The role of the kynurenine pathway in cognitive functioning after stroke: A prospective clinical study.

Abstract

BACKGROUND:

The kynurenine pathway is the main metabolic pathway of tryptophan degradation and has been associated with stroke and impaired cognitive functioning, but studies on its role in post-stroke cognitive impairment (PSCI) are scarce. We aimed to investigate associations between metabolites of the kynurenine pathway at baseline and post-stroke cognitive functioning over time.

METHODS:

Baseline plasma kynurenines were quantified in 198 stroke patients aged 65.4 ± 10.8 years, 138 (69.7%) men, who were followed up over a period of three years after stroke. Baseline and longitudinal associations of kynurenines with PSCI and cognitive domain scores were investigated using linear mixed models, adjusted for several confounders.

RESULTS:

No evidence of associations between kynurenines and odds of PSCI were found. However, considering individual cognitive domains, higher plasma levels of anthranilic acid (AA) were associated with better episodic memory at baseline (β per SD 0.16 [0.05, 0.28]). Additionally, a linear-quadratic association was found for the kynurenic acid/ quinolinic acid ratio (KA/QA), a neuroprotective index, with episodic memory (Wald χ2 = 8.27, p = .016). Higher levels of KA were associated with better processing speed in women only (pinteraction = .008; β per SD 0.15 [95% CI 0.02, 0.27]). These associations did not change over time.

CONCLUSIONS:

Higher levels of KA, AA and KA/QA were associated with better scores on some cognitive domains at baseline. These associations did not change over time. Given the exploratory nature and heterogeneity of findings, these results should be interpreted with caution, and verified in other prospective studies.

• Authors: Lieke Bakker, Inez H G B Ramakers, Simone J P M Eussen, Kyonghwan Choe, Daniel L A van den Hove, Gunter Kenis, Bart P F Rutten, Robert J van Oostenbrugge, Julie Staals, Arve Ulvik, Per M Ueland, Frans R J Verhey, Sebastian Köhler
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 454 Pg. 120819 (11 15 2023) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 37852105 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Kynurenine
• Biomarkers
• anthranilic acid
• Kynurenic Acid

Topics

• Male
• Humans
• Female
• Kynurenine (metabolism)
• Prospective Studies
• Biomarkers
• Stroke (complications)
• Kynurenic Acid
• Cognition