Age and sex related differences in subcortical brain iron concentrations among healthy adults

Abstract

Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo Quantitative Susceptibility Mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of Structural Equation Models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren & Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person age related changes.

7T Brain MRS in HIV Infection: Correlation with Cognitive Impairment and Performance on Neuropsychological Tests

“…Lack of significant findings may be in part due to the generally lower spectral quality obtained in this region due to magnetic susceptibility effects from bone/air/tissue interfaces proximal to the anterior temporal lobe, as well as partial volume with surrounding tissue due to the small size of the hippocampus. Spectral quality was also lower in the basal ganglia because of the high iron content of the globus pallidus and putamen which is known to increase line widths in MR spectra from this region 56–58 ; this may have also contributed to the lack of significant group differences or neurocognitive correlations detectable in this region.…”

Stability of R2* and quantitative susceptibility mapping of the brain tissue in a large scale multi-center study

“…The considerably smaller level of variance as compared to previous studies is attributed to the consistent imaging setup across all the sites. The level of stability varied among different ROIs and subjects, as attributed to different chemical compositions and subjects’ pathological conditions6.…”

“…As has been shown, the R2* and susceptibility contrast in the white matter and grey matter are mainly contributed by the myelin and iron respectively, which are important biomarker for studying the brain’s development and neurological disorders. They have been applied in a variety of studies including ageing678, functional study9, perfusion10, Parkinson disease11, Alzheimer disease12, calcification13, multiple sclerosis1415, etc.…”

Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential Biomarker

“…To identify the brain iron deposition in svMCI subjects correlating with the severity of cognitive impairment according to the z -score, the correlations the susceptibility values of each brain region showed group deference and the composite z -score, memory z -score, language z -score, attention-executive z -score and visuospatial z -score were assessed partial using correlation analysis, with patient age and gender as covariates (Persson et al, 2015). …”