Clinical and Bacterial Markers of Periodontitis and Their Association with Incident All-Cause and Alzheimer’s Disease Dementia in a Large National Survey
Open accessAbstract
Microbial agents including periodontal pathogens have recently appeared as important actors in Alzheimer's disease (AD) pathology. We examined associations of clinical periodontal and bacterial parameters with incident all-cause and AD dementia as well as AD mortality among US middle-aged and older adults. Clinical [Attachment Loss (AL); probing pocket depth (PPD)] and bacterial [pathogen immunoglobulin G (IgG)] periodontal markers were investigated in relation to AD and all-cause dementia incidence and to AD mortality, using data from the third National Health and Nutrition Examination Surveys (NHANES III, 1988-1994) linked longitudinally with National Death Index and Medicare data through January 1, 2014, with up to 26 years of follow-up. Sex- and age-specific multivariable-adjusted Cox proportional hazards models were conducted. Among those ≥65 years, AD incidence and mortality were consistently associated with PPD, two factors and one cluster comprised of IgG titers against Porphyromonas gingivalis (P. gingivalis), Prevotella melaninogenica (P. melaninogenica) and Campylobacter rectus (C. rectus) among others. Specifically, AD incidence was linked to a composite of C. rectus and P. gingivalis titers (per SD, aHR = 1.22; 95% CI, 1.04-1.43, p = 0.012), while AD mortality risk was increased with another composite (per SD, aHR = 1.46; 95% CI, 1.09-1.96, p = 0.017) loading highly on IgG for P. gingivalis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, C. rectus, Streptococcus intermedius, Capnocylophaga Ochracea, and P. melaninogenica. This study provides evidence for an association between periodontal pathogens and AD, which was stronger for older adults. Effectiveness of periodontal pathogen treatment on reducing sequelae of neurodegeneration should be tested in randomized controlled trials.
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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 [74]
The Results (page not supplied) report that higher P. gingivalis IgG titers were associated with increased incident AD dementia risk, particularly among women. This contradicts the claim that the titers have not been related to AD risk. The cited passages do not report MMSE or ADAS-cog performance or mucosal copy numbers. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredA US study found that in 3521 people aged ≥65 years different periodontal diseases were associated with either all cause dementia or AD or AD death over 26 years of follow-up.
“A US study controlling for demographic, vascular health and SES, found that in 3521 people aged ≥ 65 years different (but not the same) periodontal disease were associated with either all cause dementia or AD or AD death over 26 years of follow-up.(368)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [368]
The Discussion reports that different periodontal markers were linked with at least one of incident all-cause dementia, incident AD, and AD mortality among older adults. The Methods describe adjustment for demographic, socioeconomic, and health-related factors, with analyses stratified at age ≥65. However, the Study Sample section describes participants aged ≥45 and varying sample sizes; it does not substantiate 3,521 participants all aged ≥65. Follow-up ran through January 2014 from a 1988–1994 survey baseline, so 26 years is a possible maximum, not a duration established for every participant. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMucosa 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 [74]
The Results section on pathogen factors links a composite that includes F. nucleatum IgG titers to increased AD mortality risk in adults aged 65 or older. It does not report mucosal F. nucleatum copy numbers or establish an individual F. nucleatum association with AD incidence. The Methods describe serum IgG measurements for A. naeslundii, but the passages found do not link lower titers to AD. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAlthough 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 [74]
The Results section reports that C. rectus IgG titers were associated with increased all-cause dementia risk. It reports only a marginal association among women for a multi-pathogen cluster containing T. denticola, not an individual T. denticola titer association. The Methods describe serum IgG measurements, not mucosal copy numbers, so the claimed lack of association between copy numbers and AD risk is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMucosa 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 [74]
The Methods (Periodontal pathogens; page not provided) show that this study measured serum IgG titers, not mucosal bacterial copy numbers. The Results (Periodontal pathogen factor and clusters; page not provided) report a marginal association with AD and all-cause dementia among women for a cluster containing both named bacteria. That does not establish an association for either bacterium individually, but it does not support the claim’s unqualified statement that their titers have not been associated with these risks. (LLM, conf=0.84)
Experimental — accuracy not yet measured
The dental disease group had had less education, lower disposable income, and more comorbidities.
“The dental disease group had had less education, lower disposable income, and more comorbidities.”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [368]
The Results section (‘Participant characteristics by age group and sex’; page unavailable) links age with periodontal measures and comorbidity, but does not compare a dental-disease group with a non-disease group on education, disposable income, or comorbidities. Searches for those terms and for periodontitis-related socioeconomic differences found no such comparison in our copy. (LLM, conf=0.70)
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Oral Microbiota Profile of Individuals Who Abuse Methamphetamine
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- Authors
- Beydoun, M. A., Beydoun, H. A., Hossain, S., El-Hajj, Z. W., Weiss, J., & Zonderman, A. B.
- Affiliations
- National Institutes of Health (US)
- Alexander T. Augusta Military Medical Center (US)
- Department of Biology, McGill University, Montreal, QC, Canada
- Leonard Davis Institute of Health Economics (US)
- Corresponding author
- Beydoun, May A.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2020-05-05
- Volume
- 75
- Issue
- 1
- Pages
- 157-172
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC11008556
- OpenAlex
- W3015489480
- Cited by
- 201
- References
- 43
- Citations by year
- 2026: 36 · 2025: 38 · 2024: 32 · 2023: 31 · 2022: 31 · 2021: 28 · 2020: 5
- FWCI
- 24.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 AG999999, Z01-AG000513)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- periodontitis, Alzheimer's disease
- MeSH terms
- Aged, Alzheimer Disease, Prevotella melaninogenica, Dementia, Female, Health Surveys, Humans, Male, Middle Aged, Periodontitis, United States, Incidence, Porphyromonas gingivalis, Campylobacter rectus
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