Spatial-temporal interactions between white matter hyperintensities and multiple pathologies across the Alzheimer's disease continuum

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-04-29 DOI:10.1002/alz.70098

Li Liang, Wei Liu, Youping Zhong, Tengfei Guo, Chenfei Ye, Ting Ma

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引用次数: 0

Abstract

INTRODUCTION

The interactive relationships between Alzheimer's disease (AD) and white matter hyperintensities (WMHs) in multiscale brain structural networks still need to be clarified.

METHODS

Based on subjects enrolled from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, regional WMHs, amyloid beta (Aβ) accumulation, and microstructural changes detected by diffusion weighted imaging (DWI) in multiscale brain networks were modeled by time-evolving graphs; their interactive relationships were further investigated using Granger causality after constructing pseudo-time subject sequences.

RESULTS

In up to 86% of the extracted pseudo-time subject sequences, Aβ was determined to be the Granger cause of WMHs in the structural connectivity of the inferior longitudinal fasciculus (ILF). Meanwhile WMHs were significantly correlated with microstructural changes measured by reduced fractional anisotropy in the inferior fronto-occipital fasciculus, ILF, and cingulum, which Granger causality pathways detected in 91%, 94%, and 93% of pseudo-time subject sequences, respectively.

DISCUSSION

These findings provide novel insights for understanding the multiscale space-time interactions between WMHs and AD pathologies.

Highlights

This study proposed time-evolving graph modeling of heterogeneous disease markers (amyloid beta [Aβ], white matter hyperintensities [WMHs], and microstructural changes of white matter tracts) across the Alzheimer's disease (AD) continuum to investigate their complex interactions in multiscale brain structural networks.
Regional accumulation of Aβ promoted WMH progression in subnetworks connected by the inferior longitudinal fasciculus (ILF).
Regional WMHs were strongly associated with bundle-specific microstructural changes in the ILF, inferior fronto-occipital fasciculus, and cingulum.
These results might provide novel insights for understanding the interactive relationship between cerebral small vessel disease and AD.

Abstract Image

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白质高强度与阿尔茨海默病连续体中多种病理之间的时空相互作用

在多尺度脑结构网络中，阿尔茨海默病（AD）与白质高强度（WMHs）之间的相互作用关系仍有待明确。方法基于从阿尔茨海默病神经影像学倡议（ADNI）数据库中招募的受试者，通过扩散加权成像（DWI）在多尺度脑网络中检测到的区域wmh、β淀粉样蛋白（Aβ）积累和微结构变化，通过时间演化图建模；在构建伪时间主题序列后，运用格兰杰因果关系进一步研究其交互关系。结果在高达86%的伪时间受试者序列中，Aβ被确定为下纵束（ILF）结构连通性中wmh的格兰杰原因。同时，WMHs与额枕下束、ILF和扣带的微结构变化显著相关，格兰杰因果通路分别在91%、94%和93%的假时间受试者序列中检测到这种变化。这些发现为理解wmh与AD病理之间的多尺度时空相互作用提供了新的见解。本研究提出了跨阿尔茨海默病（AD）连续体的异质疾病标志物（β淀粉样蛋白[Aβ]，白质高强度[WMHs]和白质束微结构变化）的时间演化图模型，以研究它们在多尺度大脑结构网络中的复杂相互作用。Aβ的区域性积累促进了由下纵束（ILF）连接的亚网络的WMH进展。区域性wmh与ILF、额枕下束和扣带束特异性微结构变化密切相关。这些结果可能为理解脑血管病与AD之间的相互作用关系提供新的见解。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.