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阿尔茨海默病患者接受抗β淀粉样蛋白治疗后的淀粉样相关成像异常的检测与管理。

Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer's Disease Treated with Anti-Amyloid Beta Therapy.

机构信息

Jerome Barakos, Medical Imaging, Neuroscience, Bioclinica, 7707 Gateway Boulevard, 3rd Floor, Newark, CA 94560, USA. Tel: 415 515-3058, Fax: 415 753-9363. E-mail:

出版信息

J Prev Alzheimers Dis. 2022;9(2):211-220. doi: 10.14283/jpad.2022.21.

Abstract

Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer's disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.

摘要

淀粉样蛋白相关成像异常(ARIA)是在抗淀粉样蛋白β(Aβ)治疗阿尔茨海默病试验中报告的不良事件。本综述总结了现有关于 ARIA 的文献,包括 bapineuzumab、gantenerumab、donanemab、lecanemab 和 aducanumab 研究,涉及潜在的风险因素、检测和管理。ARIA 的病理生理学尚不清楚,但它可能与抗体与脑实质和血管中积累的 Aβ结合有关,导致血管壁完整性丧失和周围组织渗漏增加。放射学上,ARIA-E 被识别为脑实质中的血管源性水肿或软脑膜/脑沟中的脑沟液渗出,而 ARIA-H 是表现为微出血或表浅铁质沉着症的含铁血黄素沉积。在大多数情况下,ARIA 往往是短暂的和无症状的,通常发生在治疗早期,随着治疗的进行,风险会降低。关于在 ARIA 的影像学发现后继续给药的数据有限;因此,如果出现 ARIA,应谨慎继续治疗并定期监测。临床试验已经实施了管理方法,例如在 ARIA 的症状或影像学迹象缓解或治疗永久停止之前暂停治疗。ARIA 无需伴随治疗即可基本解决,并且没有关于 ARIA 潜在治疗方法的系统数据。鉴于抗 Aβ 治疗的可用性,ARIA 监测现在将在常规临床实践中实施。临床试验中使用的简单磁共振成像序列可能足以有效检测病例。提高临床医生和放射科医生对 ARIA 的认识和教育至关重要。

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