Folate and Inflammatory Markers Moderate the Association Between Helicobacter pylori Exposure and Cognitive Function in US Adults Andrew N. Berrett,* Shawn D. Gale,* ,† Lance D. Erickson, ‡ Bruce L. Brown* and Dawson W. Hedges* ,† *Department of Psychology, Brigham Young University, Provo, Utah, † The Neuroscience Center, Brigham Young University, Provo, Utah, ‡ Department of Sociology, Brigham Young University, Provo, Utah Keywords Helicobacter pylori, cognition, inflammation, folate, C-reactive protein, ferritin. Reprint requests to: Andrew N. Berrett, 1001 SWKT, Provo, UT 84602, USA. E-mail: anberre@gmail.com Abstract Background: Helicobacter pylori (H. pylori) infection is associated with cogni- tive deficits in humans, an association potentially mediated or moderated by folate concentration or inflammation. Materials and Methods: We used the National Health and Nutrition Exami- nation Survey (NHANES) datasets to examine whether folate concentration or inflammation mediates or moderates the relationship between H. pylori and cognitive function. Models were performed using linear, Poisson, and zero-inflated Poisson regression, and we performed separate analyses for groups aged 20–59 and 60–90 years with sample sizes ranging from 700 to 1700. Results: We did not find evidence of mediation in either age group. In the 20- to 59-year group, interactions between H. pylori and ferritin (p values ranging from .004 to .039) were associated with worse processing speed, better working memory, and worse reaction time. Interactions between H. pylori and fibrinogen (p values ranging from .023 to .045), C-reactive pro- tein (CRP) (p= .023), and the inflammatory index (p = .045) were associ- ated with worse processing speed. In 60- to 90-year-olds, H. pylori interacted with ferritin and the inflammatory index to predict fewer mathematical errors (p values of .036 and .023). Interactions with folate (p values of .016 and .006) and C-reactive protein (p values ranging from <.001 to .048) were inconsistent in directionality. Conclusions: In this dataset, representative of the US population, inflamma- tion and folate concentrations moderated but did not mediate the association between H. pylori seropositivity and cognition. Helicobacter pylori is a gram-negative bacterium found in the stomach and upper gastrointestinal tract of a signifi- cant portion of the worldwide population [1]. Infection occurs primarily through ingestion but may also occur in utero [2]. Helicobacter pylori locates to less acidic por- tions of the mucosal lining of the gastrointestinal tract ensuring long-term persistence within the host. Gastri- tis typically follows the initial infection and inflamma- tion persists until successful treatment [3]. Genomic studies have described a specific strain of H. pylori that expresses the cagA protein, which can trigger a robust inflammatory response [4]. Beydoun et al. [5] found an association between H. pylori seropositivity and reduced cognitive function- ing in adults. Although Gale et al. [6] did not find sig- nificant main effects between H. pylori and cognitive function in young to middle-aged adults, they did find significant interactions between H. pylori and race-eth- nicity, educational attainment, and latent toxoplasmo- sis that predicted cognitive function after controlling for potential sociodemographic confounds. The associa- tion between H. pylori and cognitive function is consis- tent with similar studies showing an association between other infectious diseases and cognitive func- tioning [7,8]. The mechanism by which H. pylori may affect cognitive function is unclear, although inflammation or changes in folate metabolism could be involved © 2016 John Wiley & Sons Ltd, Helicobacter 1 Helicobacter ISSN 1523-5378 doi: 10.1111/hel.12303