Relationship between brain R₂ and liver and serum Iron concentrations in elderly men

Abstract

Studies of iron overload in humans and animals suggest that brain iron concentrations may be related in a regionally specific way to body iron status. However, few quantitative studies have investigated the associations between peripheral and regional brain iron in a normal elderly cohort. To examine these relationships, we used MRI to measure the proton transverse relaxation rate (R 2 ) in 13 gray and white matter brain regions in 18 elderly men (average age, 75.5 years) with normal cognition. Brain R 2 values were compared with liver iron concentrations measured using the FerriScan V R MRI technique and serum iron indices. R 2 values in high-iron gray matter regions were significantly correlated (positively) with liver iron concentrations (globus pallidus, ventral pallidum) and serum transferrin saturation (caudate nucleus, globus pallidus, putamen) measured concurrently with brain R 2 , and with serum iron concentrations (caudate nucleus, globus pallidus) measured three years before the current study. Our results suggest that iron levels in specific gray matter brain regions are influenced by systemic iron status in elderly men. Magn Reson Med 63:275-281,

No Genetic Overlap Between Circulating Iron Levels and Alzheimer’s Disease

“…Previous studies identified an association between iron accumulation in the basal ganglia of elderly men and peripheral iron measures [13]. However, only 9% of the variance of CSF ferritin can be explained by plasma ferritin [9], highlighting the separation between these compartments.…”

“…Quantitative MRI studies measuring the proton transverse relaxation rate (R 2 ) now allow iron concentrations to be assessed in the brain in vivo. One such study in cognitively normal elderly men found that iron levels in basal ganglia structures were correlated with serum iron measures [13]. In an investigation in the large Australian Imaging Biomarker and Lifestyle (AIBL) cohort of healthy controls, MCI and AD patients had disturbed brain iron metabolism reflected in the periphery by a decrease in plasma iron and hemoglobin [14], which was due to a deficiency of iron-loading onto transferrin [15].…”

A Cross-Sectional Community Study of Serum Iron Measures and Cognitive Status in Older Adults

“…For example, serum ferritin or transferrin saturation levels do not correlate well with hepatic iron content in most cases of hyperferritinemia [39]. In a study of older communitydwelling males (mean age 75.5 years), serum ferritin levels did not correlate with regional brain iron contents as gauged by magnetic resonance imaging proton transverse relaxation rate (R 2 ) [40]. Furthermore, in neuroferritinopathy, caused by mutations in ferritin light chain, abnormal iron deposition occurs in regions such as the basal ganglia despite low or normal serum ferritin [13,14,41] and neither venesection nor iron chelation is beneficial [41].…”

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

“…Women begin their postmenopausal years in a state of relative peripheral iron deficiency compared with men and their iron levels increase for the first 15-20 years after menopause without fully 'catching up' to those in men (Whitfield et al, 2003). As the peripheral iron levels can influence brain iron accumulation (Bartzokis et al, 2007c;House et al, 2010;Li et al, 2010), these peripheral effects could manifest in the brain. Thus, as the two genders approach older ages, it is possible that the already higher levels of iron observed in men push them into a toxic range earlier as they enter older ages, whereas women, who start with considerably lower iron levels, may initially experience a cognitive benefit from increasing postmenopausal iron levels.…”