Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study.

Abstract

Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (β = -216.21, P = 0.019) and insular cortex (β = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.