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. 2014 Oct 13;9(10):e105774.
doi: 10.1371/journal.pone.0105774. eCollection 2014.

Age related changes in metabolite concentrations in the normal spinal cord

Khaled Abdel-Aziz  1 , Bhavana S Solanky  2 , Marios C Yiannakas  2 , Daniel R Altmann  3 , Claudia A M Wheeler-Kingshott  2 , Alan J Thompson  4 , Olga Ciccarelli  4
Affiliations

Age related changes in metabolite concentrations in the normal spinal cord

Khaled Abdel-Aziz et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: OC receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the Department of Health Comprehensive Biomedical Centre, the International Spinal Cord Research Trust (ISRT) and the Engineering and Physical Sciences Research Council (EPSRC); she has received honoraria from Bayer Schering and GE. AT has received honoraria for consultancy from Eisai Ltd, BTG International, Novartis; honoraria and support for travel for lecturing from Serono Symposia International Foundation and Novartis; support for travel for consultancy from MSIF; and honorarium from Sage for editorship of Multiple Sclerosis Journal. BS receives funding from Philips medical. CAMW is on the advisory board for BG12 (Biogen) and receives grants (PI and co-applicant) from ISRT, EPSRC, Wings of Life, MS Society, Biogen Idec and Novartis. The other authors have nothing to declare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Planning of spectroscopy scans.
Coronal (a) and sagittal (b) T2-weighted images of the upper cervical cord in a healthy subject showing voxel placement The NAA voxel (orange) is centred on the C2/3 intervertabral disc, avoiding surrounding CSF. The white voxel illustrates the chemical shift displacement of water. Keeping both the orange voxel (on resonance, 2.02 ppm) and white voxel (4.7 ppm) within the cord, ensures that metabolites between 2.02 and 4.7 ppm (tNAA, tCr, tCho, Glx, Ins) also arise from within the spinal cord and chemical shift displacement of each metabolite need not be an issue. Positioning of the rostrocaudal OVS slabs is shown in periphery of images a+b and positioning of the anterior-posterior OVS slabs is shown in c.
Figure 2
Figure 2. Representative spectra obtained using LCModel from 3 study participants.
Figure 3
Figure 3. Scatter plots of relationship between age and (A) tNAA, (B) Glx, (C) tCho, (D) Ins and (E) Cr concentrations from the upper cervical cord.
Regression lines are shown where there was a significant association (A, B). No significant association was seen between age and tCho, Ins or Cr (C–E).
See this image and copyright information in PMC

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