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Age and sex related differences in subcortical brain iron concentrations among healthy adults. 2015

Ninni Persson, and Jianlin Wu, and Qing Zhang, and Ting Liu, and Jing Shen, and Ruyi Bao, and Mingfei Ni, and Tian Liu, and Yi Wang, and Pascal Spincemaille
Department of Psychology, Stockholm University, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden; Radiology, Weill Cornell Medical College, New York, NY, USA.

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 and 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 not only 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 changes in aging.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D008279 Magnetic Resonance Imaging Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. Chemical Shift Imaging,MR Tomography,MRI Scans,MRI, Functional,Magnetic Resonance Image,Magnetic Resonance Imaging, Functional,Magnetization Transfer Contrast Imaging,NMR Imaging,NMR Tomography,Tomography, NMR,Tomography, Proton Spin,fMRI,Functional Magnetic Resonance Imaging,Imaging, Chemical Shift,Proton Spin Tomography,Spin Echo Imaging,Steady-State Free Precession MRI,Tomography, MR,Zeugmatography,Chemical Shift Imagings,Echo Imaging, Spin,Echo Imagings, Spin,Functional MRI,Functional MRIs,Image, Magnetic Resonance,Imaging, Magnetic Resonance,Imaging, NMR,Imaging, Spin Echo,Imagings, Chemical Shift,Imagings, Spin Echo,MRI Scan,MRIs, Functional,Magnetic Resonance Images,Resonance Image, Magnetic,Scan, MRI,Scans, MRI,Shift Imaging, Chemical,Shift Imagings, Chemical,Spin Echo Imagings,Steady State Free Precession MRI
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011699 Putamen The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS. Nucleus Putamen,Nucleus Putamens,Putamen, Nucleus,Putamens,Putamens, Nucleus
D012012 Red Nucleus A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the CEREBELLUM via the superior cerebellar peduncle and a projection from the ipsilateral MOTOR CORTEX. Nucleus Ruber,Nucleus, Red
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002529 Cerebellar Nuclei Four clusters of neurons located deep within the WHITE MATTER of the CEREBELLUM, which are the nucleus dentatus, nucleus emboliformis, nucleus globosus, and nucleus fastigii. Dentate Nucleus,Nucleus Dentatus,Nucleus Emboliformis,Nucleus Fastigii,Nucleus Globosus,Amiculum of the Dentate Nucleus,Anterior Interposed Nucleus,Anterior Interpositus Nucleus,Central Nuclei,Deep Cerebellar Nuclei,Dentate Cerebellar Nucleus,Fastigial Cerebellar Nucleus,Fastigial Nucleus,Intracerebellar Nuclei,Lateral Cerebellar Nucleus,Medial Cerebellar Nucleus,Central Nucleus,Cerebellar Nuclei, Deep,Cerebellar Nucleus,Cerebellar Nucleus, Deep,Cerebellar Nucleus, Dentate,Cerebellar Nucleus, Fastigial,Cerebellar Nucleus, Lateral,Cerebellar Nucleus, Medial,Deep Cerebellar Nucleus,Emboliformis, Nucleus,Fastigii, Nucleus,Globosus, Nucleus,Interposed Nucleus, Anterior,Interpositus Nucleus, Anterior,Intracerebellar Nucleus,Nuclei, Central,Nuclei, Cerebellar,Nuclei, Deep Cerebellar,Nuclei, Intracerebellar,Nucleus Fastigius,Nucleus, Anterior Interposed,Nucleus, Anterior Interpositus,Nucleus, Central,Nucleus, Cerebellar,Nucleus, Deep Cerebellar,Nucleus, Dentate,Nucleus, Dentate Cerebellar,Nucleus, Fastigial,Nucleus, Fastigial Cerebellar,Nucleus, Intracerebellar,Nucleus, Lateral Cerebellar,Nucleus, Medial Cerebellar
D005260 Female Females
D005917 Globus Pallidus The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. Paleostriatum,Pallidum,Pallidums

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