Age-related differences in multiple measures of white matter integrity: A diffusion tensor imaging study of healthy aging

Abstract

Diffusion tensor imaging (DTI) measures diffusion of molecular water, which can be used to calculate indices of white matter integrity. Early DTI studies of aging primarily focused on two global measures of integrity; the average rate (mean diffusivity, MD) and orientation coherence (fractional anisotropy, FA) of diffusion. More recent studies have added measures of water movement parallel (axial diffusivity, AD) and perpendicular (radial diffusivity, RD) to the primary diffusion direction, which are thought to reflect the neural bases of age differences in diffusion (i.e., axonal shrinkage and demyelination, respectively). In this study, patterns of age differences in white matter integrity were assessed by comparing younger and healthy older adults on multiple measures of integrity (FA, AD, and RD). Results revealed two commonly reported patterns (Radial Increase Only and Radial/Axial Increase), and one relatively novel pattern (Radial Increase/Axial Decrease) that varied by brain region and may reflect differential aging of microstructural (e.g., degree of myelination) and macrostructural (e.g., coherence of fiber orientation) properties of white matter. In addition, larger age differences in FA in frontal white matter were consistent with the anterior-posterior gradient of age differences in white matter integrity. Together, these findings complement other recent studies in providing information about patterns of diffusivity that are characteristic of healthy aging.

Figure 1

Statistical map showing white matter clusters (red) where FA was significantly greater in younger versus older adults, across four axial slices (panel A) and four sagittal slices (panel B). Axial slices are presented in radiological orientation (right = left). RLIC = retrolenticular part of the internal capsule.

Figure 2

The percent of age group difference in FA, calculated for each white matter cluster by dividing the group difference in FA (younger minus older adults) by the average FA for that cluster, is plotted as a function of each cluster's average y coordinate (in mm according to MNI space). As the regression line indicates, age‐related decreases in FA were significantly larger in anterior (panel B) versus posterior (panel A) clusters. This relationship was significant for the frequently reported superior clusters (closed circle) with z coordinates above or traversing zero, but did not attain significance for inferior clusters (open circles). Average y coordinates (from left to right) correspond to the following cluster: −63.5, left posterior corona radiata; −57.0, right posterior corona radiata; −53.5, right cerebellum; −51.5, left posterior pericallosal; −51.5, right posterior pericallosal; −26.5, right retrolenticular part of the internal capsule (RLIC); −26.0, left medial RLIC (mRLIC); −26.0, left RLIC; −25.0, right mRLIC; −22.5, left cerebral peduncle; −13.0, right inferior sagittal stratum; −11.0, left inferior sagittal stratum; 2.0, left external capsule; 2.5, right external capsule; 10.5, right superior longitudinal fasciculus; 16.5, left superior longitudinal fasciculus; 19.5, genu of the corpus callosum; 21.5, right superior corona radiata; 26.0, left superior corona radiata; 27.0, left frontal cluster; 34.5, right anterior/superior corona radiata; 36, right anterior pericallosal; 36.5, left anterior pericallosal; 38.5, left anterior/superior corona radiata; 41.0, right superior sagittal stratum; 43, left anterior/inferior corona radiata; 51.5, left superior sagittal stratum.