Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study.

AIM: To investigate the association between serum ergothioneine and risk of developing dementia and its subtypes in a community-dwelling older population. METHODS: In this prospective longitudinal analysis of participants enrolled in the Hisayama Study, 1344 Japanese community-residents aged 65 years and over without dementia at baseline were followed prospectively for a median of 11.2 years (2012-2023). Serum ergothioneine levels were quantified using liquid chromatography-mass spectrometry and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals for the association between serum ergothioneine levels and the risk of dementia subtypes. RESULTS: During the follow-up, 273 participants developed all-cause dementia. Among them, 201 had Alzheimer's disease (AD) and 72 had non-Alzheimer's disease (non-AD) dementia. The age- and sex-adjusted HRs for all-cause dementia, AD, and non-AD dementia decreased progressively across increasing quartiles of serum ergothioneine (all P for trend <0.05). These associations remained significant after adjustment for a wide range of cardiovascular, lifestyle, and dietary factors, including daily vegetable intake (P for trend <0.05). In subgroup analyses stratified by daily vegetable intake, higher serum ergothioneine levels were consistently associated with lower dementia risk, irrespective of vegetable consumption. CONCLUSIONS: Our findings showed that higher serum ergothioneine levels were associated with a lower risk of developing all-cause dementia, AD, and non-AD dementia in an older Japanese population. Since ergothioneine cannot be synthesized in the human body, a diet rich in ergothioneine may be beneficial in reducing the risk of dementia.