Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness

Abstract

It is well established that healthy aging is accompanied by structural changes in many brain regions and functional decline in a number of cognitive domains. The goal of this study was to determine (1) whether the regional distribution of age-related brain changes is similar in gray matter (GM) and white matter (WM) regions, or whether these two tissue types are affected differently by aging, and (2) whether measures of cognitive performance are more closely linked to alterations in the cerebral cortex or in the underlying WM in older adults (OA). To address these questions, we collected high-resolution magnetic resonance imaging (MRI) data from a large sample of healthy young adults (YA; aged 18-28) and OA (aged 61-86 years). In addition, the OA completed a series of tasks selected to assess cognition in three domains: cognitive control, episodic memory, and semantic memory. Using advanced techniques for measuring cortical thickness and WM integrity, we found that healthy aging was accompanied by deterioration of both GM and WM, but with distinct patterns of change: Cortical thinning occurred primarily in primary sensory and motor cortices, whereas WM changes were localized to regions underlying association cortices. Further, in OA, we found a striking pattern of region-specific correlations between measures of cognitive performance and WM integrity, but not cortical thickness. Specifically, cognitive control correlated with integrity of frontal lobe WM, whereas episodic memory was related to integrity of temporal and parietal lobe WM. Thus, age-related impairments in specific cognitive capacities may arise from degenerative processes that affect the underlying connections of their respective neural networks.

Figure 1

A) Voxel-wise t maps showing differences between YA and OA in FA overlaid on representative sagittal (left), coronal (middle), and axial (right) slices. Regions depicted in red-yellow indicate areas where FA was lower in OA compared to YA; regions depicted in blue indicate areas where FA was higher in OA compared to YA. B) Placement of manually defined ROIs. C) Effect sizes ([OA mean – YA mean]/pooled SD) for all ROIs; negative values are regions where FA was lower in OA compared to YA and positive values are area where FA was greater in OA; asterisks indicate significant differences between OA and YA (p < .05). Abbreviations: CC, corpus callosum; PFC, prefrontal cortex; OFC, orbitofrontal cortex; Sag Str, sagittal stratum.

Figure 2

A) Surface-based vertex-wise GLM maps showing differences between OA and YA in cortical thickness. Regions depicted in red-yellow indicate areas where cortex was thinner in OA compared to YA; regions depicted in blue indicate areas where cortex was thicker in OA compared to YA. B) Placement of manually defined cortical ROIs. C) Effect sizes ([OA mean – YA mean]/pooled SD) for all ROIs; negative values indicate regions with thinner cortex in OA, compared to YA, and positive values represent regions with thicker cortex in OA; asterisks indicate significant differences between OA and YA (p < .05). Abbreviations: MTG, middle temporal gyrus; ITG, inferior temporal gyrus; PFC, prefrontal cortex; OFC, orbitofrontal cortex; ACC, anterior cingulate cortex; PCC, posterior cingulate cortex; PcG, precentral gyrus; Calc, calcarine cortex.

Figure 3

Voxel-wise signed-r² maps for correlations between FA and composite scores on A) cognitive control tasks, and B) episodic memory tasks in OA. Positive correlations are shown in red, negative correlations in blue. C) Composite z scores on cognitive control and episodic memory tasks plotted against mean FA for frontal (▲, orange lines) and temporo-parietal (●, green lines) ROIs, bilaterally (see text for anatomical definitions). Significant correlations (p < 0.01) are indicated by solid lines, non-significant correlations by dashed lines. Due to the similar patterns of correlation, right and left ROIs are combined for graphical purposes.