Amyloid-related imaging abnormalities (ARIA) refer to MRI-detected brain changes associated with anti-amyloid monoclonal antibody (mAb) treatments for Alzheimer’s disease (AD). ARIA was first defined in 2010 during trials of bapineuzumab, where some patients developed MRI evidence of edema and microhemorrhages².  ARIA is subdivided into ARIA-E (edema or effusion) and ARIA-H (hemosiderin-related abnormalities like microhemorrhages or superficial siderosis)^1,2. These findings are thought to result from therapy-induced vascular inflammation and leakage: as antibodies remove β-amyloid plaque, protein-rich fluid or blood products can leak from fragile cerebral Vessels². 

MRI can detect changes an inform decisions about appropriate medication management or cessation. Regular MRI surveillance is crucial because ARIA is a common adverse effect of amyloid-lowering therapy, often occurring early in treatment [MP2] ^1,2. Clinical trials and FDA guidelines indicate that most ARIA events happen within the first 8–12 doses (roughly the first 6 months) of therapy^1,2.  Risk factors include higher drug dose/exposure and patient APOE ε4 genotype (carriers have a higher incidence of ARIA). Many cases of ARIA are asymptomatic or cause only mild, non-localizing symptoms (e.g. headache, confusion) ^1,2.  However, because ARIA can occasionally be severe or life-threatening, MRI monitoring is an essential safety measure ^1,2. 

Donanemab (brand name Kisunla) became the first anti-amyloid monoclonal antibody approved by the TGA in September 2025 for early Alzheimer’s disease ^3,4.

Patients starting on monoclonal antibody treatment require a baseline brain MRI and periodic follow-up MRI scans to monitor for ARIA, therefore all I-MED MRI clinics will follow the appropriate protocols configured to allow for routine ARIA imaging. As of this writing, there are no separate RANZCR standards for ARIA; thus, we follow the American Journal of Neuroradiology (AJNR) consensus recommendations for protocol and reporting. In practice, this means performing baseline and periodic follow-up MRIs on all patients receiving anti-amyloid mAb therapy to detect ARIA before it progresses and to guide management.

Referrals should always note that the patient is on AD treatment to ensure appropriate imaging and reporting. 

Treatment Referrals for ARIA related imaging that are unclear as to which protocol (baseline/asymptomatic interval/symptomatic interval) is required, or non-specific referrals that may be for ARIA related imaging will be reviewed by reporting radiologists and clarification sought from the referring practitioner as per standard practice.

The AJNR recommended MRI protocol is a set of minimum required sequences tailored to detect subtle oedema and microhemorrhages associated with ARIA. These fixed/minimum sequences should be consistent across baseline and follow-up exams. All scans are to be performed without gadolinium contrast for baseline and routine asymptomatic ARIA monitoring, unless otherwise specified by a radiologist or local protocol. At the discretion of the reporting Radiologist, Gadolinium contrast may be indicated for symptomatic patients on anti-amyloid treatment to support differential diagnose. The fixed/minimum required sequences must always be performed, with additional sequences at the discretion of the reporting Radiologist, local system capabilities and local protocols. 

Imaging scheduling will be at the discretion of the referring/treating practitioner and will vary dependent on the specific therapy. The following represents an example of standard imaging schedule according to AJNR guidelines

a. Baseline/Enrollment

All patients should have a pretreatment MRI for ARIA assessment. The AJNR recommendations and FDA labeling require a recent MRI (ideally within the last year) before starting monoclonal antibody therapy1,2. In practice, a dedicated baseline MRI should be scheduled as close as possible to therapy initiation (often within a few weeks prior) to document any pre-existing microhemorrhages, siderosis, or edema. This MRI Protocols for ARIA Monitoring baseline exam serves as the reference for all future comparisons, so it must include the full ARIA protocol and be of high quality. If a patient’s most recent scan is older than 1 year or of inadequate composition (e.g. no GRE), it is recommended to obtain a new baseline exam prior to the first infusion^1,2.

b. Routine/Interval Monitoring

In the first year of anti-amyloid immunotherapy, it is recommended that patients undergo 3–4 routine non-contrast brain MRI scans to monitor for ARIA ^1,2. These scans focus on the initial 6 months of treatment as ARIA is infrequent after this period, however some drugs contain recommendations for additional scans at approximately week 52 post treatment commencement ². The specific timing of these scans may vary depending on the therapy used. According to FDA guidelines, lecanemab-treated patients should receive MRIs before the 5th, 7th, and 14th fortnightly infusions (with additional scan recommended before 26th infusion at week 52), while those receiving donanemab should be scanned prior to the 2nd, 3rd,4th, and 7th four-weekly infusions ^1,2.

*If ARIA is detected—whether or not symptoms are present—patients may undergo additional monthly MRI scans until ARIA-E resolves and ARIA-H stabilises.

c. Symptom Triggered Scans

Performed on an ad-hoc basis as neurologic symptoms present on an urgent or emergent basis. Due to the potential for stroke-like symptoms and the risk of thrombolytic treatment, AJNR recommend that “the radiologist should have increased vigilance when discussing findings on head CTs for patients on anti-amyloid immunotherapies and provide recommendations for further evaluation with MRI”. 

^{1. Cogswell PM, Andrews TJ, Barakos JA, Barkhof F, Bash S, Benayoun MD, Chiang GC, Franceschi AM, Jack CR Jr, Pillai JJ, Poussaint TY, Raji CA, Ramanan VK, Tanabe J, Tanenbaum L, Whitlow CT, Yu FF, Zaharchuk G, Zeinah M, Benzinger TS; ASNR Alzheimer, ARIA, and Dementia Study Group. Alzheimer Disease Anti-Amyloid Immunotherapies: Imaging Recommendations and Practice Considerations for Monitoring of Amyloid-Related Imaging Abnormalities. AJNR Am J Neuroradiol. 2025 Jan 8;46(1):24-32.}

^{2. Cogswell PM, Barakos JA, Barkhof F, Benzinger TS, Jack CR Jr, Poussaint TY, Raji CA, Ramanan VK, Whitlow CT. Amyloid-Related Imaging Abnormalities with Emerging Alzheimer Disease Therapeutics: Detection and Reporting Recommendations for Clinical Practice. AJNR Am J Neuroradiol. 2022 Sep;43(9): E19-E35.}

^{3. Therapeutic Goods Administration. Australian Public Assessment Report for Kisunla. May 2025}

^{4. Therapeutic Goods Administration. TGA's decision to not register lecanemab (LEQEMBI). Oct 2024}