Age-related differences in iron content of subcortical nuclei observed in vivo: a meta-analysis

Abstract

Accumulation of non-heme iron in the brain has been proposed as a biomarker of the progressive neuroanatomical and cognitive declines in healthy adult aging. Postmortem studies indicate that iron content and lifespan differences therein are regionally specific, with a predilection for the basal ganglia. However, the reported in vivo estimates of adult age differences in iron content within subcortical nuclei are highly variable. We present a meta-analysis of 20 in vivo magnetic resonance imaging (MRI) studies that estimated iron content in the caudate nucleus, globus pallidus, putamen, red nucleus, and substantia nigra. The results of the analyses support a robust association between advanced age and high iron content in the substantia nigra and striatum, with a smaller effect noted in the globus pallidus. The magnitude of age differences in estimated iron content of the caudate nucleus and putamen partially depended on the method of estimation, but not on the type of design (continuous age vs. extreme age groups).

Figure 1

A plot of effect sizes for age differences in iron content of the putament (Pt). Sample size-corrected effect sizes (d) are shown with 95% confidence intervals and the median value across studies is marked with the dotted line. Confidence intervals not including zero indicates significant age-related difference.

Figure 2

A plot of effect sizes for age differences in iron content of the caudate nucleus (Cd). Sample size-corrected effect sizes (d) are shown with 95% confidence intervals and the median value across studies is marked with the dotted line. Confidence intervals not including zero indicates significant age-related difference.

Figure 3

A plot of effect sizes for age differences in iron content of the globus pallidus (GP). Sample size-corrected effect sizes (d) are shown with 95% confidence intervals and the median value across studies is marked with the dotted line. Confidence intervals not including zero indicates significant age-related difference.

Figure 4

A plot of effect sizes for age differences in iron content of the red nucleus (RN). Sample size-corrected effect sizes (d) are shown with 95% confidence intervals and the median value across studies is marked with the dotted line. Confidence intervals not including zero indicates significant age-related difference.

Figure 5

A plot of effect sizes for age differences in iron content of the substantia nigra (SN). Sample size-corrected effect sizes (d) are shown with 95% confidence intervals and the median value across studies is marked with the dotted line. Confidence intervals not including zero indicates significant age-related difference.