Pattern of normal age-related regional differences in white matter microstructure is modified by vascular risk

Abstract

Even successful aging is associated with regional brain shrinkage and deterioration of the cerebral white matter. Aging also brings about an increase in vascular risk, and vascular impairment may be a potential mechanism behind the observed patterns of aging. The goals of this study were to characterize the normal age differences in white matter integrity in several brain regions across the adult life span and to assess the modifying effect of vascular risk on the observed pattern of regional white matter integrity. We estimated fractional anisotropy and diffusivity of white matter in nine cerebral regions of interest in 77 healthy adults (19-84 years old). There was a widespread reduction of white matter anisotropy with age, and prefrontal and occipital regions evidenced the greatest age-related differences. Diffusivity increased with age, and the magnitude of age differences increased beginning with the middle of the fifth decade. Vascular risk factors modified age differences in white matter integrity. Clinically diagnosed and treated arterial hypertension was associated with reduced white matter anisotropy and increased diffusivity beyond the effects of age. In the normotensive participants, elevation of arterial pulse pressure (a surrogate of arterial stiffness) was linked to deterioration of the white matter integrity in the frontal regions. Although the causal role of vascular risk in brain aging is unclear, the observed pattern of effects suggests that vascular risk may drive the expansion of age-related white matter damage from anterior to posterior regions.

Figure 1

ROIs used for DTI analyses. White matter regions of interest (ROIs manually drawn for obtaining FA and ADC values. (a) genu and splenium of corpus callosum, (b) bilateral anterior, genu, and posterior limbs of internal capsule, (c) bilateral superior prefrontal, (d) bilateral temporal stem, (e) bilateral superior posterior parietal, (f) bilateral optic radiations. Demarcation of the ROIs is displayed on the FA map.

Figure 2

Mean diffusion properties by region. a) fractional anisotropy, b) apparent diffusion coefficient. Error bars represent standard error of the mean. Note the differences in regional variance are greater in FA than in ADC.

Figure 3

Scatter plots and regression line of the association between age and regional fractional anisotropy (left panels) and apparent diffusion coefficient (right panels). The slopes of the regressions and the proportion variance explained for each panel is provided in Table 5.

Figure 3

Scatter plots and regression line of the association between age and regional fractional anisotropy (left panels) and apparent diffusion coefficient (right panels). The slopes of the regressions and the proportion variance explained for each panel is provided in Table 5.

Figure 3

Scatter plots and regression line of the association between age and regional fractional anisotropy (left panels) and apparent diffusion coefficient (right panels). The slopes of the regressions and the proportion variance explained for each panel is provided in Table 5.