Ergothioneine is a well-known antioxidant that is abundant in both human red blood cells and in fission yeast responding to nutritional stress. In frail elderly people, whose ageing organs undergo functional decline, there is a correlation between ergothioneine levels and cognitive, but not skeletal muscle decline. In patients suffering from dementia, including Alzheimer's disease with hippocampal atrophy, deteriorating cognitive ability is correlated with declining ergothioneine levels. S-methyl-ergothioneine, trimethyl-histidine and three other trimethyl-ammonium compounds also decrease sharply in dementia, whereas compounds such as indoxyl-sulfate and quinolinic acid increase, possibly exacerbating the disease. Using these opposing dementia markers, not only diagnosis, but also therapeutic interventions to mitigate cognitive decline may now become possible.