The association between higher order abilities, processing speed, and age are variably mediated by white matter integrity during typical aging

Abstract

Although aging is associated with changes in brain structure and cognition it remains unclear which specific structural changes mediate individual cognitive changes. Several studies have reported that white matter (WM) integrity, as assessed by diffusion tensor imaging (DTI), mediates, in part, age-related differences in processing speed (PS). There is less evidence for WM integrity mediating age-related differences in higher order abilities (e.g., memory and executive functions). In 165 typically aging adults (age range 54-89) we show that WM integrity in select cerebral regions is associated with higher cognitive abilities and accounts variance not accounted for by PS or age. Specifically, voxel-wise analyses using tract-based spatial statistics (TBSS) revealed that WM integrity was associated with reasoning, cognitive flexibility and PS, but not memory or word fluency, after accounting for age and gender. While cerebral fractional anisotropy (FA) was only associated with PS; mean (MD), axial (AD) and radial (RD) diffusivity were associated with reasoning and flexibility. Reasoning was selectively associated with left prefrontal AD, while cognitive flexibility was associated with MD, AD and RD throughout the cerebrum. Average WM metrics within select WM regions of interest accounted for 18% and 29% of the variance in reasoning and flexibility, respectively, similar to the amount of variance accounted for by age. WM metrics mediated ~50% of the age-related variance in reasoning and flexibility and different proportions, 11% for reasoning and 44% for flexibility, of the variance accounted for by PS. In sum, (i) WM integrity is significantly, but variably, related to specific higher cognitive abilities and can account for a similar proportion of variance as age, and (ii) while FA is selectively associated with PS; while MD, AD and RD are associated with reasoning, flexibility and PS. This illustrates both the anatomical and cognitive selectivity of structure-cognition relationships in the aging brain.

Figure 1

(A) Skeletal WM regions of interest (ROI). Areas are shown in the left hemisphere only except for regions of the corpus callosum. Inferior and superior longitudinal fasciculi (ILF and SLF), cingulate gyrus (CG), uncinate fasciculus (UNC), anterior thalamic radiation (ATR), corpus callosum genu (CC-G), body (CC-B) and splenium (CC-S). (B) Areas where lower reasoning scores are associated with higher skeletal AD after accounting for the effects of age and gender. (C) Areas where lower flexibility scores are associated with higher skeletal AD after accounting for the effects of PS, age and gender. Depicted slices in (B) and (C) are the same and correspond to MNI z-values of -16mm, -2mm, 12mm, 26mm and 40mm.