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Helicobacter pylori, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer’s disease dementia in a large national survey

Molecular Psychiatry volume 26, pages 6038–6053 (2021)Cite this article

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Abstract

Co-infection between Helicobacter pylori (Hp) and groups of periodontal pathogens may alter the onset of Alzheimer’s disease (AD) and all-cause dementia. We examined the interactive associations among Hp sero-positivity, periodontal disease (Pd), and infections with incident AD and all-cause dementia, among older adults (≥65 years at baseline). Up to 1431 participants from phase 1 of the National Health and Nutrition Survey III (1988–1991) had complete data till January 1st, 2014 on Hp sero-positivity with a mean follow-up of 10–11 years for AD and all-cause dementia incidence. Exposures consisted of 19 periodontal pathogens, constructed factors and clusters, and two Pd markers- probing depth and clinical attachment loss (CAL). Cox proportional hazards models were performed. Around 55% of the selected sample was Hp+. We found that Prevotella intermedia, Campylobacter Rectus, Factor 2 (Pi/Prevotella nigrescens/Prevotella melaninogenica), and the Orange-Red cluster interacted synergistically with Hp sero-positivity, particularly with respect to AD incidence. The presence of higher levels of Actinomyces Naeslundii (An) enhanced the effect of being Hp+ on both AD and all-cause dementia incidence. In contrast, Fusobacterim nucleatum (Fn), and Factor 1 (which included Fn), exhibited an antagonistic interaction with Hp in relation to all-cause dementia. Both probing depth and CAL had direct associations with all-cause dementia among Hp+ individuals, despite nonsignificant interaction. Selected periodontal pathogen titers, factors, and clusters interacted mostly synergistically, with Hp sero-positivity, to alter the risk of AD and all-cause dementia. Ultimately, a randomized controlled trial is needed, examining effects of co-eradication of Hp and select periodontal pathogens on neurodegenerative disease.

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Acknowledgements

The authors would like to thank Mr. Negasi Beyene (CDC/NCHS/RDC) and Mr. Ray Kuntz (AHRQ) for their help with access to the restricted data at the RDC and facilitating data analysis at the AHRQ headquarters, Rockville, MD. We would also like to thank Ms. Megan Williams and Ms. Nicolle Mode (NIA/NIH/IRP) for internally reviewing our manuscript.

Funding

This study was entirely supported by the National Institute on Aging, Intramural Research Program (NIA/NIH/IRP).

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Authors and Affiliations

  1. Laboratory of Epidemiology and Population Sciences, National Institutes on Aging, NIA/NIH/IRP, Baltimore, MD, USA

    May A. Beydoun, Sharmin Hossain & Alan B. Zonderman

  2. Fort Belvoir Community Hospital, Fort Belvoir, VA, USA

    Hind A. Beydoun

  3. Population Studies Center and the Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA

    Jordan Weiss

  4. McGill University, Montreal, QC, Canada

    Ziad W. El-Hajj

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  1. May A. Beydoun
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Contributions

MAB: Study concept, plan of analysis, data management, statistical analysis, literature search, write-up of the manuscript, revision of the manuscript. HAB: Plan of analysis, literature search and review, write-up of parts of the manuscript, revision of the manuscript. JW: Assistance with statistical analysis, write-up of parts of the manuscript, revision of the manuscript. SH: Plan of analysis, literature search and review, write-up of parts of the manuscript, revision of the manuscript. ZE-H: Literature search and review, write-up of parts of the manuscript, revision of the manuscript. ABZ: Study concept, plan of analysis, write-up of parts of the manuscript, revision of the manuscript.

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Correspondence to May A. Beydoun.

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Beydoun, M.A., Beydoun, H.A., Weiss, J. et al. Helicobacter pylori, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer’s disease dementia in a large national survey. Mol Psychiatry 26, 6038–6053 (2021). https://doi.org/10.1038/s41380-020-0736-2

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