Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging

Abstract

Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

Keywords: Choline (Cho); Glutamate (Glu); Glutamine (Gln); Myo-inositol (mI); N-acetyl-aspartate (NAA); Neuronal metabolic activity; Normal aging; Total creatine (tCr); Whole-brain MR spectroscopic imaging.

Figure 1

Example individual images of NAA, Cho, tCr, Glx, and mI and the corresponding T1-weighted images (T1w) at two axial sections around the level of centrum semiovale obtained from a female of 25 years old (Fig.1A) and a female of 70 years old (Fig.1B), and two single voxel spectra obtained from the younger subject in occipital gray matter and parietal white matter (Fig. 1C). Hyperintensitive areas due to excessive linewidth were excluded in the lobar calculations.

Figure 2

Cerebral lobar NAA concentrations and fractional tissue volumes of gray matter, white matter, and CSF plotted as functions of age, including linear fits with 95% prediction interval and 95% confidence interval (only for NAA) for statistically significant cases (p < 0.01).

Figure 3

Frontal lobar [NAA] in native brain tissue (Fig.3A) and GM (Fig. 3B) plotted against age and FVGM showing the correlations between these variables.