Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods

Wouter A J Vints, Simona Kušleikiene, Samrat Sheoran, Milda Šarkinaite, Kristina Valatkevičiene, Rymante Gleizniene, Mindaugas Kvedaras, Kazimieras Pukenas, Uwe Himmelreich, Vida J Cesnaitiene, Oron Levin, Jeanine Verbunt, Nerijus Masiulis, Wouter A J Vints, Simona Kušleikiene, Samrat Sheoran, Milda Šarkinaite, Kristina Valatkevičiene, Rymante Gleizniene, Mindaugas Kvedaras, Kazimieras Pukenas, Uwe Himmelreich, Vida J Cesnaitiene, Oron Levin, Jeanine Verbunt, Nerijus Masiulis

Abstract

Rationale and objectives: Pro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults.

Materials and methods: Seventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC).

Results: Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults.

Conclusion: Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.

Keywords: aging; brain imaging; cerebral metabolite ratios; cognition; gray matter volume; inflammation; neurochemicals; obesity.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Vints, Kušleikiene, Sheoran, Šarkinaite, Valatkevičiene, Gleizniene, Kvedaras, Pukenas, Himmelreich, Cesnaitiene, Levin, Verbunt and Masiulis.

Figures

Figure 1
Figure 1
(A) Example voxel positions and spectra from a representative subject. (B) Raw (black curve) and fitted (red curve) spectra from LCModel (left hand side panel) and Tarquin (right hand side panel) are illustrated for the left HPC and right DLPFC. Cho, total choline; Cr, creatine + phosphocreatine; DLPFC, dorsolateral prefrontal cortex; DPCC, dorsal posterior cingulate cortex; Glx, glutamate–glutamine complex; HPC, hippocampal cortex; mIns, myoinositol; MTC, medial temporal cortex; NAA, N-acetyl aspartate; SM1, primary sensorimotor cortex.

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