Age related changes in metabolite concentrations in the normal spinal cord.

Khaled Abdel-Aziz,Olga Ciccarelli,Claudia A M Wheeler-Kingshott,Alan J Thompson,Daniel R Altmann,Bhavana S Solanky,Marios C Yiannakas

doi:10.1371/journal.pone.0105774

Abstract

Magnetic resonance spectroscopy (MRS) studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23–65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010) and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002) was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging.

Highlights

Human senescence is associated with deterioration in physical performance which, in part, can be attributed to age-related neurodegeneration of the spinal cord
We used a single voxel Magnetic resonance spectroscopy (MRS) protocol optimised for improved signal-to-noise ratio (SNR) to permit quantification of Glx from the spinal cord [37]
A higher SNR was achieved by employing a longer voxel and increased signal averaging compared to earlier MRS protocols [29,30,45,46]

Summary

Introduction

Human senescence is associated with deterioration in physical performance which, in part, can be attributed to age-related neurodegeneration of the spinal cord. Quantitative morphometric studies in humans show that the decrease in dorsal root fibres begins in the third decade of life [14], whilst quantitative MRI has shown that diffusion anisotropy in the upper cervical cord declines with normal aging, with loss of fibre coherence beginning from the age of ten [15]. Conventional MRI of the spinal cord lacks the necessary sensitivity to detect these microstructural changes. The development of new quantitative MRI techniques, which are more sensitive to change in underlying tissue microstructure and metabolism, may be much more suited to studying aging of the spinal cord in vivo [22]

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