1041 Sleep, but Not Proton Pump Inhibitor Use, Mediates Reflux-Related Memory Decline: Evidence from the EPISONO Study

Abstract Introduction Previous research has suggested that prolonged proton pump inhibitor (PPI) use to treat reflux symptoms may be associated with a higher risk of dementia, potentially through disruptions in homocysteine (Hcy) metabolism, although the evidence remains inconclusive. This study aimed to investigate the relationships between self-reported laryngopharyngeal reflux (LPR) symptoms, PPI use, sleep quality, and memory outcomes, and to evaluate whether sleep disturbances or circulating Hcy levels mediate these associations in a population-based sample. Methods Data from participants of the EPISONO 2018 study were analyzed, including individuals with and without LPR symptoms. Memory performance was assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ). Sleep quality and insomnia severity were evaluated with the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). Plasma concentrations of cobalamin, folate, and Hcy were measured. Mediation analyses were conducted to determine whether sleep disturbances or variations in the Hcy metabolic pathway contributed to the associations between LPR symptoms and memory outcomes. Results LPR symptoms were linked to poorer memory performance, with indirect effects partially mediated by sleep quality (7.3%) and insomnia (18.7%). No mediating role of Hcy was identified. Individuals reporting LPR symptoms without PPI use demonstrated worse PRMQ scores, and participants with LPR, regardless of PPI use, showed poorer PSQI scores. Elevated ISI scores were observed in both the LPR/no-PPI use group and the no-LPR/PPI use group. Conclusion Self-reported LPR symptoms are associated with diminished memory performance, and this relationship is partly explained by sleep disturbances. These findings highlight the importance of assessing and addressing sleep problems in individuals presenting with LPR. Support (if any) This study was supported by the Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo, Brazil. MLA, ST and VDA are recipients of CNPq fellowships. MLA and VDA receive grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (#2020/13467-8 and #23/08657-0, respectively).