Effects of age and gender on white matter integrity

Abstract

Background and purpose: DTI provides a sensitive measure of change in the microstructure of white matter integrity. The purpose of our study was to investigate age-related changes, sex differences, and age-by-sex interactions in white matter integrity (FA, AD, and RD) across the whole brain with a large sample.

Materials and methods: A total of 857 healthy subjects (mean age = 56.1 ± 9.9 years; age range = 24.9-84.8 years) were included in this study. All subjects were scanned at 3T. With use of TBSS, we examined the effects of age and sex on FA, AD, and RD in the white matter.

Results: Global FA was negatively correlated with age (R(2) = 0.18, P < .0001), and global AD and RD were positively correlated with age (AD: R(2) = 0.02, P < .0001; RD: R(2) = 0.19, P < .0001). The correlation between age and global AD, however, was weak. Voxelwise analysis revealed a number of regions where FA was negatively correlated with age, with most of these regions showing a significant positive correlation between RD and age. There was a significant age-related FA increase in several white matter regions. Voxelwise analysis also revealed many regions where FA, AD, or RD differed between men and women; however, no region showed a significant interaction between age and sex.

Conclusions: Our results suggest that age-related changes in white matter integrity are more strongly associated with myelin sheath degeneration than with axonal degeneration, and that, in some specific regions, the number of remyelinated axons might increase with age. Our results also suggest that there are no sex differences in the aging process of the white matter.

Fig 1.

Effects of age on global FA, AD, and RD. A, Scatterplot of skeleton average FA versus age; B, scatterplot of skeleton average AD versus age; C, scatterplot of skeleton average RD versus age. A significant negative correlation was seen between age and global FA. A significant positive correlation was seen between age and global AD and between age and global RD; however, the correlation between age and global AD was weak. Simple linear regression curves (solid lines) and quadratic regression curves (dotted lines) are shown. The quadratic term was significant in AD and RD but not in FA.

Fig 2.

Effects of age on regional FA, AD, and RD. White matter tracts in red-yellow show a significant age-related increase in FA, AD, and RD. White matter tracts in blue-green show a significant age-related decrease in FA, AD, and RD.

Fig 3.

Scatterplots of mean FA (A), AD (B), and RD (C) versus age for voxels that showed a positive correlation between age and FA.

Fig 4.

Scatterplots of mean FA (A), AD (B), and RD (C) versus age for voxels that showed a negative correlation between FA and age.

Fig 5.

Effects of sex on regional FA, AD, and RD. White matter tracts in red-yellow show a significantly higher FA, AD, and RD in men compared with women. White matter tracts in blue-green show a significantly higher FA, AD, and RD in women compared with men.