# Higher Plasma Kynurenine to Tryptophan Correlates with an Increased Incidence of Mild Cognitive Impairment in Treated Metabolic Syndrome Patients

## TL;DR

Higher kynurenine to tryptophan ratio in plasma is linked to increased risk of mild cognitive impairment in patients with treated metabolic syndrome.

## Contribution

Validated metabolite data and identification of KTR as a potential MCI risk marker in treated MetS patients.

## Key findings

- MCI was positively associated with the kynurenine-to-tryptophan ratio (KTR) after adjusting for age, gender, and BMI.
- A one-unit increase in KTR increased the probability of developing MCI by 371%.
- Validated metabolite data can support future research and machine learning models for biomarker discovery.

## Abstract

An increase in cognitive impairment
was observed in metabolic syndrome (MetS) patients. Although alterations
in metabolomic profiles have been identified as potential plasma/serum
biomarkers of mild cognitive impairment (MCI) and MetS, findings remain
inconsistentprobably due to the heterogeneity among MetS patients
and the lack of subsequent validation using targeted analysis after
the initial untargeted analysis. In this study, we validated mass
spectrometry-based quantitation methods and quantified amino acids,
fatty acids, and tryptophan metabolites in the kynurenine pathway
in the plasma of 95 treated MetS patients with and without MCI assessed
by the Montreal Cognitive Assessment. We found that MCI was positively
associated with the kynurenine-to-tryptophan ratio (KTR) after the
adjustment for age, gender, and BMI, as well as negatively associated
with C20:3 [all-Z-8,11,14] and lysine. A one-unit increase in KTR
resulted in an increased probability of developing MCI by 371%. In
contrast, one-unit increases in C20:3 and lysine were associated with
decreased odds of developing MCI by 81 and 78%, respectively. Our
finding underscores prominent neuroinflammation, beyond normal aging,
in MetS patients, even under ongoing clinical treatment. It also points
to the potential of KTR as a risk marker for MCI, offering a valuable
complement to the existing cognitive assessments that may be influenced
by the educational background. In addition, the validated metabolite
data serve as an invaluable resource for future research. They can
facilitate comparisons across different studies, contribute to large-scale
analyses, and be used in machine learning models for discovering and
validating new biomarkers.