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Blood Metabolite Ergothioneine Linked to Cognition and Alzheimer's Risk in MidlifeBrain Health

Blood Metabolite Ergothioneine Linked to Cognition and Alzheimer's Risk in Midlife

Researchers analyzed nearly 1,000 blood metabolites in over 1,000 middle-aged adults to identify which are linked to brain health. Fourteen metabolites showed replicated associations with cognitive performance across multiple cohorts, and their pattern matched that seen in people who later developed Alzheimer's disease. Ergothioneine — a rare antioxidant found in mushrooms — showed the largest protective effect on cognition. Notably, antacid use was associated with lower ergothioneine levels and worse cognitive scores, with ergothioneine mediating nearly a third of that negative effect. Lifestyle factors, medications, and clinical variables were the dominant drivers of these metabolite levels, collectively explaining up to 29% of the variance. The findings suggest that blood metabolomics at midlife may help identify early Alzheimer's risk windows and that dietary or medication choices could meaningfully shift that risk.

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