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. 2013 Jul;23(7):1533-41.
doi: 10.1093/cercor/bhs139. Epub 2012 May 29.

The role of hippocampal iron concentration and hippocampal volume in age-related differences in memory

Karen M Rodrigue  1 , Ana M Daugherty, E Mark Haacke, Naftali Raz
Affiliations

The role of hippocampal iron concentration and hippocampal volume in age-related differences in memory

Karen M Rodrigue et al. Cereb Cortex. 2013 Jul.

Abstract

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.

Keywords: T2*; aging; brain; hippocampus; memory.

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Figures

Figure 1.
Figure 1.
A model that tests Cd T2* and volume as alternate neural correlates of age-related memory deficits to HC measures. Abbreviations: Cd—caudate nucleus, LMI—logical memory, immediate recall; LMD—logical memory, delayed recall; NamesI—memory for names, immediate recall; NamesD—memory for names, delayed recall. Significant paths are shown in bold and * indicates significance at P < 0.05.
Figure 2.
Figure 2.
A model that tests VC T2* and volume associations with age-related memory deficits as a control comparison. Significant paths are shown in bold and * indicates significance, P < 0.05. Abbreviations: VC—primary visual cortex.
Figure 3.
Figure 3.
A scatter plot and memory performance gradient in the space of 3 predictors: age, HC iron concentration (T2*), and HC volume. Standardized (Z) scores are displayed on all axes. Higher scores indicate younger age, lesser iron concentration (longer T2*), and larger volume. The plane represents memory performance (latent composite scores) with brown indicating the highest and pink/purple the lowest scores.
Figure 4.
Figure 4.
Direct age effects model. Significant paths are shown in bold and * indicates significance at P < 0.05.
Figure 5.
Figure 5.
Dual indirect path model. Significant paths are shown in bold and * indicates significance at P < 0.05.
Figure 6.
Figure 6.
Single indirect path A model. Significant paths are shown in bold and * indicates significance at P < 0.05.
See this image and copyright information in PMC

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