Independent effects of white matter lesion volume and APOE ɛ4 on ARIA-H in A4 Study

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-10-14 DOI:10.1002/alz.70751

Zahra Shirzadi, Aaron P. Schultz, Nazila Loghmani, Hyun-Sik Yang, Jeremy Ford, Roy Yaari, Michael Properzi, Wai-Ying W. Yau, Lei Liu, Michael S. Rafii, Michael C. Donohue, Adam M. Brickman, Clifford R. Jack Jr, Steven M. Greenberg, Paul Aisen, Reisa A. Sperling, Jasmeer P. Chhatwal, the A4 Study Team

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引用次数: 0

Abstract

INTRODUCTION

Increased white matter hyperintensity (WMH) volume is a common but non-specific finding in AD. This study investigates the effect of baseline WMH volume and APOE ε4 on magnetic resonance imaging (MRI)-visible hemorrhagic lesion emergence.

METHODS

We included A4 participants with 0/1 hemorrhagic lesion at baseline and >1 post-baseline MRI. We examined age, sex, amyloid, WMH, APOEε4, and cardiovascular risk as predictors of whether people would accrue ≥2 hemorrhagic lesions by their last MRI.

RESULTS

Among 1097 individuals with 0/1 baseline lesion, 120 had at least two hemorrhagic lesions on their last MRI. Elevated baseline WMH (odds ratio [OR] = 2.3, p = 0.002) and APOE ɛ4/ɛ4 (OR = 4.8, p < 0.001) independently predicted membership to this group. Both hetero- and homozygous APOE ɛ4 carriers with low WMH volume had a low risk of accumulating hemorrhagic lesions.

DISCUSSION

These results support the independent consideration of WMH and APOE ɛ4 in the natural history of hemorrhagic lesion accumulation and suggest that individuals with low WMH volume have a low short-term risk, irrespective of APOE genotype.

Trial Registration: NCT02008357

Highlights

Elevated baseline white matter lesion volume is related to the risk of ARIA-H emergence.
The effects of white matter lesion volume and APOE ɛ4 on ARIA-H are independent.
APOE ɛ4 carriers with low white matter lesion volume had a low risk of ARIA-H emergence.

Abstract Image

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A4脑白质病变体积和APOE α 4对ARIA-H的独立影响。

白质高强度（WMH）体积增加是AD常见但非特异性的表现。本研究探讨基线WMH体积和APOE ε4对磁共振成像（MRI）可见出血性病变出现的影响。方法：我们纳入了A4名基线时为0/1的出血性病变和基线后MRI为bb0 /1的患者。我们检查了年龄、性别、淀粉样蛋白、WMH、APOEε4和心血管风险作为人们是否会在最后一次MRI中出现≥2个出血性病变的预测因素。结果：在1097例基线病变为0/1的患者中，120例在最后一次MRI上至少有两个出血性病变。升高的基线WMH（比值比[OR] = 2.3, p = 0.002）和APOE ε 4/ ε 4 （OR = 4.8, p）。讨论：这些结果支持WMH和APOE ε 4在出血性病变积累的自然历史中的独立考虑，并提示WMH体积低的个体具有较低的短期风险，与APOE基因型无关。重点：基线白质病变体积升高与ARIA-H出现的风险相关。白质损伤体积和apoe4对ARIA-H的影响是独立的。APOE / 4携带者白质病变体积小，ARIA-H发生风险低。

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.