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

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.