Neurologic Imaging

Which Imaging Is Best Before Starting Anti-Amyloid Therapy for Alzheimer’s Disease?

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Which Imaging Is Best Before Starting Anti-Amyloid Therapy for Alzheimer's Disease?

A 74-year-old man with a confirmed diagnosis of mild Alzheimer disease sits with his family in your neurology clinic. After a thorough discussion of risks and benefits, they are hopeful about starting treatment with a new anti-amyloid monoclonal antibody. You agree he is a good candidate, but before writing the first infusion order, you must obtain baseline imaging to screen for pre-existing conditions that could increase his risk of serious side effects. The question is no longer about diagnosing Alzheimer’s, but about ensuring safety before initiating a powerful new therapy. What is the correct imaging study to order?

This article provides a detailed clinical workflow for the specific scenario of pretreatment imaging in an adult with known Alzheimer disease who is being considered for anti-amyloid monoclonal antibody therapy. According to the American College of Radiology (ACR) Appropriateness Criteria, the recommended study is MRI head without IV contrast, which is rated Usually Appropriate.

Who Fits This Clinical Scenario for Pretreatment Alzheimer’s Imaging?

This guidance is narrowly focused on a specific patient population at a distinct point in their care journey. The recommendations apply to adults with a previously established diagnosis of Alzheimer disease (AD), typically in the mild cognitive impairment or mild dementia stage, who are candidates for and are actively considering therapy with an anti-amyloid monoclonal antibody.

The primary purpose of imaging in this context is not diagnosis, but safety screening and establishing a baseline before treatment begins.

This workflow does not apply to patients in the following situations:

  • Initial Diagnostic Workup: If a patient presents with cognitive impairment and you suspect Alzheimer disease but a diagnosis has not yet been confirmed, that represents an initial workup. This would fall under a different clinical scenario, such as Adult. Cognitive impairment with memory deficits. Suspect Alzheimer disease with typical clinical presentation. Initial imaging.
  • Post-Treatment Monitoring: This article covers pretreatment imaging only. Patients who are already receiving anti-amyloid therapy require routine monitoring scans to surveil for treatment-related complications. That workflow is covered in the sibling scenario, Adult. Known Alzheimer disease undergoing therapy with anti-amyloid monoclonal antibodies. Posttreatment imaging.
  • Atypical Presentations: If the patient’s symptoms suggest an alternative diagnosis, such as frontotemporal dementia (behavioral changes) or dementia with Lewy bodies (visual hallucinations, parkinsonism), the initial imaging strategy would be different.

What Are You Screening for With Pretreatment Imaging?

In this scenario, the imaging goal shifts from diagnosis to risk stratification. The “differential” is less about identifying the cause of dementia (which is already known) and more about detecting pre-existing pathologies that could contraindicate or elevate the risks associated with anti-amyloid therapies.

Amyloid-Related Imaging Abnormalities (ARIA): The most significant concern with anti-amyloid monoclonal antibodies is the risk of ARIA. This can manifest as ARIA-E (vasogenic edema or sulcal effusions) or ARIA-H (hemosiderin deposition, including microhemorrhages and superficial siderosis). While ARIA is a treatment-emergent side effect, the presence of significant pre-existing microhemorrhages or any superficial siderosis dramatically increases the risk of developing severe, symptomatic ARIA during therapy. The baseline scan is essential for quantifying this pre-existing burden.

Cerebral Amyloid Angiopathy (CAA): This condition, where amyloid-β protein deposits in the walls of cerebral arteries, is a common co-pathology in Alzheimer disease. It is the primary underlying cause of the microhemorrhages and superficial siderosis seen in these patients. Identifying evidence of moderate to severe CAA on baseline imaging is a critical part of the safety assessment, as these patients are at the highest risk for treatment-related intracranial hemorrhage.

Exclusionary Structural Lesions: Less commonly, the pretreatment scan serves as a final safety check to rule out other significant intracranial pathologies that might have been missed or developed since the last imaging study. This includes brain tumors, evidence of prior large hemorrhages, vascular malformations, or extensive white matter disease from other causes. The presence of such a lesion could independently increase the risk of neurologic complications or might be a contraindication to therapy.

Why Is MRI Head without Contrast the Recommended Pretreatment Study?

The ACR designates MRI head without IV contrast as Usually Appropriate because it is uniquely capable of identifying the key risk factors for ARIA with high sensitivity and without exposing the patient to ionizing radiation or intravenous contrast agents.

The rationale for this recommendation is rooted in the specific sequences an MRI can perform. To properly screen for ARIA risk, the MRI protocol must include a blood-sensitive sequence like Susceptibility-Weighted Imaging (SWI) or a T2* Gradient Recalled Echo (GRE) sequence. These sequences are exceptionally sensitive for detecting the tiny magnetic susceptibility artifacts caused by hemosiderin, the iron-containing remnant of old blood. This allows for the clear visualization and quantification of chronic microhemorrhages and superficial siderosis, which are the most critical findings for pretreatment risk assessment.

Let’s examine why alternative studies are rated lower for this specific task:

  • CT head without IV contrast is rated Usually not appropriate. While excellent for detecting acute, large-scale hemorrhage, noncontrast CT is profoundly insensitive to chronic microhemorrhages and superficial siderosis. Ordering a CT for this purpose would provide false reassurance, as it is incapable of detecting the primary imaging biomarkers that predict high ARIA risk.
  • MRI head without and with IV contrast is also rated Usually not appropriate. The administration of gadolinium-based contrast adds no value to the primary goal of screening for pre-existing hemorrhage. It does not improve the detection of microhemorrhages or siderosis. Therefore, it introduces unnecessary cost, scan time, and the potential for contrast-related adverse events without providing clinically useful information for this specific decision.

From a safety and practical standpoint, MRI is the ideal choice. It uses no ionizing radiation (0 mSv), a significant benefit for patients who will require multiple follow-up scans throughout their treatment course. By contrast, a CT head study involves a radiation dose of 1-10 mSv. When ordering the study, it is crucial to communicate the clinical indication clearly. A request for “MRI Brain for ARIA screening” or “MRI Brain, include SWI or GRE sequence for microhemorrhage evaluation” ensures the radiology department performs the correct protocol.

What’s Next After MRI Head without IV Contrast? Downstream Workflow

The results of the baseline MRI directly inform the decision to proceed with anti-amyloid therapy and guide the subsequent monitoring plan. The workflow branches based on the presence and burden of pre-existing hemorrhage.

  • If the MRI is negative (0 microhemorrhages and no superficial siderosis): The patient meets the imaging safety criteria to initiate therapy. This finding is associated with the lowest risk of developing severe ARIA. The standard monitoring protocol, as outlined in the drug’s prescribing information (typically with additional MRIs before certain infusion milestones), can be followed.
  • If the MRI shows a low burden of microhemorrhages (e.g., 1 to 4): Most clinical trials for anti-amyloid agents allowed for the inclusion of patients with up to four pre-existing microhemorrhages. In this case, therapy may still be initiated, but it requires a careful and explicit discussion with the patient and their family about the elevated risk of ARIA. Some clinicians may opt for a more frequent imaging surveillance schedule in these patients.
  • If the MRI shows a high burden of microhemorrhages (>4) or any evidence of superficial siderosis: This is a major red flag. The presence of more than four microhemorrhages, and particularly the finding of superficial siderosis, is a strong predictor of severe, symptomatic, and sometimes life-threatening ARIA. In most clinical trials, these findings were an exclusion criterion. Initiating therapy in such a patient is generally contraindicated and represents a significant safety risk.
  • If the MRI reveals an unexpected finding (e.g., a mass, large territorial infarct): The plan to start anti-amyloid therapy should be paused immediately. The new finding takes precedence and requires a separate diagnostic workup. The Alzheimer’s treatment plan can only be revisited after the new pathology has been fully evaluated and managed.

Pitfalls to Avoid (and When to Get Help)

Navigating pretreatment imaging for anti-amyloid therapy requires careful attention to detail. Here are common pitfalls to avoid:

  • Ordering CT Instead of MRI: This is the most critical error. A negative head CT does not rule out the risk factors for ARIA. Only a properly protocoled MRI can provide the necessary safety information.
  • Accepting an Incomplete MRI: A standard “MRI Brain” may not automatically include the necessary SWI or GRE sequences. Always confirm that a blood-sensitive sequence was performed and interpreted. If not, the study is incomplete for this indication.
  • Underestimating the Significance of Superficial Siderosis: While microhemorrhages are counted, the presence of any superficial siderosis is often a more ominous sign of advanced CAA and confers a very high risk of future hemorrhage.
  • Ignoring ApoE4 Status: While not an imaging finding, the patient’s Apolipoprotein E ε4 (ApoE4) genotype is a powerful independent risk factor for ARIA. The imaging findings should always be interpreted in the context of the patient’s genetic risk.

If the MRI report is ambiguous about the number of microhemorrhages or the presence of siderosis, escalate by speaking directly with the interpreting neuroradiologist to clarify the findings before making a treatment decision.

Related ACR Topics and Tools

For further research and to explore adjacent clinical scenarios, the following GigHz resources are available:

Frequently Asked Questions

Why is amyloid PET/CT not the recommended first-line study for pretreatment screening?

While amyloid PET/CT is rated ‘Usually Appropriate’ and confirms the presence of amyloid plaques (often a requirement for treatment eligibility), it is not the primary study for safety screening. Amyloid PET does not provide the structural detail needed to detect microhemorrhages or superficial siderosis, which are the key risk factors for ARIA. An MRI is still required for safety screening even if an amyloid PET has been performed.

What specific MRI sequences must be included for ARIA screening?

The most critical sequence is one that is sensitive to blood products (hemosiderin). This is typically a Susceptibility-Weighted Imaging (SWI) or a T2* Gradient Recalled Echo (GRE) sequence. Standard sequences like T1, T2, and FLAIR are also necessary to assess for other structural abnormalities, but the SWI/GRE sequence is non-negotiable for this specific indication.

If a patient had a diagnostic MRI for Alzheimer’s a year ago, do I need a new one before starting therapy?

Yes. A new, baseline MRI is required immediately prior to starting therapy (typically within one year, per prescribing information). The purpose is to establish a current baseline, as microhemorrhages can accumulate over time. An older scan does not reflect the patient’s current risk profile.

Does the presence of white matter hyperintensities on FLAIR imaging affect the decision to start therapy?

A mild to moderate burden of chronic small vessel ischemic white matter disease is common in this age group and is not typically a contraindication to starting anti-amyloid therapy. However, extensive, confluent white matter changes may warrant additional consideration and a discussion with a neuroradiologist, as they can sometimes obscure or be confused with ARIA-E if it develops.

How does this pretreatment imaging differ from the routine monitoring imaging done during therapy?

Pretreatment imaging is a one-time scan to establish a baseline and screen for pre-existing contraindications like a high burden of microhemorrhages. Monitoring imaging is a series of MRIs performed at set intervals during treatment (e.g., before the 5th, 7th, and 14th infusions) with the specific goal of detecting new, treatment-emergent ARIA-E or ARIA-H, which may require pausing or discontinuing therapy.

Reviewed by Pouyan Golshani, MD, Interventional Radiologist — May 30, 2026