Plasma Ergothioneine Levels and Mushroom Consumption Are Associated with Lower Odds of Cognitive Impairment in Community-Dwelling Older Adults: Findings from the Diet and Healthy Ageing (DaHA) Study

Background: Cognitive impairment poses significant challenges to aging populations globally. Mushrooms, the primary dietary source of ergothioneine (ET), have been associated with cognitive health, but the specific roles of ET and its metabolite S-methyl-ergothioneine (S-ET) remain unclear. Objectives: This study intends to extend previous work on mushroom intake and cognition by simultaneously examining mushroom consumption, plasma ET, and plasma S-ET, and by exploring the independent associations and potential mediation or moderation roles of ET and S-ET in relation to cognitive impairment. Methods: Cross-sectional data from 499 older adults (67 ± 8 years, 75.35% female) from the “Diet and Healthy Ageing Study” (DaHA) in Singapore were analyzed. Cognitive impairment (CI) was defined as Modified Mini-Mental State Examination (MMSE) score < 27. Plasma ET and S-ET concentrations were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Associations were examined using logistic regression, with exploratory mediation and moderation analyses. Results: Mushroom consumption >2 servings/week was associated with lower odds of CI (OR = 0.421, 95% CI: 0.180–0.986). Higher plasma ET levels were also independently associated with lower CI odds. Exploratory moderation analyses suggested that the inverse association between mushroom intake and CI was more evident among individuals with higher ET or S-ET levels (Mushroom × ET interaction: β = −0.008, p = 0.007; Mushroom × S-ET interaction: β = −0.079, p < 0.05). No evidence of exploratory mediation was observed for either ET or S-ET. Conclusions: Higher mushroom intake and plasma ET levels were associated with lower odds of cognitive impairment. Exploratory analyses suggested that the mushroom–cognition association may vary according to ET and S-ET status. The findings on mushroom and ET/S-ET interaction and the lack of a mediating role in our cohort are preliminary and hypothesis-generating and require validation in future longitudinal and intervention studies.