Longitudinal Association of Inflammatory Diets on Cognition in Older Adults: Insights from the Oral-Gut-Brain Axis

The oral-gut-brain axis is known to influence dementia development, but the interactions between an inflammatory diet, inflammatory conditions such as periodontitis and Helicobacter pylori (Hp) infection, and their effects on cognitive function remain unclear. This study aims to investigate how periodontitis and Hp infection affect the association between an inflammatory diet and cognitive performance.

This prospective cohort study was conducted from 2011 to 2019, involving community-dwelling older adults (≥ 65 years old) without dementia, recruited between 2011 and 2013 (N = 511). At baseline, dietary inflammatory potential was assessed by the Empirical Dietary Inflammatory Index (EDII) using a 44-item semi-quantitative food frequency questionnaire. Periodontal status was evaluated by a dentist, and Hp immunoglobulin G levels were measured. Global and domain-specific cognitive functions were assessed at baseline and during three biennial follow-ups. A generalized linear mixed model was used to examine the association between the EDII and cognitive function, adjusting for important covariates. Stratified analyses were further conducted by periodontal status and Hp seropositivity, respectively.

One unit increase in the EDII, indicating a more pro-inflammatory diet, was associated with poor memory performance (Logical Memory-immediate free recall: $\hat{\beta }$  = -0.61, 95% confidence interval (CI) = -1.02 to -0.21; delayed free recall: $\hat{\beta }$  = -0.64, 95% CI = -1.06 to -0.22). This association was more pronounced among participants with periodontitis and Hp seropositivity ( $\hat{\beta }$  = -1.15 to -0.82). Significant interactions were found between the EDII and periodontitis in the memory domain (p _interaction = 0.01).

The association between an inflammatory diet and memory may be more pronounced in older adults with periodontitis and Hp seropositivity. These findings support the relevance of healthy eating, oral health maintenance, and Hp management in maintaining cognitive health.