The Link Between LEQEMBI and Stroke Risk: Can LEQEMBI Cause a Stroke?

October 10, 2025 •

4 min read

In clinical trials for the Alzheimer's medication LEQEMBI (lecanemab), up to 12.6% of patients experienced brain swelling (ARIA-E) and 17.3% experienced brain bleeding (ARIA-H), which was higher than in the placebo group. While often asymptomatic, these side effects can, in rare cases, manifest with serious, stroke-like symptoms or lead to fatal brain hemorrhages, raising concerns about if LEQEMBI can cause a stroke. The U.S. Food and Drug Administration (FDA) has issued a black box warning to highlight this significant safety risk.

Quick Summary

LEQEMBI can cause brain swelling and bleeding known as ARIA, which can present with stroke-like symptoms or, rarely, lead to a major hemorrhagic stroke, warranting close medical monitoring.

Key Points

Black Box Warning: LEQEMBI carries a black box warning from the FDA concerning the risk of Amyloid-Related Imaging Abnormalities (ARIA), which includes brain swelling and bleeding.
ARIA Can Mimic Stroke: Symptoms of ARIA, such as confusion and visual changes, can be stroke-like, and an acute brain hemorrhage is a rare but serious risk.
High-Risk Patient Groups: Individuals who are APOE ε4 carriers (especially homozygotes) or are taking anticoagulant medications are at a significantly higher risk of serious ARIA and brain bleeding.
Regular Monitoring is Essential: Patients on LEQEMBI must undergo routine MRI scans, particularly during the first year, to monitor for ARIA, which is often asymptomatic.
Emergency Protocols are Vital: If a patient on LEQEMBI has a suspected stroke, emergency medical staff must be immediately informed to avoid administering contraindicated medications like tPA.
Informed Decision-Making: The decision to take LEQEMBI must involve a careful and thorough discussion with a healthcare provider to weigh the modest clinical benefits against the serious potential risks.

What is LEQEMBI (Lecanemab)?

LEQEMBI is a monoclonal antibody treatment approved for patients in the early stages of Alzheimer's disease. It works by targeting and removing amyloid-beta (Aβ) protofibrils, which are believed to be toxic aggregates that contribute to the neurodegenerative process of Alzheimer's. By clearing these plaques from the brain, the medication aims to slow the progression of the disease. While this mechanism provides a new approach to treatment, it also introduces specific safety risks related to the way it interacts with vascular amyloid.

The Role of Amyloid-Related Imaging Abnormalities (ARIA)

The primary safety concern linking LEQEMBI to stroke risk is a phenomenon called Amyloid-Related Imaging Abnormalities, or ARIA. ARIA is detected via MRI scans and manifests in two forms:

ARIA-E (edema/effusion): This is characterized by temporary swelling or fluid accumulation in the brain. In clinical trials, ARIA-E typically occurred early in treatment and often resolved over time. While most cases are asymptomatic and mild, some patients may experience symptoms like headaches, confusion, dizziness, or visual disturbances. In severe cases, it can cause seizures or other serious neurological issues.
ARIA-H (hemorrhage/hemosiderin deposition): This involves microhemorrhages (small spots of bleeding) or superficial siderosis (iron deposits) on the surface of the brain. ARIA-H is more persistent and does not resolve in the same way as ARIA-E. The risk of ARIA-H is also higher with LEQEMBI compared to placebo.

How ARIA Can Mimic or Cause a Stroke

The connection between LEQEMBI and stroke is multifaceted. The symptoms of symptomatic ARIA, such as confusion, headaches, and difficulty walking, can closely resemble those of an ischemic stroke. This can complicate emergency treatment, as a large brain hemorrhage (ARIA-H) resulting from LEQEMBI treatment would make standard thrombolytic therapy for an ischemic stroke (e.g., tPA) extremely dangerous, potentially leading to fatal, multifocal brain hemorrhages. Case reports have confirmed the risk of fatal outcomes when thrombolytics are administered to patients on anti-amyloid therapy. Furthermore, the drug's mechanism of action, which involves disrupting vascular amyloid, can weaken blood vessels and directly increase the risk of a significant intracranial hemorrhage.

Key Risk Factors for ARIA and Intracerebral Hemorrhage

Several factors can increase a person's risk of developing ARIA and experiencing a stroke while on LEQEMBI. Pre-treatment evaluation is essential for assessing these risks.

APOE ε4 Genotype: Individuals who carry one or two copies of the APOE ε4 allele have a significantly higher risk of developing ARIA, particularly those who are homozygous (two copies). This higher risk is a critical consideration before beginning treatment.
Concomitant Anticoagulant Use: Patients taking anticoagulants or blood thinners (like warfarin, apixaban, or rivaroxaban) have an increased risk of severe brain bleeding if treated with LEQEMBI. Experts have recommended against combining these treatments until more data are available.
Pre-existing Cerebral Amyloid Angiopathy (CAA) or Microhemorrhages: Patients with signs of pre-existing CAA or a higher number of microhemorrhages at baseline are at an increased risk of ARIA-H with anti-amyloid therapies.

Comparison of LEQEMBI Risks and Management


Feature	LEQEMBI-Associated ARIA	Spontaneous Intracerebral Hemorrhage	Management Approach
Incidence	Higher rates of ARIA-H (17.3%) and ARIA-E (12.6%) observed in clinical trials compared to placebo.	Can occur spontaneously, with increasing risk in older adults with conditions like uncontrolled hypertension or CAA.	Close monitoring with routine MRI scans, especially during the first year of treatment.
Mechanism	Thought to result from the drug's effect on vascular amyloid, increasing vascular permeability.	Can be caused by various factors, including aneurysm rupture, cerebral amyloid angiopathy (CAA), or trauma.	Treatment requires a multidisciplinary team approach. Patients with symptomatic ARIA may need to pause or discontinue LEQEMBI infusions.
Risk Factors	Higher risk in ApoE ε4 carriers, especially homozygotes, and with concurrent use of anticoagulants.	Associated with older age, hypertension, and underlying cerebral vascular pathologies like CAA.	Genetic testing for ApoE ε4 status is recommended to inform risk discussions.
Potential Severity	Most ARIA is asymptomatic and mild, but severe and life-threatening events, including fatal hemorrhages, are possible, particularly with confounding factors.	Severity varies, but can lead to significant morbidity or mortality.	Urgent MRI evaluation is crucial for any new neurological symptoms to distinguish ARIA from an acute stroke.

Routine Monitoring for Safety

Due to the risks associated with ARIA, regular monitoring is a mandatory part of LEQEMBI treatment. The FDA-approved label specifies a schedule for MRI scans throughout the treatment course to detect asymptomatic ARIA. This allows healthcare providers to manage any changes early and determine whether a treatment pause or discontinuation is necessary. A registry for Alzheimer's treatment has also been encouraged to collect more real-world safety data.

What to Do in an Emergency

Patients receiving LEQEMBI are advised to carry information about their treatment. If stroke-like symptoms develop, it is critical to inform the emergency medical team that the patient is on an anti-amyloid therapy. This is because the approach to acute stroke treatment could be drastically different, and certain interventions could increase the risk of a fatal hemorrhage. A multidisciplinary team of specialists should be involved in the patient's care from the start to manage these complex scenarios.

Conclusion

While LEQEMBI offers a potential benefit by slowing the progression of early Alzheimer's, it carries a very real, though rare, risk of severe and potentially fatal brain hemorrhages via ARIA. It is crucial for patients and their families to understand the risks associated with this medication, especially the increased dangers for APOE ε4 carriers and those taking anticoagulants. Thorough pre-treatment screening, including genetic testing and baseline MRI, combined with careful monitoring throughout therapy, is essential for minimizing these serious risks. Patients must have open and honest discussions with their healthcare team to weigh the potential benefits against the potential harm before initiating and continuing this therapy.

For more detailed information, the prescribing information for LEQEMBI can be reviewed directly on the manufacturer's website.

Frequently Asked Questions

ARIA stands for Amyloid-Related Imaging Abnormalities, which are side effects seen on MRI scans of patients on anti-amyloid therapies like LEQEMBI. It can appear as brain swelling (ARIA-E) or small spots of brain bleeding (ARIA-H).

Most ARIA is asymptomatic. However, symptomatic cases can cause headaches, confusion, dizziness, vision changes, and seizures. Severe ARIA can cause life-threatening neurological events.

Patients carrying one or two copies of the APOE ε4 gene are at a higher risk of developing ARIA while on LEQEMBI. Individuals with two copies are at the greatest risk.

The use of anticoagulants (blood thinners) with LEQEMBI significantly increases the risk of serious brain bleeding. Most expert recommendations advise against combining these treatments.

If a patient on LEQEMBI suffers a stroke, emergency staff must be informed immediately. A different treatment protocol, avoiding certain potent blood thinners like tPA, may be necessary to prevent a potentially fatal brain hemorrhage.

Routine MRI monitoring is essential because it can detect ARIA even when the patient has no symptoms. This allows doctors to manage the condition early and potentially pause or adjust treatment to mitigate risk.

Major hemorrhagic stroke from LEQEMBI treatment is rare. However, the risk is elevated compared to placebo, and the potential for serious complications requires careful consideration, screening, and monitoring.