TY - JOUR
T1 - The role of the kynurenine pathway in cognitive functioning after stroke
T2 - A prospective clinical study
AU - Bakker, Lieke
AU - Ramakers, Inez H G B
AU - J P M Eussen, Simone
AU - Choe, Kyonghwan
AU - van den Hove, Daniel L A
AU - Kenis, Gunter
AU - Rutten, Bart P F
AU - van Oostenbrugge, Robert J
AU - Staals, Julie
AU - Ulvik, Arve
AU - Ueland, Per M
AU - Verhey, Frans R J
AU - Köhler, Sebastian
PY - 2023/11/15
Y1 - 2023/11/15
N2 - 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 (ß 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 ? = 8.27, p = .016). Higher levels of KA were associated with better processing speed in women only (p = .008; ß 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.
AB - 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 (ß 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 ? = 8.27, p = .016). Higher levels of KA were associated with better processing speed in women only (p = .008; ß 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.
KW - Cognition
KW - Kynurenine pathway
KW - Kynurenines
KW - Plasma
KW - Post-stroke cognitive impairment
KW - Stroke
U2 - 10.1016/j.jns.2023.120819
DO - 10.1016/j.jns.2023.120819
M3 - Article
SN - 1878-5883
VL - 454
JO - Journal of the neurological sciences
JF - Journal of the neurological sciences
IS - 1
M1 - 120819
ER -