Assessment of brain iron accumulation in Alzheimer's disease with quantitative susceptibility mapping

Abstract

AbstractBackgroundEmerging evidence suggests that regional iron accumulation is involved in the early pathology of Alzheimer’s Disease (AD), which can be evaluated using quantitative susceptibility mapping (QSM). Therefore, the purpose of this study was to evaluate QSM as an early imaging biomarker in AD by comparing regional iron accumulation using QSM in patients with AD, mild cognitive impairment (MCI) and cognitively unimpaired (CU) subjects.MethodThirty‐seven patients with AD, twenty patients with MCI, and forty‐three CU subjects were recruited. All subjects received MRI QSM scans. All QSM images were reconstructed using NMEDI method. Using one‐way analysis of variance (ANOVA) test, the difference in regional iron accumulation between the three groups was studied in the regions of interest (ROI) including bilateral caudate nucleus and putamen. Pairwise multiple comparison was implemented using the least significant difference (LSD) method. For whole brain analysis, we applied a voxel‐based analysis using ANOVA followed by a post hoc analysis. A significant level of family‐wise error (FWE) corrected p < 0.05 with a cluster size of 30 voxels was applied to locate brain regions with significant differences among three groups. We used paired sample t test within 6‐month follow‐up data to see if there is any difference.ResultBased on ROI analysis, average susceptibility of the bilateral caudate and left putamen was significantly different among groups (p<0.001, respectively). Maximal susceptibility of the left caudate was significantly different among groups (p<0.001). For the whole brain analysis, significant difference in iron accumulation among AD, MCI and CU was found in parahippocampus, caudate, putamen, insula, cingulate gyrus, cuneus, precuneus, angular gyrus, thalamus, fusiform, lingual gyrus, corpus callosum, cortex and subcortical white matter, some cerebellum structures and so on. No significant difference was detected with the follow‐up data in each group.ConclusionThis study described brain iron accumulation patterns using QSM during AD progression. This may reveal secondary neuronal changes due to pathologic processes (e.g. oxidative stress) in AD. In addition, this study is the first to observe QSM changes in certain cerebellar regions. Further study is needed to confirm this finding.