Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age

Abstract

Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.

Indoleamine 2,3‐Dioxygenase‐Dependent Neurotoxic Kynurenine Metabolism Contributes to Poststroke Depression Induced in Mice by Ischemic Stroke along with Spatial Restraint Stress

“…Basically, IDO1 is the initial enzyme that converts tryptophan to kynurenine which may lead to the production of neuroactive metabolites such as kynurenic acid (KA), 3-hydroxykynurenine (3-HK), and QUIN [26]. Recently, it has been reported that the kynurenine pathway becomes more active with age and the 3-HK level is positively associated with depression in nondemented women over 50 years of age [27].…”

Serum Kynurenines Correlate With Depressive Symptoms and Disability in Poststroke Patients: A Cross-sectional Study

“…Tryptophan (Trp), L-kynurenine (L-Kyn), and KYNA levels were measured by an HPLC (high-performance liquid chromatography) method with fluorescence detection. 18 Briefly, 20 μL of serum supernatant sample were injected onto an Eclipse XDB-C18 reverse phase column (5-μm, 4.6 × 150 mm), and isocratically eluted with a mobile phase consisting of 50 mM sodium acetate, 250 mM of zinc acetate, and 3% of acetonitrile, pH adjusted to 6.2 with glacial acetic acid, at a flow rate of 1 mL/min; L-Kyn was eluted with the same mobile phase but without acetonitrile. KYNA was detected at excitation wavelength: 344 nm, emission wavelength: 398 nm, and L-Kyn at excitation wavelength: 368 nm, emission wavelength: 480 nm.…”

“…The 3HK levels were determined using an electrochemical method. 18 Briefly, 40 μL of sample were injected onto a Adsorbosphere Catecholamine C18 reverse phase column (3 μm, 4.6 mm × 100 mm) and eluted at a constant flow rate of 0.6 mL/min with a mobile phase containing 9% of triethylamine, 0.59% phosphoric acid, 0.27 mM ethylenediaminetetraacetic acid (EDTA), and 8.9 mM heptane sulfonic acid. The retention time was ~11 minutes.…”

Galantamine-Memantine Combination and Kynurenine Pathway Enzyme Inhibitors in the Treatment of Neuropsychiatric Disorders

“…Apart from animal studies, data derived from human populations have also revealed a significant correlation between elevated serum KYN/L-TRP ratio (indicative of inflammation-driven KP induction) and a progressively poor cognitive function [69,70]. A possible association between aging and raised KYN/L-TRP ratio, accompanied by a poor mental capacity, was first hinted by Ramos-Chávez et al [71]. Besides KYN/L-TRP, a progressively rising KYNA/QUIN ratio has also been strongly linked with a poor cognitive performance in cases of schizophrenia.…”