Lee Subin, Lee Suhyeon, Park Ina, Moon Yeonsil, Yim Younghee, Lee Jongho, Kim June Sic, Moon Won-Jin
Laboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering, Seoul National University, Seoul, South Korea.
Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea.
Brain Behav. 2025 May;15(5):e70521. doi: 10.1002/brb3.70521.
Brain iron accumulation is recognized as a cause and therapeutic target in Alzheimer's disease (AD). We investigated the differences in both volume and iron accumulation between cognitively normal (CN) older adults and patients with amnestic mild cognitive impairment (aMCI). Additionally, we assessed which combination of these measures best explains the group differences in visual and verbal memory performance.
We retrospectively analyzed data from 48 patients with aMCI and 33 age-matched CN individuals. Structural differences were investigated using voxel-based comparisons of T1-weighted magnetic resonance images. Differences in iron accumulation were investigated using voxel-based comparisons of quantitative susceptibility mapping (QSM) images. Subsequently, significant clusters from these voxel-based analyses (amygdala, posterior cingulate cortex, precuneus, lateral occipital cortex, and pericalcarine cortex) were entered into a stepwise regression to predict verbal and visual memory scores, while accounting for age, sex, and education as covariates.
In comparison to CN, patients with aMCI had significantly lower scores in both verbal and visual memory tests (p < 0.001). The T1-weighted voxel-based morphometry (VBM) results showed significant hippocampal atrophy in the aMCI group relative to CN individuals. The QSM-VBM results showed increased iron accumulation in the amygdala, posterior cingulate cortex, precuneus, lateral occipital cortex, and pericalcarine cortex (FWE-corrected p < 0.05). Lower hippocampal volume (B = 2015.91, SE = 469.61, p < 0.001) and higher posterior cingulate cortex susceptibility (B = -189.63 SE = 89.11, p = 0.037) were significant predictors of verbal memory. For visual memory, higher lateral occipital susceptibility (B = -659. 96, SE = 253.03, p = 0.011) was significant imaging predictor.
These results suggest that iron accumulates in regions where atrophy has not yet occurred, suggesting that iron may serve as an earlier imaging marker of neurodegeneration compared to volume atrophy. Further studies are needed to investigate the longitudinal relationship between brain volume and iron accumulation during cognitive decline.
脑铁蓄积被认为是阿尔茨海默病（AD）的一个病因及治疗靶点。我们研究了认知正常（CN）的老年人与遗忘型轻度认知障碍（aMCI）患者在脑容量和铁蓄积方面的差异。此外，我们评估了这些指标的哪种组合能最好地解释视觉和言语记忆表现的组间差异。
我们回顾性分析了48例aMCI患者和33例年龄匹配的CN个体的数据。使用基于体素的T1加权磁共振图像比较来研究结构差异。使用基于体素的定量磁化率映射（QSM）图像比较来研究铁蓄积的差异。随后，将这些基于体素分析的显著簇（杏仁核、后扣带回皮质、楔前叶、枕外侧皮质和距状裂周围皮质）纳入逐步回归，以预测言语和视觉记忆分数，同时将年龄、性别和教育程度作为协变量考虑在内。
与CN相比，aMCI患者在言语和视觉记忆测试中的得分均显著较低（p < 0.001）。基于T1加权体素形态学测量（VBM）的结果显示，相对于CN个体，aMCI组海马体明显萎缩。QSM-VBM结果显示杏仁核、后扣带回皮质、楔前叶、枕外侧皮质和距状裂周围皮质中铁蓄积增加（FWE校正p < 0.05）。较低的海马体体积（B = 2015.91，SE = 469.61，p < 0.001）和较高的后扣带回皮质磁化率（B = -189.63，SE = 89.11，p = 0.037）是言语记忆的显著预测因素。对于视觉记忆，较高的枕外侧磁化率（B = -659.96，SE = 253.03，p = 0.011）是显著的影像学预测因素。
这些结果表明，铁在尚未发生萎缩的区域蓄积，这表明与体积萎缩相比，铁可能是神经退行性变的更早影像学标志物。需要进一步研究来探讨认知衰退过程中脑容量与铁蓄积之间的纵向关系。
