The Role of Hippocampal Iron Concentration and Hippocampal Volume in Age-Related Differences in Memory

The goal of this study was to examine the relationships between 2 age-sensitive indices of brain integrity-volume and iron concentration-and the associated age differences in memory performance. In 113 healthy adults (age 19-83 years), we measured the volume and estimated iron concentration in the hippocampus (HC), caudate nucleus (Cd), and primary visual cortex (VC) in vivo with T2* relaxation times, and assessed memory performance with multiple tests. We applied structural equation modeling to evaluate the contribution of individual differences in 2 indices of integrity, volume and T2*, to age-related memory variance. The results show that in healthy adults, age differences in memory can be explained in part by individual differences in HC volume that in turn are associated with differences in HC iron concentration. Lower memory scores were linked to smaller HC and higher HC iron concentration. No such associations were noted for Cd and VC. We conclude that the association between age-related declines in memory and reduced hippocampal volume may reflect the impact of oxidative stress related to increase in free iron concentration. Longitudinal follow-up is needed to test whether altered iron homeostasis in the HC is an early marker for age-related cognitive decline.