White matter in aging and cognition: a cross-sectional study of microstructure in adults aged eighteen to eighty-three

Abstract

Structural brain change and concomitant cognitive decline are the seemingly unavoidable escorts of aging. Despite accumulating studies detailing the effects of age on the brain and cognition, the relationship between white matter features and cognitive function in aging have only recently received attention and remain incompletely understood. White matter microstructure can be measured with diffusion tensor imaging (DTI), but whether DTI can provide unique information on brain aging that is not explained by white matter volume is not known. In the current study, the relationship between white matter microstructure, age, and neuropsychological function was assessed using DTI in a statistical framework that employed white matter volume as a voxel-wise covariate in a sample of 120 healthy adults across a broad age range (18-83). Memory function and executive function were modestly correlated with the DTI measures while processing speed showed the greatest extent of correlation. The results suggest that age-related white matter alterations underlie age-related declines in cognitive function. Mean diffusivity and fractional anisotropy in several white matter brain regions exhibited a nonlinear relationship with age, while white matter volume showed a primarily linear relationship with age. The complex relationships between cognition, white matter microstructure, and white matter volume still require further investigation.

Figure 1

Relationship between total white matter volume (adjusted for total intracranial volume, gender, and education) and age. The cross-sectional pattern of white matter volume across the age span from eighteen years of age to eighty-three appears to follow a non-linear course. The linear fit is shown with a solid line and the quadratic fit is shown with a hatched line.

Figure 2

Relationship between regional white matter volume and age, as assessed using voxel-wise analysis. Linear regression was used in a cross-sectional sample to examine the relationship between white matter volume and age. Total intracranial volume, gender, and education, were included as covariates of no interest in the regression analysis. As can be seen on the glass brain on the left, frontal, parietal, temporal, and occipital white matter volume showed a negative relationship with age. In addition, brain stem, corpus callosum, and cerebellar white matter volume showed a negative relationship with age. Colors are representative of a T-score, shown by the color bar on the bottom right.

Figure 3

Relationship between regional fractional anisotropy (FA) and age, assessed using voxel-wise analysis, controlling for white matter volume. There was a negative relationship between FA and age in several brain white matter tracts. As can be seen in the glass brain on the left, frontal white matter was particularly affected, but age effects on FA could be seen throughout the brain, including extensive portions of the corpus callosum, inferior fronto-occipital fasciculus, superior and inferior longitudinal fasciculus, internal capsule, anterior, superior, and posterior corona radiata, portions of the cingulum and posterior thalamic radiations.

Figure 4

Voxel-wise comparison: linear and non-linear relationship between FA and age. Fractional anisotropy demonstrated a significantly greater non-linear relationship with age compared to a linear relationship, primarily in posterior brain regions such as the splenium of the corpus callosum, large bilateral regions of occipital white matter, bilateral cerebellar white matter, right inferior fronto-occipital fasciculus, and right posterior corona radiata. Small anterior regions also showed a significant difference between the two slopes, including left anterior thalamic radiation, left superior corona radiata, and the right anterior limb of the internal capsule. Colors are representative of a T-score, shown by the color bar in the top left

Figure 5

Voxel-wise comparison: linear and non-linear relationship between MD and age. Shown on the left are the white matter regions where mean diffusivity demonstrated a significantly greater non-linear relationship with age compared to a linear relationship, including the corpus callosum, cingulum, uncinate, superior and inferior longitudinal fasciculi, superior and inferior fronto-occipital fasciculi, internal and external capsule, anterior and posterior thalamic radiations, and short association fibers in frontal, temporal, parietal, and occipital white matter. Colors represent T-scores indicated in the color bar. On the right is a plot of mean diffusivity against age in the external capsule. The linear fit is shown with a solid line and the quadratic fit is shown with a hatched line.

Figure 6

Relationship between white matter microstructure and processing speed. Of the cognitive domains, processing speed showed the greatest extent of relationship to the diffusion tensor imaging measures; the extent can be seen in the glass brain on the top. Regions where mean diffusivity was positively correlated with performance on Trails A included bilateral anterior corona radiata, bilateral superior fronto-occipital fasciculus, bilateral superior longitudinal fasciculus, bilateral internal capsule, posterior cingulum, right inferior fronto-occipital fasciculus, and small portions of bilateral posterior corona radiata. The colors in the sagittal section on the left represent T-scores, indicated by the color bar on the top left.