Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study
- Affiliations
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- 1Department of Radiology, Konkuk University Medical Center, Seoul, Republic of Korea
- 2Laboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea
- 3Department of Neurology, Konkuk University Medical Center, Seoul, Republic of Korea
- 4Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
Abstract
Objective
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.
Materials and Methods
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).
Results
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.
Conclusion
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.