Accumulation of iron in the putamen predicts its shrinkage in healthy older adults: A multi-occasion longitudinal study

Accumulation of non-heme iron is believed to play a major role in neurodegeneration of the basal ganglia. In healthy aging, however, the temporal relationship between change in brain iron content and age-related volume loss is unclear. Here, we present the first long-term longitudinal multi-occasion investigation of changes in iron content and volume in the neostriatum in a sample of healthy middle-aged and older adults (N=32; ages 49–83years at baseline). Iron content, estimated via R2* relaxometry, increased in the putamen, but not the caudate nucleus. In the former, the rate of accumulation was coupled with change in volume. Moreover, greater baseline iron content predicted faster shrinkage and smaller volumes seven years later. Older age partially accounted for individual differences in neostriatal iron content and volume, but vascular risk did not. Thus, brain iron content may be a promising biomarker of impending decline in normal aging. •Iron-related oxidative stress is a proposed mechanism of brain aging.•Neostriatal iron content and volume were assessed multiple times over seven years.•Middle-aged and older adults showed iron accumulation in putamen but not caudate.•Putamen iron accumulation preceded and predicted shrinkage.•Greater baseline iron predicted faster shrinkage and greater loss after seven years.