, S., Sanadgol, N., Fazel Nabavi, S., Khan, H., Belwal, T., Jeandet, P., Marchese, A., Pistollato, F., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2019.104582 · Cited by 143 · see citing works
Infectious agents and Alzheimer's disease
Piekut, T., Hurła, M., Banaszek, N., Szejn, P., Dorszewska, J., Kozubski, W., & Prendecki, M. (2022) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2102073 · Cited by 123 · see citing works
Analysis the Link between Periodontal Diseases and Alzheimer’s Disease: A Systematic Review
Borsa, L., Dubois, M., Sacco, G., & Lupi, L. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18179312 · Cited by 109 · see citing works
Vojtechova, I., Machacek, T., Kristofikova, Z., Stuchlik, A., & Petrasek, T. (2022) · PLOS Pathogens · doi:10.1371/journal.ppat.1010929 · Cited by 92 · see citing works
Modulation of β-Amyloid Fibril Formation in Alzheimer’s Disease by Microglia and Infection
Brown, M. R., Radford, S. E., & Hewitt, E. W. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.609073 · Cited by 67 · see citing works
Yang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63 · see citing works
“The results of an observational cohort study indicated that periodontitis is associated with an increase in cognitive decline in Alzheimer’s disease [120].”
BackgroundAlzheimer disease and the periodontal patient: New insights, connections, and therapies
Ryder, M. I., & Xenoudi, P. (2021) · Periodontology 2000 · doi:10.1111/prd.12389 · Cited by 55 · see citing works
When the infectious environment meets the AD brain
Ganz, T., Fainstein, N., & Ben-Hur, T. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00559-3 · Cited by 39 · see citing works
Chouhan, J. K., Püntener, U., Booth, S. G., & Teeling, J. L. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.760721 · Cited by 24 · see citing works
Self-citationAntibody Engineering for Optimized Immunotherapy in Alzheimer's Disease
Sumner, I. L., Edwards, R. A., Asuni, A. A., & Teeling, J. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00254 · Cited by 24 · see citing works
Self-citationPathogenesis, Animal Models, and Drug Discovery of Alzheimer’s Disease
Xia, Z.-D., Ma, R.-X., Wen, J.-F., Zhai, Y.-F., Wang, Y.-Q., Wang, F.-Y., Liu, D., Zhao, X.-L., Sun, B., Jia, P., et al. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-230326 · Cited by 19 · see citing works
Dumitru, C. N., Dumitru, A. O., Popa, G. V., Marcu, T., Ursu, M., Nechita, A., & Matei, N. M. (2026) · Dentistry Journal · doi:10.3390/dj14050289 · Cited by 6 · see citing works
“GLP-1 receptor agonists (e.g., exenatide, liraglutide, semaglutide), initially developed for type 2 diabetes, have shown neuroprotective effects in animal models by reducing neuroinflammation, oxidative stress, and apoptosis [131–133].”
What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3 · see citing works
- Authors
- 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, V. H., & Holmes, C.
- Affiliations
- Guy's Hospital (GB)
- University of Southampton (GB)
- Moorgreen Hospital (GB)
- Cardiff University (GB)
- Corresponding author
- Holmes, Clive
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-03-10
- Volume
- 11
- Issue
- 3
- Pages
- e0151081
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4786266
- OpenAlex
- W2295588523
- Cited by
- 461
- References
- 29
- Citations by year
- 2026: 30 · 2025: 53 · 2024: 44 · 2023: 60 · 2022: 52 · 2021: 67 · 2020: 54 · 2019: 46 · 2018: 23 · 2017: 26 · 2016: 5 · 2015: 1
- FWCI
- 29.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- GlaxoSmithKline
- Colgate-Palmolive Company
- Dunhill Medical Trust
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Dentistry › Periodontics › Dental Health and Care Utilization
- Keywords
- periodontitis, Alzheimer's disease, cognitive decline, dementia severity, systemic inflammation, inflammatory cytokines, oral hygiene, ADAS-Cog, community-dwelling older adults
- MeSH terms
- Aged, Alzheimer Disease, Cognition Disorders, Female, Follow-Up Studies, Humans, Male, Periodontitis, Time Factors
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
