Periventricular diffusivity reflects APOE ε4–modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-09-18 DOI:10.1002/alz.70659

Chang-Le Chen, Sang Joon Son, Noah Schweitzer, Hecheng Jin, Jinghang Li, Linghai Wang, Shaolin Yang, Chang Hyung Hong, Hyun Woong Roh, Bumhee Park, Jin Wook Choi, Young-Sil An, Sang Woon Seo, Yong Hyuk Cho, Sunhwa Hong, You Jin Nam, Davneet S. Minhas, Charles M. Laymon, George D. Stetten, Dana L. Tudorascu, Howard J. Aizenstein, Minjie Wu, Mayo Clinic Study of Aging

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引用次数: 0

Abstract

INTRODUCTION

Altered glymphatic-related fluid dynamics are increasingly recognized as a feature of Alzheimer's disease (AD). We generalized an established diffusion imaging framework to quantify periventricular diffusivity (PVeD), hypothesizing that fast diffusion signals in the periventricular region can reflect amyloid beta (Aβ) deposition across the AD continuum.

METHODS

Participants from two multi-site cohorts (n = 440 and 414), comprising cognitively unimpaired individuals, those with mild cognitive impairment, and patients with AD, were included. We tested and validated the association of PVeD with Aβ burden and core AD characteristics.

RESULTS

Lower PVeD was extensively associated with greater Aβ burden, neurodegeneration, cognitive impairment, and clinical severity in the clinical cohort. Importantly, the relationship between PVeD and Aβ burden was significantly modulated by apolipoprotein E (APOE) ε4 status; APOE ε4 carriers exhibited a replicable stronger negative association. Baseline PVeD also predicted longitudinal cognitive decline.

DISCUSSION

These findings suggest that periventricular diffusion signals reflect APOE ε4–modulated Aβ burden and cognitive decline in AD.

Highlights

An automated method for quantifying periventricular diffusivity (PVeD) is developed.
Lower PVeD is associated with higher amyloid load only in a mild cognitive impairment–dominant cohort.
Higher amyloid burden may mediate the link between lower PVeD and poorer cognitive outcomes in the clinical cohort.
Apolipoprotein E ε4 carriers show a reproducibly stronger inverse PVeD—amyloid association than non-carriers.
Baseline PVeD can predict longitudinal Mini-Mental State Examination decline in two independent cohorts.

Abstract Image

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脑室周围弥漫性反映了APOE ε4调节的淀粉样蛋白积累和阿尔茨海默病连续体中的认知障碍。

导论：与淋巴相关的流体动力学改变越来越被认为是阿尔茨海默病（AD）的一个特征。我们推广了已建立的弥散成像框架来量化心室周围弥散性（PVeD），假设心室周围区域的快速弥散信号可以反映淀粉样蛋白（Aβ）在AD连续体中的沉积。方法：参与者来自两个多站点队列（n = 440和414），包括认知功能未受损个体、轻度认知功能受损个体和AD患者。我们测试并验证了PVeD与Aβ负荷和AD核心特征的关联。结果：在临床队列中，较低的PVeD与较高的Aβ负担、神经退行性变、认知障碍和临床严重程度广泛相关。重要的是，载脂蛋白E (APOE) ε4状态显著调节PVeD与Aβ负荷的关系；APOE ε4携带者表现出可复制的较强负相关。基线PVeD也预测纵向认知能力下降。讨论：这些研究结果表明，APOE ε4调节的Aβ负担和AD患者的认知能力下降反映了心室周围扩散信号。重点：开发了一种量化心室周围弥散性（PVeD）的自动化方法。较低的pve仅在轻度认知障碍占主导地位的队列中与较高的淀粉样蛋白负荷相关。在临床队列中，较高的淀粉样蛋白负荷可能介导较低的PVeD与较差的认知结果之间的联系。载脂蛋白E ε4携带者与非载脂蛋白E ε4携带者相比，具有较强的可重复性。基线PVeD可以预测纵向迷你精神状态检查在两个独立队列中的下降。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.