Blood metabolome links midlife brain health to genes, gut microbiome, and exposures

In 1,082 dementia-free midlife participants, researchers linked 14 cognition-associated blood metabolites (ergothioneine strongest) and 22 metabolites with MRI brain markers. The metabolite patterns mirrored the signature of incident AD across replication cohorts. Genetic variation, gut microbiota, lifestyle, clinical factors, and medications all shaped metabolite levels, with lifestyle and clinical factors being particularly influential; antacid use correlated with worse cognition and lower ergothioneine, which mediated about 31.5% of this effect. The cognition and AD-risk metabolite signatures overlap, suggesting prevention avenues via modifiable exposures and gut microbiome factors.