TY - JOUR

T1 - Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? A 1H magnetic resonance spectroscopy study at 7 tesla

AU - Lind, Anna

AU - Boraxbekk, Carl Johan

AU - Petersen, Esben Thade

AU - Paulson, Olaf Bjarne

AU - Andersen, Ove

AU - Siebner, Hartwig Roman

AU - Marsman, Anouk

N1 - Publisher Copyright: © 2021 International Society for Neurochemistry

PY - 2021

Y1 - 2021

N2 - Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69–79 years) than younger (18–26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing. (Figure presented.).

AB - Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69–79 years) than younger (18–26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing. (Figure presented.).

KW - C-reactive protein

KW - choline

KW - creatine

KW - interleukin 8

KW - myo-inositol

KW - working memory

U2 - 10.1111/jnc.15456

DO - 10.1111/jnc.15456

M3 - Journal article

C2 - 34142382

AN - SCOPUS:85109864185

VL - 159

SP - 185

EP - 196

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -