Table 1.
Demographic information for young (YA), middle-aged (MA) and older (OA) participants.
Table 2.
Quantitative measures of vascular risk in middle-age and older adults.
Table 3.
Health status in all participants.
Table 4.
Multi-variate general linear modeling of white-matter structural integrity, age and CBF: Significance of fit obtained from multi-variate general linear model including individual white-matter microstructural parameters as a function of CBF and age.
Table 5.
Multi-variate general linear modeling of white-matter structural integrity, age and CBF: Significance of fit obtained from multi-variate general linear model, where each white matter microstructural parameter (i.e. FA, AD or RD) is modeled a function of CBF and age with the remaining parameters as covariates.
Table 6.
Significance (p-value) obtained from two-factor ANOVA, assessing the relationship between FA, AD and RD in the callosum.
Figure 1.
Associations between age and white-matter microstructure.
(a) Aging was associated with significant decreases in fractional anisotropy (FA) (shown in blue, top panel) and increases in axial (AD) and radial diffusivity (RD) (shown in red-yellow), notably in the corpus callosum, corona radiata, cingulum, superior longitudinal fasciculus, internal capsule and uncinate fasciculus (the white matter skeleton is shown in green). (b) Relationship between age and DTI measures in the corpus callosum; the DTI measures were extracted from regions of interest defined in each participant’s native-space DTI volume. Each filled circle represents an individual subject, colour-coded for the subject’s global mean CBF. In the corpus callosum, the age-effect was most pronounced in the anterior portions. Significant age-correlations are indicated by asterisks. Note that while the CBF values show age trends (more blue to the right of the plots), there is considerable variability in CBF within age groups.
Figure 2.
Correlation between DTI parameters and mean cortical CBF, without controlling for age.
(a) The white-matter TBSS skeleton is shown in green. Cortical CBF was positively associated with white matter FA (shown in red-yellow), and negatively associated with AD and RD (shown in blue). Also, the association between DTI parameters and CBF was more evenly distributed throughout the callosum, also confirmed in the regional data plots in (b). (b) The relationship between mean cortical CBF and DTI measures in the corpus callosum, with the 95% confidence interval outlined by the shaded region. Each symbol represents one subject, colour-coded for age, with different symbols representing subjects with different vascular risk factors. The relationship between white-matter microstructure and CBF was also plotted for the risk-free subjects alone (dashed red lines), with the 95% confidence interval delimited by solid red lines. These fits show statistical similarity with the previous fits, evident from the overlapping intervals of confidence delimited by solid red lines. Significant CBF-correlations are indicated by asterisks (black for all subjects, red for risk-free subjects only). (c) Controlling for the presence of vascular risk resulted in limited changes in the observed associations between white-matter integrity and cortical CBF.
Figure 3.
Comparisons of correlations between age/CBF and white-matter microstructural integrity in the set of six ROIs showing the most significant effects, namely the corpus callosum (genu, body and splenium), the superior corona-radiata, external capsule and superior longitudinal fasciculus.
While FA was more significantly related to age, AD and RD were more significantly associated with CBF. The error bars represent the standard deviations, and asterisks indicate statistically significant differences between the age- and CBF associations.
Figure 4.
The correlation between DTI parameters and global cortical CBF, controlling for age.
(a) The white-matter skeleton is shown in green. The resulting associations (positive shown in red-yellow, negative shown in blue), were well-defined and consistent with the findings when not controlling for age. There was substantial overlap between regions showing positive FA associations and negative RD associations with CBF. (b) CBF-associations in a restricted age range. As an alternate way of assessing age-independence in the CBF-DTI associations, parameters of white-matter structural integrity were significantly correlated with mean cortical CBF even when limited to an age-range between 25 and 55 years. Data is shown for the genu of the corpus callosum. Again, each symbol represents one subject, colour-coded for age.
Figure 5.
Surface-based analyses of associations between regional DTI parameters in the corpus callosum and cortical CBF.
Significant positive associations are shown in orange-yellow, inverse associations are shown in blue. (a) Significant positive and spatially specific associations between FA and CBF can be seen. In contrast, AD and RD were negatively correlated with cortical CBF. (b) Strong associations remained after statistically controlling for age in the analyses. Regional associations did not follow patterns of known anatomy based on white-matter fibre trajectories or known vascular structure. However, cortical regions where CBF was associated with white matter integrity did exhibit qualitative similarities with the medial regions within the “default-mode” brain network.