What is the significance of amyloid-related imaging abnormalities?

From the Guidelines

Amyloid-related imaging abnormality (ARIA) is a potential side effect that should be closely monitored in patients receiving certain Alzheimer's disease treatments, particularly monoclonal antibodies targeting amyloid plaques, with regular MRI scans and temporary suspension of medication if ARIA is detected. The use of amyloid PET imaging in clinical practice is guided by recommendations from the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association, which suggest that amyloid PET may be useful in patients with a cognitive complaint and confirmed impairment when Alzheimer's disease is in the differential but the diagnosis is uncertain 1. Key points to consider in the management of ARIA include:

• ARIA presents in two main forms: ARIA-E (edema) and ARIA-H (microhemorrhages)
• Treatment typically involves temporarily suspending the medication and monitoring with follow-up MRI scans
• Most cases resolve within 4-12 weeks
• For symptomatic patients with severe ARIA-E, corticosteroids may be prescribed, such as oral prednisone 40-60mg daily with a gradual taper over 1-2 weeks
• Regular MRI monitoring is recommended during treatment with anti-amyloid therapies, typically at baseline and after 3,6, and 12 months of treatment, as supported by studies such as the IDEAS study, which reported changes in medical management in 67.8% of MCI patients and 65.9% of dementia patients after amyloid PET 1. The AIT did not consider the potential impact on the AUC of the use of quantitative PET data, i.e., data from automated numerical measurements of specific ligand binding, due to insufficient published data 1. Risk factors for ARIA include APOE ε4 gene carriers, higher treatment doses, and pre-existing microhemorrhages, highlighting the importance of careful patient selection and monitoring 1. In clinical practice, the diagnosis of dementing diseases has implications that resonate beyond the patient to include family members, particularly those who are genetically related, and amyloid PET imaging does not substitute for a careful history and examination, but rather is one tool among many that clinicians should use judiciously to manage patients 1.

From the Research

Amyloid-Related Imaging Abnormalities

• Amyloid-related imaging abnormalities (ARIA) are a potential adverse effect of anti-amyloid immunotherapy, which can manifest as regions of edema or effusions (ARIA-E) or hemorrhagic lesions (ARIA-H) in the brain 2, 3.
• ARIA-E is characterized by transient, treatment-induced edema or sulcal effusion, identified on T2-FLAIR MRI, while ARIA-H is characterized by treatment-induced microhemorrhages or superficial siderosis, identified on T2* gradient recalled-echo MRI 2.
• The majority of ARIA occurrences are associated with mild or no clinical symptoms, but approximately 5% of ARIA events can be severe enough to result in hospitalization, permanent disability, or death 3.

Detection and Reporting of ARIA

• Standardized imaging protocols and rigorous reporting standards are essential for detecting and monitoring ARIA in clinical trials and clinical practice 2, 4.
• A standardized imaging protocol should include T2-FLAIR and T2* gradient recalled-echo MRI sequences to detect ARIA-E and ARIA-H, respectively 2.
• Radiologists should be familiar with the imaging appearance of ARIA and report findings using a standardized template to ensure accurate and consistent detection and monitoring of ARIA 2.

Risk Factors and Predictors of ARIA

• Apolipoprotein E haplotype and treatment dosage are major risk factors for ARIA-E and ARIA-H 4.
• Presence of any microhemorrhage on baseline MRI increases the risk of ARIA 4.
• Other risk factors and predictors of ARIA include age, sex, and presence of cerebral amyloid angiopathy 3, 4.

Management and Care of ARIA

• Management of ARIA requires a multidisciplinary approach, including proper clinical diagnosis, complication surveillance, specific imaging protocols, expert specialty consultation, integrated treatment strategies, and proper facility system planning 5.
• Recognition of treatment high-risk, high-benefit groups, and the interface of concurrent antiplatelet and anticoagulation is crucial for optimal care 5.
• Improved awareness and understanding of amyloid-modifying therapy, both benefits and potential complications, among the healthcare provider continuum is essential for providing high-quality patient care 5.