Journal Article

Altered brain iron depositions from aging to Parkinson's disease and Alzheimer's disease: A quantitative susceptibility mapping study

Zeng, Qingze, Xu, Xiaojun, Wen, Jiaqi, Cao, Zhengye, Chen, Jingwen, Liu, Chunlei, Wei, Hongjiang, Li, Kaicheng, Wu, Jingjing, Gu, Luyan, Zhang, Minming, Bai, Xueqin, Zhang, Yuyao, Zhou, Cheng, Song, Zhe, Luo, Xiao, Zhang, Baorong, Guan, Xiaojun, Gao, Ting, Yan, Yaping, Wu, Haoting, Liu, Xiaocao, Pu, Jiali, Guo, Tao

2022

Overview

•Iron deposition significantly increases with aging in many subcortical nuclei, with uneven distribution within nuclei.•In PD, iron is progressively deposited in the substantia nigra and red nucleus.•In AD, iron is strongly deposited in caudate and putamen.•Regional iron deposition can delineate brain degeneration and predict the severity of neurodegenerative diseases. Brain iron deposition is a promising marker for human brain health, providing insightful information for understanding aging as well as neurodegenerations, e.g., Parkinson's disease (PD) and Alzheimer's disease (AD). To comprehensively evaluate brain iron deposition along with aging, PD-related neurodegeneration, from prodromal PD (pPD) to clinical PD (cPD), and AD-related neurodegeneration, from mild cognitive impairment (MCI) to AD, a total of 726 participants from July 2013 to December 2020, including 100 young adults, 189 old adults, 184 pPD, 171 cPD, 31 MCI and 51 AD patients, were included. Quantitative susceptibility mapping data were acquired and used to quantify regional magnetic susceptibility, and the resulting spatial standard deviations were recorded. A general linear model was applied to perform the inter-group comparison. As a result, relative to young adults, old adults showed significantly higher iron deposition with higher spatial variation in all of the subcortical nuclei (p < 0.01). pPD showed a high spatial variation of iron distribution in the subcortical nuclei except for substantia nigra (SN); and iron deposition in SN and red nucleus (RN) were progressively increased from pPD to cPD (p < 0.01). AD showed significantly higher iron deposition in caudate and putamen with higher spatial variation compared with old adults, pPD and cPD (p < 0.01), and significant iron deposition in SN compared with old adults (p < 0.01). Also, linear regression models had significances in predicting motor score in pPD and cPD (Rmean = 0.443, Ppermutation = 0.001) and cognition score in MCI and AD (Rmean = 0.243, Ppermutation = 0.037). In conclusion, progressive iron deposition in the SN and RN may characterize PD-related neurodegeneration, namely aging to cPD through pPD. On the other hand, extreme iron deposition in the caudate and putamen may characterize AD-related neurodegeneration.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Aging / Alzheimer Disease - diagnostic imaging / Alzheimer's disease / Brain - diagnostic imaging / Brain health / Brain mapping / Brain Mapping - methods / Brain research / Cognitive ability / Deep learning / Dementia / Humans / Iron / Iron metabolism / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Magnetic susceptibility / Metabolism / Movement disorders / Neurodegeneration / Neurodegenerative diseases / Parkinson Disease - diagnostic imaging / Parkinson's disease / Physiology / Putamen / Quantitative susceptibility mapping / Red nucleus / Regression analysis / Software / Spatial variations / Statistical analysis / Substantia nigra / Young Adult / Young adults