Access Type

Open Access Dissertation

Date of Award

January 2014

Degree Type


Degree Name




First Advisor

Naftali Raz


Accumulation of non-heme iron in the brain has been theorized as a cellular mechanism underlying global neural and cognitive decline in normal aging and neurodegenerative disease. Relatively few studies of brain iron in normal aging exist and extant studies are almost exclusively cross-sectional. Here, I estimated iron content via T2* and measured volumes in several brain regions in two independent samples of healthy adults. The first sample (N = 89) was measured twice with a two-year delay; and the second sample (N = 32) was assessed four times over a span of 7 years. Latent models estimated change in iron and volume, and the effects of cardiovascular risk factors as modifiers of change trajectories. Iron significantly increased (T2* decreased) over time in the basal ganglia, but not in the hippocampus. Accumulation of iron accounted for shrinkage in the striatum. Elevated metabolic syndrome risk indicators were associated with greater iron at baseline, which accounted for individual differences in shrinkage. Increase in caudate iron content was associated directly with lesser improvement in virtual Morris water maze navigation, and indirectly via shrinkage with lesser improvement in verbal working memory. This study present the first longitudinal evidence in support of iron as a biomarker of age-related decline in regional volume and cognition.