TMAO is associated with higher age, cardiometabolic risk factors and degenerative alterations of the brain in healthy elderly adults.

Trimethylamine N-oxide (TMAO) is a microbiome-based metabolite known to increase with age, cardiovascular and other diseases, with average concentrations mostly higher in males. It was recently found to be associated with neurodegenerative diseases. In this context we aimed to investigate associations between TMAO, cardiometabolic risk factors, cognitive function and brain atrophy in older individuals (67.81 ± 8.86 years of age) with normal neurological status. TMAO was measured by liquid-chromatography tandem mass spectrometry in serum samples from 487 individuals. All participants underwent cognitive testing capturing executive function, motor and memory abilities. In 180 of these individuals, brain MRI was performed to investigate vascular and neurodegenerative changes. In the total cohort higher TMAO concentrations were positively associated with advanced age (p=0.01), BMI (p<0.01), fasting blood sugar (p<0.01), HbA1c (p<0.01) and diabetes (p=0.02). In contrast, we observed negative associations with total cholesterol (p=0.01), LDL (p=0.04) and HDL cholesterol (p=0.04). No significant differences in TMAO concentrations were found between females and males. MRI revealed higher TMAO levels to be associated with lower total grey matter, frontal lobar and hippocampal volume (p=0.01). Summarized, TMAO is associated with higher age, cardiometabolic risk factors and brain atrophy, while there was no difference between the two sexes of this community-dwelling elderly cohort. These findings support that TMAO is mainly a marker of aging processes but also associated with neurodegeneration, even though associations with cognitive functioning were not observed.