Globus Pallidus Iron Relates to Cognitive Impairment in Alzheimer's Disease: Evidence From MRI-Based Meta-Analysis

Iron is essential for brain metabolism and cognitive functioning, but excessive levels during healthy and pathological aging can have detrimental effects. Although this notion was supported by several single studies, meta-analytic evidence in Alzheimer's disease (AD) is still scarce. Therefore, we performed a meta-analysis of 23 MRI experiments with, in total, 715 AD patients and 1130 healthy controls (HC). All studies employed iron sensitive markers in basal ganglia structures, thalamus, and hippocampus, together with the Mini-Mental-Status-Examination (MMSE) to quantify cognitive performance. In all regions of interest, significantly higher iron levels were present in people with AD compared to HC, with the most pronounced effects in the putamen followed by the caudate. Importantly, only globus pallidus iron levels were negatively correlated with MMSE performance in AD patients. Our results provide unique evidence that increases in iron levels, especially within basal ganglia structures, which provide a hub for cognitive information processing, are a characteristic hallmark of AD.