Quantitative susceptibility mapping demonstrates different patterns of iron overload in subtypes of early-onset Alzheimer's disease.

Abstract

We aimed to define brain iron distribution patterns in subtypes of early-onset Alzheimer's disease (EOAD) by the use of quantitative susceptibility mapping (QSM). EOAD patients prospectively underwent MRI on a 3-T scanner and concomitant clinical and neuropsychological evaluation, between 2016 and 2019. An age-matched control group was constituted of cognitively healthy participants at risk of developing AD. Volumetry of the hippocampus and cerebral cortex was performed on 3DT1 images. EOAD subtypes were defined according to the hippocampal to cortical volume ratio (HV:CTV). Limbic-predominant atrophy (LP_MRI) is referred to HV:CTV ratios below the 25^th percentile, hippocampal-sparing (HpSp_MRI) above the 75^th percentile, and typical-AD between the 25^th and 75^th percentile. Brain iron was estimated using QSM. QSM analyses were made voxel-wise and in 7 regions of interest within deep gray nuclei and limbic structures. Iron distribution in EOAD subtypes and controls was compared using an ANOVA. Sixty-eight EOAD patients and 43 controls were evaluated. QSM values were significantly higher in deep gray nuclei (p < 0.001) and limbic structures (p = 0.04) of EOAD patients compared to controls. Among EOAD subtypes, HpSp_MRI had the highest QSM values in deep gray nuclei (p < 0.001) whereas the highest QSM values in limbic structures were observed in LP_MRI (p = 0.005). QSM in deep gray nuclei had an AUC = 0.92 in discriminating HpSp_MRI and controls. In early-onset Alzheimer's disease patients, we observed significant variations of iron distribution reflecting the pattern of brain atrophy. Iron overload in deep gray nuclei could help to identify patients with atypical presentation of Alzheimer's disease. • In early-onset AD patients, QSM indicated a significant brain iron overload in comparison with age-matched controls. • Iron load in limbic structures was higher in participants with limbic-predominant subtype. • Iron load in deep nuclei was more important in participants with hippocampal-sparing subtype.