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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00904

Application of T1-/T2-weighted ratio mapping to elucidate intracortical demyelination process in the Alzheimer’s disease continuum

 Xiao Luo1,  Kaicheng Li1, Qingze Zeng1, Peiyu Huang1, Yeerfan Jiaerken1, Shuyue Wang1, Zhujing Shen1, Xiaojun Xu1, Jingjing Xu1, Chao Wang1, Linlin Kong2, Jiong Zhou2* and  Minming Zhang1*
  • 1Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, China
  • 2Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, China

Background:
The biological diagnosis criteria of the Alzheimer’s disease (AD) suggests that previous work may misclassify the cognitive impairment caused by other factors into AD. Consequently, re-assessing the imaging profile of AD continuum is needed. Considering the high vulnerability of cortical association fibers, we aimed to elucidate the cortical demyelination process in the AD continuum biologically defined.

Methods:
According to the biological diagnosis criteria, we determined the positive amyloid status (A+) as cerebrospinal fluid (CSF) amyloid1-42<192 pg/ml, Florbetapir Positron emission tomography (PET) composite standardized uptake value ratio (SUVR) >1.11. Also, the positive Tau status (T+) was determined as p-Tau181 >23 pg/ml. Based on the cognitive characterization, we further categorized 252 subjects into 27 cognitively unimpaired with normal AD biomarkers (A-T-, controls), 49 preclinical AD (A+T+), 113 AD with mild cognitive impairment (MCI) (A+T+), and 63 AD dementia (A+T+). We estimated the intracortical myelin content used the T1- and T2-weighted (T1W/T2W) ratio mapping. To investigate the sensitivity of the ratio mapping, we also utilized well-validated AD imaging biomarkers as the reference, including grey matter volume and Fludeoxyglucose PET (FDG-PET). Based on the general linear model, we conducted the voxel-wise two-sample T-tests between the controls and each group in the AD continuum.

Results:
Compared to the controls, the results showed that the preclinical AD patients exhibited decreased T1W/T2W ratio value in the right inferior parietal lobule (IPL); as the disease progresses, the prodromal AD patients demonstrated lower ratio value in bilateral IPL, with hippocampus (HP) atrophy. Lastly, the AD dementia patients exhibited decreased ratio value in bilateral IPL and hippocampus; also, we observed the bilateral temporal cortices atrophy and widespread decreased metabolism in the AD dementia patients. After corrected with grey volume, the results remained mostly unchanged.

Conclusion:
Our study implied the decreased right IPL T1W/T2W ratio might represent early AD-related demyelination in disease continuum. Additionally, we demonstrated that the T1W/T2W ratio mapping is an easy-to-implement and sensitive metric to assess the intracortical myelin content in AD, particularly in the early stage.

Keywords: Alzheimer’s disease continuum, inferior parietal lobule (IPL), Amyloid, Intracortical myelin, Preclinical Alzheimer’s disease.

Received: 05 Mar 2019; Accepted: 13 Aug 2019.

Copyright: © 2019 Luo, Li, Zeng, Huang, Jiaerken, Wang, Shen, Xu, Xu, Wang, Kong, Zhou and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jiong Zhou, Second Affiliated Hospital, School of Medicine, Zhejiang University, Neurology, Hangzhou, 310009, Zhejiang Province, China, Jionghuakai@zju.edu.cn
Prof. Minming Zhang, Second Affiliated Hospital, School of Medicine, Zhejiang University, Radiology, Hangzhou, 310009, Zhejiang Province, China, zhangminming@zju.edu.cn