Stein-Erik Hafstad Solvang1, Jan Erik Nordrehaug2, Grethe S Tell3, Ottar Nygård4, Adrian McCann5, Per Magne Ueland5, Øivind Midttun5, Klaus Meyer5, Christian A Vedeler6, Dag Aarsland7, Helga Refsum8, A David Smith9, Lasse Melvaer Giil2. 1. Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Institute of Clinical Science, University of Bergen, Norway. Electronic address: steinerik.solvang@gmail.com. 2. Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Institute of Clinical Science, University of Bergen, Norway. 3. Department of Global Public Health and Primary Care, University of Bergen, Norway; Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway. 4. Institute of Clinical Science, University of Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. 5. BevitalA/S, Bergen, Norway. 6. Department of Clinical Medicine, University of Bergen, Norway. 7. Department of Old Age Psychiatry, King's College University, London, UK. 8. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Department of Pharmacology, University of Oxford, UK. 9. Department of Pharmacology, University of Oxford, UK.
Abstract
INTRODUCTION: Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults. METHODS: This cross-sectional study included 2174 participants aged 70-72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner's regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5'phosphate, sex and smoking were considered as potential confounders. RESULTS: Higher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β -0.08, p = 0.001) and COWAT (β -0.08, p = 0.001), but not with DST (β -0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β -0.07; p = 0.001; COWAT: β -0.06, p = 0.010; DST: β -0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition. CONCLUSION: Higher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language.
INTRODUCTION:Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults. METHODS: This cross-sectional study included 2174 participants aged 70-72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner's regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5'phosphate, sex and smoking were considered as potential confounders. RESULTS: Higher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β -0.08, p = 0.001) and COWAT (β -0.08, p = 0.001), but not with DST (β -0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β -0.07; p = 0.001; COWAT: β -0.06, p = 0.010; DST: β -0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition. CONCLUSION: Higher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language.
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