Age-Related Differences in White Matter Integrity in Healthy Human Brain: Evidence from Structural MRI and Diffusion Tensor Imaging

Abstract

The aim is to investigate the relationship between microstructural white matter (WM) diffusivity indices and macrostructural WM volume (WMV) among healthy individuals (20-85 years). Whole-brain diffusion measures were calculated from diffusion tensor imaging using FMRIB software library while WMV was estimated through voxel-based morphometry, and voxel-based analysis was carried out using tract-based spatial statistics. Our results revealed that mean diffusivity, axial diffusivity, and radial diffusivity had shown good correlation with WMV but not for fractional anisotropy (FA). Voxel-wise tract-based spatial statistics analysis for FA showed a significant decrease in four regions for middle-aged group compared to young-aged group, in 22 regions for old-aged group compared to middle-aged group, and in 26 regions for old-aged group compared to young-aged group (P < 0.05). We found significantly lower WMV, FA, and mean diffusivity values in females than males and inverted-U trend for FA in males. We conclude differential age- and gender-related changes for structural WMV and WM diffusion indices.

Keywords: axial diffusivity; diffusion tensor imaging; fractional anisotropy; mean diffusivity; radial diffusivity; tract-based spatial statistics; white matter integrity.

Figure 1

Processing pipeline depicting our methodology. Right: T1-weighted MR images undergo segmentation (white matter, gray matter, and CSF) and volumetric calculation through SPM and VBM followed by statistical analysis. Left: Diffusion indices (FA, MD, RD, and AD) are extracted from DTI images through FDT toolbox followed by volumetric calculation. On the other side, diffusion maps are subjected to TBSS for voxel-wise statistical analysis. Abbreviations: CSF, cerebrospinal fluid; SPM, statistical parametric mapping; VBM, voxel-based morphometry; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity; AD, axial diffusivity; TBSS, tract-based spatial statistics.

Figure 2

Box plots of whole-brain white matter volume, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity in three age groups.

Figure 3

Box plots showing overall gender differences with whole-brain white matter volume, fractional anisotropy, mean, radial, and axial diffusivities.

Figure 4

Column graphs showing within-group gender differences and intergroup differences of male and female with whole-brain white matter volume and each diffusion index. The standard errors are shown with black band above the columns. Abbreviations: FA, fractional anisotropy; MD, mean diffusivity; AD, axial diffusivity; RD, radial diffusivity; WMV, white matter volume.

Figure 5

Statistical maps showing white matter clusters (red) where FA was significantly greater in young-aged > middle-aged adults, middle-aged > old-aged adults, old-aged > young-aged adults. Abbreviations: FA, fractional anisotropy; R, right; L, left.

Figure 6

Scatter plots of the whole-brain values of each diffusion index vs Whole-brain white matter volume. Abbreviations: FA, fractional anisotropy; MD, mean diffusivity; AD, axial diffusivity; RD, radial diffusivity; WMV, white matter volume.