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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Main Authors: Subin Lee, Suhyeon Lee, Ina Park, Yeonsil Moon, Younghee Yim, Jongho Lee, June Sic Kim, Won‐Jin Moon
Format: Article
Language:English
Published: Wiley 2025-05-01
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.
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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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