Altered macromolecular pattern and content in the aging human brain

Abstract

The resonances originating from proteins underlie those of metabolites in brain ¹H NMR spectra. These resonances have different physical properties from those of metabolites such as shorter T ₁ and T ₂ relaxation time constants. The age dependence of macromolecular pattern and content in the human brain were investigated with a focus on adults over 66 years old using ultra-high field in vivo magnetic resonance spectroscopy. Eighteen young and twenty three cognitively normal older adults were studied at 7 T. Metabolite spectra were acquired in the occipital cortex and the posterior cingulate cortex with single voxel STEAM spectroscopy in fourteen young and twenty older adults. Macromolecular spectra were acquired in the occipital cortex using an inversion-recovery STEAM sequence in four young and three older adults. The macromolecular pattern was apparent over the 0.5 to 4.5 ppm range in the inversion-recovery spectra and over the 0.5 to 2 ppm range in the metabolite spectra. Macromolecular content was quantified from metabolite spectra using LCModel and from inversion-recovery spectra using integration. Age-associated differences in the macromolecular pattern were apparent via both types of spectra, with the largest difference observed for the 1.7 and 2 ppm macromolecular resonances. A higher macromolecular content was observed in the older adults for both brain regions. Age-specific macromolecular spectra are needed when comparing metabolite spectra from subjects of differing ages because of age-associated differences in macromolecular pattern. Age-associated pattern and content differences may provide information about the aging process.

Graphical abstract

Age-associated differences in the macromolecular patterns were apparent in STEAM spectra without and with inversion-recovery metabolite nulling, with the largest differences observed for the 1.7 and 2 ppm macromolecular resonances. A higher macromolecular content was observed in the older adults in two brain regions studied, the occipital cortex and the posterior cingulate cortex. Age-specific macromolecular spectra are needed when comparing metabolite spectra from subjects of differing ages. Age-associated pattern and content differences may provide information about the aging process.