正常衰老和多种神经系统疾病中正常白质的心室周围梯度

IF 13 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of Advanced Research Pub Date : 2025-09-24 DOI:10.1016/j.jare.2025.08.059

Zhizheng Zhuo, Xiaolu Xu, Decai Tian, Runzhi Li, Yutong Bai, Yulu Shi, Siyao Xu, Shan Lv, Guanmei Cao, Geli Hu, Jun Xu, Jianguo Zhang, Fu-Dong Shi, Declan Chard, Frederik Barkhof, Sven Haller, Xinghu Zhang, Yunyun Duan, Yaou Liu

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引用次数: 0

摘要

在多发性硬化症中发现了一种潜在的炎症相关的脑室周围白质（NAWM）异常，但它在正常衰老和其他神经系统疾病中的存在尚不清楚。目的：研究NAWM异常的心室周围梯度是否发生在正常衰老和其他神经系统疾病中。方法共纳入阿尔茨海默病290例、帕金森病262例、脑血管病154例、多发性硬化症212例，以及有MR弥散图像的年轻健康对照（hc） 344例、中年hc 344例、老年hc 398例。采用线性混合模型计算NAWM中归一化神经突密度（NDI）和取向弥散指数（ODI）的心室周围梯度（回归模型斜率）。分析其与其他MRI测量、临床变量和全脑基因表达的关系。进行了额外的敏感性和重复性分析。结果在老年hc和所有神经系统疾病组中均观察到标准化NDI和ODI的心室周围梯度。这种心室周围梯度在脉络膜丛体积（神经炎症的标志）与NDI或ODI、白质高强度体积、白质和灰质体积之间起中介作用，特别是在神经系统疾病中。它们与正常衰老和多种神经系统疾病的认知和身体表现有直接和间接的联系。我们观察到心室周围梯度与潜在的炎症、内皮和突触基因表达之间的相关性。敏感性和重复性分析证实了主要发现。结论与临床相关的脑室周围组织弥散特征梯度存在于正常衰老和多种神经系统疾病中，并具有共同的病理机制。

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Periventricular gradient of normal-appearing white matter in normal aging and multiple neurological diseases

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Periventricular gradient of normal-appearing white matter in normal aging and multiple neurological diseases

Introduction

A potential inflammation-associated periventricular gradient of normal-appearing white matter (NAWM) abnormalities has been identified in multiple sclerosis, but its presence in normal aging and other neurological diseases remains unclear.

Objectives

We aimed to determine whether a periventricular gradient of NAWM abnormalities occurs in normal aging and other neurological diseases.

Methods

A total of 290 Alzheimer’s disease, 262 Parkinson’s disease, 154 cerebral small vessel disease, 212 multiple sclerosis, as well as 344 younger healthy controls (HCs), 344 middle-aged HCs, and 398 older HCs with available MR diffusion images were included in this study. The periventricular gradient (the slope of regression model) in NAWM of normalized neurite density (NDI) and orientation dispersion indices (ODI), derived from diffusion MRI, was calculated using linear mixed models. Its associations with other MRI measures, clinical variables, and brain-wide gene expression were analyzed. Additional sensitivity and replication analyses were conducted.

Results

The periventricular gradients of both normalized NDI and ODI were observed in older HCs and all neurological disease groups. Such periventricular gradients play mediating roles between choroid plexus volume (a marker of neuroinflammation) and NAWM NDI or ODI, white matter hyperintensity volume, white and gray matter volumes, especially in neurological diseases. They exhibited both direct and indirect associations with cognitive and physical performance in normal aging and multiple neurological diseases. We observed correlations between periventricular gradients and underlying inflammatory, endothelial and synaptic gene expression. Sensitivity and replication analyses confirmed the main findings.

Conclusion

Clinically relevant periventricular gradients in tissue diffusion characteristics occur in normal aging and multiple neurological diseases, and share some underlying pathological mechanisms.

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来源期刊

Journal of Advanced Research Multidisciplinary-Multidisciplinary

CiteScore

21.60

自引率

0.90%

发文量

280

审稿时长

12 weeks

期刊介绍： Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.