Amyloid-related imaging abnormalities

Amyloid-related imaging abnormalities, abbreviated ARIA, are characteristic abnormalities seen on magnetic resonance imaging of the brain in patients receiving anti-amyloid immunotherapy for Alzheimer disease.淀粉样蛋白相关影像学异常（ARIA）是接受抗淀粉样蛋白免疫治疗的阿尔茨海默病患者脑磁共振成像上见到的特征性异常。

Two forms are recognised, ARIA-E with vasogenic oedema or sulcal effusion and ARIA-H with microhaemorrhage or superficial siderosis, and both may be asymptomatic or clinically severe.目前识别两种类型，即伴血管源性水肿或脑沟积液的 ARIA-E 与伴微出血或表面含铁血黄素沉积的 ARIA-H，二者均可无症状，也可临床表现严重。

Terminology and classification

• The acronym ARIA stands for amyloid-related imaging abnormalities, and it was adopted to replace the earlier and narrower terms vasogenic oedema and amyloid-related imaging abnormality.缩写 ARIA 代表淀粉样蛋白相关影像学异常，用以取代较早且较狭窄的血管源性水肿与淀粉样蛋白相关影像学异常等称谓。
• ARIA-E denotes effusion or oedema, in which fluid accumulates in the brain parenchyma or sulci because the blood-brain barrier becomes leaky.ARIA-E 指积液或水肿，因血脑屏障通透性增高致使液体在脑实质或脑沟内积聚。
• ARIA-H denotes haemorrhage, encompassing new cerebral microhaemorrhages and superficial siderosis, and it may occur with or without ARIA-E.ARIA-H 指出血，涵盖新发脑微出血与表面含铁血黄素沉积，可伴或不伴 ARIA-E。
• ARIA is a radiological construct rather than a clinical syndrome, so the same imaging pattern may be silent in one patient and cause encephalopathy in another.ARIA 属于影像学构念而非临床综合征，因此同一影像表现可在某些患者中静默，而在另一些患者中引起脑病。
• Severity is graded from mild to severe according to the extent of FLAIR hyperintensity for ARIA-E and the number of new microhaemorrhages or foci of superficial siderosis for ARIA-H.严重程度按 ARIA-E 的 FLAIR 高信号范围、以及 ARIA-H 的新发微出血或表面含铁血黄素沉积灶数目，分为轻、中、重度。
• In the International Classification of Diseases the finding is indexed under R93.0 for abnormal findings on diagnostic imaging of the skull and head, and ICD-11 places it in the corresponding imaging-finding category ME90.在国际疾病分类中，该所见归入颅脑影像学异常发现的 R93.0，ICD-11 将其置于相应的影像学发现类目 ME90。

History

• ARIA was first recognised during phase 2 and phase 3 trials of bapineuzumab, when unexpected FLAIR hyperintensity and microhaemorrhages appeared in treated patients.ARIA 最早在巴匹奈单抗（bapineuzumab）的二期与三期试验中被识别，当时治疗组患者出现意料之外的 FLAIR 高信号与微出血。
• A pooled analysis of the bapineuzumab phase 3 studies published in 2018 characterised the clinical and radiological spectrum of ARIA and its association with APOE genotype.2018 年发表的巴匹奈单抗（bapineuzumab）三期研究汇总分析刻画了 ARIA 的临床与影像谱及其与 APOE 基因型的关联。^[1]
• The Alzheimer's Association Research Roundtable Workgroup published consensus recommendations in 2011 that standardised the definitions, severity grading and monitoring of ARIA.阿尔茨海默病协会研究圆桌工作组于 2011 年发表共识建议，统一了 ARIA 的定义、严重程度分级与监测方案。^[2]
• The aducanumab phase 3 programme, reported in 2022, showed that ARIA was the principal safety concern of high-dose anti-amyloid antibody therapy.2022 年报告的阿杜那单抗（aducanumab）三期项目显示，ARIA 是高剂量抗淀粉样蛋白抗体治疗的主要安全性问题。^[3]
• Aducanumab received accelerated approval in 2021 and its manufacturer announced discontinuation in 2024, in part because uptake was limited by uncertainty about benefit and by ARIA monitoring requirements.阿杜那单抗（aducanumab）于 2021 年获加速批准，其生产商于 2024 年宣布停产，部分原因是对获益的不确定与 ARIA 监测要求限制了使用。
• Lecanemab was reported in 2023 to slow cognitive decline in early Alzheimer disease and received traditional approval, with ARIA occurring in a substantial minority of treated patients.2023 年报告仑卡奈单抗（lecanemab）可减缓早期阿尔茨海默病的认知衰退并获传统批准，相当比例的治疗患者出现 ARIA。^[4]
• Donanemab was reported in 2023 and approved in 2024, and its trial confirmed the same ARIA spectrum with a higher frequency of ARIA-H than lecanemab.多奈单抗（donanemab）于 2023 年报告并于 2024 年获批，其试验确认了相同的 ARIA 谱，且 ARIA-H 频率高于仑卡奈单抗（lecanemab）。^[5]
• An update from the Alzheimer's Association ARIA workgroup in 2026 consolidated monitoring, risk stratification and management recommendations across the newer agents.2026 年阿尔茨海默病协会 ARIA 工作组的更新整合了较新药物的监测、风险分层与管理建议。^[6]

Epidemiology

• The frequency of ARIA depends on the antibody, the dose, the baseline amyloid burden and above all on APOE genotype, so figures from different trials are not directly comparable.ARIA 的发生频率取决于抗体种类、剂量、基线淀粉样负荷，尤其是 APOE 基因型，因此不同试验的数字不能直接比较。
• In the lecanemab phase 3 trial ARIA-E occurred in 12.6 per cent and ARIA-H in 17.3 per cent of treated patients, while symptomatic ARIA-E occurred in 2.8 per cent.在仑卡奈单抗（lecanemab）三期试验中，治疗患者 ARIA-E 发生率为 12.6%、ARIA-H 为 17.3%，而有症状的 ARIA-E 为 2.8%。^[4]
• In the donanemab phase 3 trial ARIA-E occurred in 24.0 per cent and ARIA-H in 31.4 per cent, with symptomatic ARIA in about 6 per cent.在多奈单抗（donanemab）三期试验中，ARIA-E 发生率为 24.0%、ARIA-H 为 31.4%，有症状的 ARIA 约 6%。^[5]
• Aducanumab at 10 milligrams per kilogram produced ARIA-E in roughly one third of patients in the phase 3 programme, a higher rate than the newer antibodies.阿杜那单抗（aducanumab）在 10 毫克每千克剂量下使三期项目中约三分之一患者出现 ARIA-E，发生率高于较新的抗体。^[3]
• APOE ε4 homozygotes carry the highest risk, with ARIA-E in about 32.6 per cent of lecanemab-treated homozygotes and about 43 per cent of donanemab-treated homozygotes.APOE ε4 纯合子风险最高，仑卡奈单抗（lecanemab）治疗的纯合子 ARIA-E 约 32.6%，多奈单抗（donanemab）治疗的纯合子约 43%。
• Most ARIA is asymptomatic and detected only by protocol magnetic resonance imaging, and serious events such as severe encephalopathy or fatal haemorrhage are uncommon.多数 ARIA 无症状，仅在方案规定的磁共振检查中被发现，严重脑病或致死性出血等严重事件并不常见。
• Cerebral microhaemorrhages are present in about 6 per cent of healthy elderly people and in 50 to 80 per cent of those with cerebrovascular disease, which complicates attribution to treatment.脑微出血在健康老年人中约占 6%，在脑血管病患者中占 50% 至 80%，这使归因于治疗变得复杂。

Pathophysiology

• Anti-amyloid antibodies bind amyloid deposited in the walls of leptomeningeal and cortical vessels, and this vascular target is the substrate for ARIA.抗淀粉样蛋白抗体结合沉积于软脑膜与皮质血管壁的淀粉样蛋白，这一血管靶点是 ARIA 的基础。
• Binding triggers local inflammation and loss of tight endothelial junctions, so the blood-brain barrier becomes permeable and protein-rich fluid leaks into the parenchyma and sulci.结合触发局部炎症与内皮紧密连接丧失，使血脑屏障通透性增高，富含蛋白的液体漏入脑实质与脑沟。
• This leak produces the FLAIR hyperintensity and sulcal effusion that define ARIA-E, and the abnormality is usually reversible when the antibody is withheld.这一渗漏造成定义 ARIA-E 的 FLAIR 高信号与脑沟积液，停用抗体后该异常通常可逆。
• As amyloid is cleared from vessel walls, the vessel becomes weaker and more fragile, predisposing to microhaemorrhage and to superficial siderosis, which define ARIA-H.随着血管壁淀粉样蛋白被清除，血管变弱变脆，易发生微出血与表面含铁血黄素沉积，从而构成 ARIA-H。
• Cerebral amyloid angiopathy is therefore the key pathological substrate, and patients with severe amyloid angiopathy have the highest risk of haemorrhagic ARIA.因此脑淀粉样血管病是关键病理基础，严重淀粉样血管病患者出血性 ARIA 风险最高。
• APOE ε4 promotes amyloid deposition in vessel walls and impairs clearance, which explains the steep gene-dose effect on ARIA frequency and severity.APOE ε4 促进淀粉样蛋白在血管壁沉积并损害清除，这解释了其对 ARIA 频率与严重程度的陡峭基因剂量效应。
• An immune-inflammatory component is supported by the presence of perivascular inflammatory cells and by the occasional response to corticosteroids in severe cases.血管周围炎症细胞的存在以及严重病例偶尔对糖皮质激素有反应，支持存在免疫炎症成分。
• ARIA-E and ARIA-H can occur independently, and some patients develop only microhaemorrhages without any detectable oedema.ARIA-E 与 ARIA-H 可独立发生，部分患者仅出现微出血而无可见水肿。

Clinical features

• Most patients are asymptomatic, and ARIA is discovered only because magnetic resonance imaging is performed on a scheduled basis during treatment.多数患者无症状，ARIA 仅因治疗期间按计划行磁共振检查而被发现。
• Symptomatic ARIA-E typically causes headache, nausea, vomiting, dizziness, confusion, gait disturbance and focal neurological deficits.有症状的 ARIA-E 典型表现为头痛、恶心、呕吐、头晕、意识模糊、步态障碍与局灶性神经功能缺损。
• Severe ARIA-E can produce encephalopathy, seizures, status epilepticus, raised intracranial pressure and, rarely, death.严重 ARIA-E 可引起脑病、癫痫、癫痫持续状态、颅内压升高，罕见情况下致死。
• ARIA-H is usually silent, but superficial siderosis may cause focal deficits, and extensive haemorrhage can present with acute neurological deterioration.ARIA-H 通常静默，但表面含铁血黄素沉积可引起局灶性缺损，广泛出血可表现为急性神经功能恶化。
• ARIA occurs most often during the first months of treatment and after dose escalation, but late events have been reported and monitoring must continue.ARIA 最常发生于治疗最初数月及剂量递增后，但已有晚期事件报告，监测须持续。
• Rechallenge after ARIA carries a risk of recurrence, and the decision requires weighing radiological severity against expected clinical benefit.ARIA 后重新用药存在复发风险，决策须权衡影像学严重程度与预期临床获益。
• Older and frail patients may present atypically with falls, delirium or functional decline rather than with focal symptoms.高龄与衰弱患者可能以跌倒、谵妄或功能下降等非典型方式起病，而非局灶症状。

Diagnosis

• Diagnosis rests on magnetic resonance imaging with FLAIR for oedema, T2-star or susceptibility-weighted sequences for haemorrhage, and comparison with the baseline scan.诊断依赖磁共振成像：FLAIR 序列评估水肿，T2* 或磁敏感加权序列评估出血，并与基线扫描比较。
• ARIA-E appears as FLAIR hyperintensity confined to one sulcus or to cortex and subcortical white matter, and severity is graded by the extent of involvement.ARIA-E 表现为局限于单一脑沟或皮质与皮质下白质的 FLAIR 高信号，严重程度按受累范围分级。
• ARIA-H appears as new round low-signal lesions of up to 10 millimetres on T2-star or as linear hypointensity along the cortical surface indicating superficial siderosis.ARIA-H 表现为 T2* 上直径至多 10 毫米的新发圆形低信号灶，或沿皮质表面的线状低信号，提示表面含铁血黄素沉积。
• The differential includes ischaemic stroke, posterior reversible encephalopathy syndrome, cerebral venous thrombosis, infection, tumour and cerebral amyloid angiopathy-related inflammation.鉴别诊断包括缺血性卒中、可逆性后部脑病综合征、脑静脉血栓形成、感染、肿瘤与脑淀粉样血管病相关炎症。
• Baseline magnetic resonance imaging should document microhaemorrhage count, superficial siderosis and white matter lesions, because these modify the risk of ARIA.基线磁共振应记录微出血数目、表面含铁血黄素沉积与白质病变，因为这些改变影响 ARIA 风险。
• APOE genotyping is recommended before treatment because homozygotes have a much higher risk and may require more intensive monitoring or a different risk discussion.建议治疗前进行 APOE 基因分型，因为纯合子风险显著更高，可能需要更密集监测或不同的风险沟通。
• Monitoring schedules specified in the product labels include scans before treatment and at defined intervals during the first year, with additional imaging whenever symptoms occur.产品说明书规定的监测方案包括治疗前及第一年内规定间隔的扫描，出现症状时随时加做影像检查。

Management

• Management depends on radiological severity and on whether symptoms are present, and the antibody is continued, withheld or permanently stopped accordingly.处理取决于影像学严重程度与有无症状，据此继续用药、暂停用药或永久停药。
• Mild asymptomatic ARIA-E may allow continued dosing with close radiological follow-up, provided the patient and family are warned about new symptoms.轻度无症状 ARIA-E 可在密切影像随访下继续给药，但须告知患者与家属警惕新发症状。
• Moderate ARIA-E usually requires withholding the antibody until the imaging abnormality resolves, after which treatment may be resumed with caution.中度 ARIA-E 通常需暂停抗体直至影像异常消退，之后可谨慎恢复治疗。
• Severe ARIA-E, symptomatic ARIA with seizures, or extensive ARIA-H generally leads to permanent discontinuation of the drug.重度 ARIA-E、伴癫痫的有症状 ARIA 或广泛 ARIA-H 通常导致永久停药。
• Corticosteroids are not routinely recommended for ARIA, although they are sometimes used in severe inflammatory cases on an individual basis.糖皮质激素不作为 ARIA 的常规推荐，尽管严重炎症病例有时个体化使用。
• Seizures require anticonvulsant treatment, and raised intracranial pressure or status epilepticus requires intensive care and neurocritical support.癫痫需抗癫痫药物治疗，颅内压升高或癫痫持续状态需重症监护与神经重症支持。
• Anticoagulant and antiplatelet therapy should be reviewed during ARIA, because these drugs increase the risk of haemorrhagic progression.ARIA 期间应复核抗凝与抗血小板治疗，因为这些药物增加出血进展的风险。
• Patients and families should receive written information about ARIA symptoms, the monitoring schedule and when to seek urgent assessment.应向患者与家属提供关于 ARIA 症状、监测安排及何时寻求急诊评估的书面信息。

Research and controversies

• Plasma biomarkers such as glial fibrillary acidic protein and neurofilament light are being studied as early indicators of ARIA, but none has replaced magnetic resonance imaging.血浆胶质纤维酸性蛋白与神经丝轻链等生物标志物正被研究作为 ARIA 的早期指标，但尚无一项取代磁共振成像。
• The safety of rechallenge after an episode of ARIA is uncertain, and the few reported series are too small to define selection criteria.ARIA 发作后重新用药的安全性尚不确定，已报告的少量系列样本过小，无法确定选择标准。
• Whether asymptomatic ARIA causes lasting cognitive or structural injury is unresolved, and long-term imaging and neuropsychological follow-up studies are ongoing.无症状 ARIA 是否造成持久认知或结构损伤尚未明确，长期影像与神经心理随访研究正在进行。
• Real-world ARIA rates may differ from trial rates because trial populations exclude patients with extensive microhaemorrhage, advanced cerebral amyloid angiopathy and anticoagulation.真实世界 ARIA 发生率可能与试验不同，因为试验人群排除了广泛微出血、晚期脑淀粉样血管病与抗凝治疗者。
• Harmonising ARIA definitions and monitoring across agents and regulators remains a priority, because differences in grading hinder comparison of safety data.在药物与监管机构之间统一 ARIA 定义与监测仍是优先事项，因为分级差异妨碍安全性数据比较。
• Whether ARIA reflects effective amyloid clearance and predicts clinical benefit is debated, and imaging-pathology correlation studies are needed to settle the question.ARIA 是否反映有效的淀粉样清除并预示临床获益仍有争议，需影像与病理对照研究来解答。