Longer Repetition Time Proton MR Spectroscopy Shows Increasing Hippocampal and Parahippocampal Metabolite Concentrations with Aging

J Neuroimaging. 2019 Sep;29(5):592-597. doi: 10.1111/jon.12648. Epub 2019 Jul 4.


Background and purpose: Previous magnetic resonance spectroscopy (MRS) studies have concluded that hippocampal and parahippocampal metabolite concentrations remain stable during healthy adult aging. However, these studies used short repetition times (TR ≤ 2 seconds), which lead to incomplete longitudinal magnetization recovery, and thus, heavily T1 -weighted measurements. It is important to accurately characterize brain metabolites changes with age to enable appropriate interpretations of MRS findings in the context of neurodegenerative diseases. Our goal was to assess hippocampal brain metabolite concentrations in a large cohort of diversely aged healthy volunteers using a longer TR of 4 seconds.

Methods: Left hippocampal MR spectra were collected from 38 healthy volunteers at 3T. Absolute metabolite concentrations were determined for total N-acetyl-aspartate (tNAA), total creatine (tCr), total choline (tCho), glutamate and glutamine (Glx), and myoinositol (mI). Individual partial correlations between each metabolite with age were assessed using demographic information and voxel compartmentation as confounders.

Results: Hippocampal tNAA, tCr, tCho, and mI all increased with age (NAA: R2 = .17, P = .041; tCr: R2 = .45, P = .0002; tCho: R2 = .37, P = .001; mI: R2 = .44, P = .0003). There were no relationships between age and signal to noise ratio, linewidth, or scan date, indicating the correlations were not confounded by spectral quality. Furthermore, we did not observe a trend with age in the voxel tissue compartmentations.

Conclusions: We observed increases in hippocampal/parahippocampal metabolite concentrations with age, a finding that is in contrast to previous literature. Our findings illustrate the importance of using a sufficiently long TR in MRS to avoid T1 -relaxation effects influencing the measurement of absolute metabolite concentrations.

Keywords: N-acetyl-aspartate; T1-weighting; aging; hippocampus; magnetic resonance spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aging / metabolism*
  • Aspartic Acid / analogs & derivatives
  • Choline / metabolism
  • Creatine / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism*
  • Humans
  • Inositol / metabolism
  • Male
  • Middle Aged
  • Parahippocampal Gyrus / diagnostic imaging
  • Parahippocampal Gyrus / metabolism*
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Protons
  • Young Adult


  • Protons
  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • Inositol
  • Creatine
  • Choline