Differential effects of age and history of hypertension on regional brain volumes and iron

Abstract

Aging affects various structural and metabolic properties of the brain. However, associations among various aspects of brain aging are unclear. Moreover, those properties and associations among them may be modified by age-associated increase in vascular risk. In this study, we measured volume of brain regions that vary in their vulnerability to aging and estimated local iron content via T2* relaxometry. In 113 healthy adults (19-83 years old), we examined prefrontal cortex (PFC), primary visual cortex (VC), hippocampus (HC), entorhinal cortex (EC), caudate nucleus (Cd), and putamen (Pt). In some regions (PFC, VC, Cd, and Pt) age-related differences in iron and volume followed similar patterns. However, in the medial-temporal structures, volume and iron content exhibited different age trajectories. Whereas age-related volume reduction was mild in HC and absent in EC, iron content evidenced significant age-related declines. In hypertensive participants significantly greater iron content was noted in all examined regions. Thus, iron content as measured by T2* may be a sensitive index of regional brain aging and may reveal declines that are more prominent than gross anatomical shrinkage.

Figure 1

Definition of the regions of interest (ROI), indicated in red. Each ROI was marked on the T1-weighted image (first echo, TE = 10 ms, the a. panel throughout the figure), and copied to the T2* map (indexed as b. in the figure). T2* values that were computed from eight echoes were read from the T2* map. The figure presents two neocortical ROIs (1), two medial-temporal ROIs (2), and two neostriatal ROIs (3). In T2* maps, the values above 100ms were set to zero to make GM/WM more easily visible.

Figure 2

Volume and T2* as a function of age in the hippocampus and the entorhinal cortex.

Figure 3

Regression of volume and T2* on age in the neocortical regions: prefrontal and occipital. The correlation coefficient for the superior frontal gyrus (a part of the lateral prefrontal cortex) T2* is for the combination of linear and quadratic components. For the linear component only, r= −<.001.

Figure 4

Regressions of volume and T2* on age in the caudate nucleus and putamen.

Figure 5

Regional T2* differences between hypertensive and normotensive participants: Group means and standard errors of the means.

Figure 6

Calculated regional T2* correspond well to concentrations of iron (C) found in postmortem material (medians from multiple studies summarized in Haacke et al., 2005, Table 3). Note, that because there are no reports on the entorhinal cortex iron content, we used the reported hippocampal values. The values of T2* and C, though age-sensitive, are averaged across the respective life-span samples. Vertical bars are standard errors of T2* means. Abbreviations: Pt –putamen, Cd –caudate nucleus, VC –(primary) visual cortex, SFG –superior frontal gyrus, EC –entorhinal cortex, HC –hippocampus.