Globus pallidus iron relates to cognitive impairment in Alzheimer‘s disease: Evidence from MRI-based meta-analysis

BACKGROUND Iron plays an essential role in brain metabolism and, therefore, cognitive functioning. However, region specific iron level increases during healthy and, even more so, pathological aging, in particular Alzheimer’s disease, can have detrimental effects. Although this notion has been supported by several single studies, meta-analytic evidence of a relationship between iron levels, as measured with in vivo MRI, and Alzheimer's disease (AD) is still missing.METHODS We used a meta-analytic approach of 22 in vivo MRI experiments with, in total, 685 AD patients and 1104 healthy controls (HC). All studies employed iron sensitive markers, such as R2* or QSM, and reported effects in specific brain regions, including the putamen, caudate nucleus, globus pallidus, hippocampus, and thalamus, that were further analyzed here. We also investigated the relationship between iron levels in AD and cognitive performance as measured with the Mini-Mental-Status-Examination (MMSE).RESULTS In all regions of interest, higher iron level were significant in AD compared to HC, with most pronounced effects in the putamen followed by the caudate. Importantly, only in the globus pallidus iron levels showed a negative correlation with MMSE performance in AD patients. CONCLUSION Our results provide unique evidence for the notion that iron level increases, especially within basal ganglia structures, which provide a hub for cognitive information processing, are a characteristic hallmark of AD. While this may relate to neurodegeneration, amyloid plaques and tau pathologies, our findings suggest that iron level increases can help to explain and possibly predict cognitive decline in AD.