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bioRxiv · 10.1101/2022.06.08.495050

Neurometabolic timecourse of healthy aging

Gong, T.·Hui, S. C. N.·Zollner, H. J.·Britton, M.·Song, Y.·Chen, Y.·Gudmundson, A. T.·Hupfeld, K. E.·Murali-Manohar, S.·Porges, E.·Oeltzschner, G.·Chen, W.·Wang, G.·Edden, R. A. E.
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Abstract

PurposeThe neurometabolic timecourse of healthy aging is not well-established, in part due to diversity of quantification methodology. In this study, a large structured cross-sectional cohort of male and female subjects throughout adulthood was recruited to investigate neurometabolic changes as a function of age, using consensus-recommended magnetic resonance spectroscopy quantification methods. Methods102 healthy volunteers, with approximately equal numbers of male and female participants in each decade of age from the 20s, 30s, 40s, 50s, and 60s, were recruited with IRB approval. MR spectroscopic data were acquired on a 3T MRI scanner. Metabolite spectra were acquired using PRESS localization (TE = 30 ms; 96 transients) in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Water-suppressed spectra were modeled using the Osprey algorithm, employing a basis set of 18 simulated metabolite basis functions and a cohort-mean measured macromolecular spectrum. Pearson correlations were conducted to assess relationships between metabolite concentrations and age for each voxel; paired t-tests were run to determine whether metabolite concentrations differed between the PCC and CSO. ResultsTwo datasets were excluded (1 ethanol; 1 unacceptably large lipid signal). Statistically significant age-by-metabolite correlations were seen for tCr (R2=0.36; p<0.001), tCho (R2=0.11; p<0.001), sI (R2=0.11; p=0.004), and mI (R2=0.10; p<0.001) in the CSO, and tCr (R2=0.15; p<0.001), tCho (R2=0.11; p<0.001), and GABA (R2=0.11; p=0.003) in the PCC. No significant correlations were seen between tNAA, NAA, GSH, Glx or Glu and age in either region (all p>0.25). Levels of sI were significantly higher in the PCC in female subjects (p<0.001) than in male subjects. There was a significant positive correlation between linewidth and age. ConclusionThe results indicated age correlations for tCho, tCr, sI, and mI in CSO and for tCr, tCho and GABA in PCC, while no age-related changes were found for NAA, tNAA, GSH, Glu or Glx. Our results provide a normative foundation for future work investigating the neurometabolic time course of healthy aging using MRS. HighlightsO_LIA large structured cross-sectional cohort of neurometabolic aging dataset is presented; C_LIO_LIAge correlations were observed for tCho, tCr, sI, and mI in CSO and for tCr, tCho and GABA in PCC; C_LIO_LINo age correlations were found for NAA, tNAA, GSH, Glu or Glx in either region. C_LI

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Gong, T., Hui, S. C. N., Zollner, H. J., Britton, M., Song, Y., Chen, Y., Gudmundson, A. T., Hupfeld, K. E., Murali-Manohar, S., Porges, E., Oeltzschner, G., Chen, W., Wang, G., Edden, R. A. E.. 2022-06-10. Neurometabolic timecourse of healthy aging. https://doi.org/10.1101/2022.06.08.495050

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