"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."
BUFFALO, NY — August 31, 2026 — A new research paper was published in Volume 18 of Aging on August 11, 2026, titled " TMAO is associated with higher age, cardiometabolic risk factors and degenerative alterations of the brain in healthy elderly adults ."
The study was led by first author Gunter Almer from the Clinical Institute of Medical and Chemical Laboratory Diagnostics at the Medical University of Graz in Austria . The corresponding author is Markus Herrmann from the same institution.
Trimethylamine N-oxide (TMAO) is a metabolite linked to the gut microbiome. Its precursor, trimethylamine (TMA), is produced by gut bacteria from dietary compounds such as L-carnitine and choline and is subsequently converted to TMAO in the liver. Higher circulating TMAO concentrations have previously been associated with cardiovascular and metabolic diseases, but evidence concerning its role in aging and neurodegeneration remains inconsistent.
To investigate these relationships, the researchers measured serum TMAO in 487 neurologically normal, community-dwelling adults from the Austrian Stroke Prevention Study and Austrian Stroke Prevention Family Study. Participants had a mean age of 67.8 years and underwent cognitive testing assessing memory, executive function, and motor abilities. Brain MRI data were also available for 180 participants, allowing the researchers to examine structural and vascular brain changes.
Higher TMAO concentrations were associated with older age and several cardiometabolic risk factors. After adjustment for age, sex, and kidney function, higher TMAO was associated with higher body mass index, fasting blood glucose, HbA1c, and diabetes. Participants aged 70 years or older also had significantly higher TMAO concentrations than younger participants, even after adjustment for kidney function.
The researchers also found inverse associations between TMAO and total, LDL, and HDL cholesterol. The authors note that some of these findings remain difficult to explain and add to inconsistent evidence surrounding TMAO and metabolic health. Because circulating TMAO can increase as kidney function declines, the analyses accounted for estimated glomerular filtration rate, an important potential confounding factor.
The MRI findings provided another important observation. Among the 180 participants with imaging data, higher TMAO concentrations were associated with lower total gray matter, hippocampal, and frontal lobe volumes after adjustment for several clinical factors, including kidney function. The association with hippocampal volume remained significant among participants older than 65 years.
However, these structural associations were not accompanied by measurable differences in cognitive performance. TMAO was not significantly associated with memory, executive function, motor skills, or overall cognitive ability. A correlation between TMAO and neurofilament light chain, a blood marker of neuronal injury, also disappeared after adjustment for age.
"Overall the observed associations are modest and may reflect TMAO as a marker of systemic aging processes rather than a direct mediator of neurodegeneration."
The findings therefore support a cautious interpretation of TMAO's role in aging. Although higher concentrations were associated with cardiometabolic factors and structural indicators of brain atrophy, the study does not establish that TMAO causes these changes. The authors emphasize that previous research has produced conflicting results and that the observed relationships with structural markers of neurodegeneration in the current cohort were relatively weak.
Important limitations include measurement of TMAO at only one time point, the absence of stool samples for microbiome analysis, and the lack of measurements of TMAO precursors such as choline, betaine, L-carnitine, and TMA. Brain MRI data were also available only for the ASPS-Fam subgroup rather than the entire cohort.
Overall, the study links circulating TMAO with older age, cardiometabolic risk factors, and specific measures of brain atrophy in neurologically normal older adults, while finding no corresponding association with cognitive performance. The results suggest that TMAO may be more reflective of systemic aging processes than a direct mediator of neurodegeneration, highlighting the need for further studies examining TMAO metabolism, diet, the gut microbiome, kidney function, and age-related brain changes.
Paper DOI: https://doi.org/10.18632/aging.206401
