Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals
ABSTRACT Background and Purpose 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 impair...
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| Format: | Article |
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Wiley
2025-05-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70521 |
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| author | Subin Lee Suhyeon Lee Ina Park Yeonsil Moon Younghee Yim Jongho Lee June Sic Kim Won‐Jin Moon |
| author_facet | Subin Lee Suhyeon Lee Ina Park Yeonsil Moon Younghee Yim Jongho Lee June Sic Kim Won‐Jin Moon |
| author_sort | Subin Lee |
| collection | DOAJ |
| description | ABSTRACT Background and Purpose 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. Materials and Methods 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. Results 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. Conclusions 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. |
| format | Article |
| id | doaj-art-77dc6ed56c604df79d4b9469b574cc95 |
| institution | OA Journals |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-77dc6ed56c604df79d4b9469b574cc952025-08-20T02:29:19ZengWileyBrain and Behavior2162-32792025-05-01155n/an/a10.1002/brb3.70521Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal IndividualsSubin Lee0Suhyeon Lee1Ina Park2Yeonsil Moon3Younghee Yim4Jongho Lee5June Sic Kim6Won‐Jin Moon7Laboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering Seoul National University Seoul South KoreaDepartment of Radiology Konkuk University Medical Center, Konkuk University School of Medicine Seoul South KoreaDepartment of Radiology Konkuk University Medical Center, Konkuk University School of Medicine Seoul South KoreaDepartment of Neurology Konkuk University Medical Center, Konkuk University School of Medicine Seoul South KoreaDepartment of Radiology Chung‐Ang University College of Medicine, Chung‐Ang University Hospital Seoul South KoreaLaboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering Seoul National University Seoul South KoreaClinical Research Institute Konkuk University Medical Center Seoul South KoreaDepartment of Radiology Konkuk University Medical Center, Konkuk University School of Medicine Seoul South KoreaABSTRACT Background and Purpose 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. Materials and Methods 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. Results 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. Conclusions 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.https://doi.org/10.1002/brb3.70521ironmemorymild cognitive impairmentquantitative susceptibility mapping |
| spellingShingle | Subin Lee Suhyeon Lee Ina Park Yeonsil Moon Younghee Yim Jongho Lee June Sic Kim Won‐Jin Moon Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals Brain and Behavior iron memory mild cognitive impairment quantitative susceptibility mapping |
| title | Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals |
| title_full | Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals |
| title_fullStr | Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals |
| title_full_unstemmed | Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals |
| title_short | Associations Between Cortical Iron Accumulation and Memory in Patients With Amnestic Mild Cognitive Impairment and in Cognitively Normal Individuals |
| title_sort | associations between cortical iron accumulation and memory in patients with amnestic mild cognitive impairment and in cognitively normal individuals |
| topic | iron memory mild cognitive impairment quantitative susceptibility mapping |
| url | https://doi.org/10.1002/brb3.70521 |
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