Iron content affects age group differences in associative learning-related fMRI activity.

Brain regions accumulate different amounts of iron with age, with older adults having higher iron in the basal ganglia (globus pallidus, putamen, caudate) relative to the hippocampus. This has important implications for functional magnetic resonance imaging (fMRI) studies in aging as the presence of iron may influence both neuronal functioning as well as the measured fMRI (BOLD) signal, and these effects will vary across age groups and brain regions. To test this hypothesis, the current study examined the effect of iron on age group differences in task-related activity within each basal nuclei and the hippocampus. Twenty-eight younger and 22 older adults completed an associative learning task during fMRI acquisition. Iron content (QSM, R*) was estimated from a multi-echo gradient echo sequence. As previously reported, older adults learned significantly less than younger adults and age group differences in iron content were largest in the basal ganglia (putamen, caudate). In the hippocampus (early task stage) and globus pallidus (late task stage), older adults had significantly higher learning-related activity than younger adults both before and after controlling for iron. In the putamen (late task stage), however, younger adults had significantly higher learning-related activity than older adults that was only seen after controlling for iron. These findings support the notion that age-related differences in iron influence both neuronal functioning and the measured fMRI signal in select basal nuclei. Moreover, previous fMRI studies in aging populations may have under-reported age group differences in task-related activity by not accounting for iron within these regions.