What is Leqembi (Lecanemab)?
Leqembi, with the generic name lecanemab, is an FDA-approved prescription medication used to treat adults with early-stage Alzheimer's disease [1.3.5]. It's administered as an intravenous (IV) infusion every two weeks [1.3.3]. Leqembi is a monoclonal antibody designed to target and remove aggregated forms of beta-amyloid, a protein that forms plaques in the brains of people with Alzheimer's disease [1.3.5, 1.3.6]. By reducing these plaques, the medication has been shown to slow the rate of cognitive and functional decline in patients with mild cognitive impairment or mild dementia stage of the disease [1.3.5, 1.6.5].
Can Leqembi Cause Confusion? The Direct Answer
Yes, Leqembi can cause confusion [1.2.6, 1.2.7]. Confusion is listed as a potential symptom of one of the most significant risks associated with the drug: Amyloid-Related Imaging Abnormalities, commonly known as ARIA [1.3.2, 1.5.3]. While many side effects of Leqembi are mild, such as infusion-related reactions or headaches, the potential for neurological symptoms like confusion requires careful consideration and monitoring [1.3.4]. In the Clarity AD clinical trial, symptomatic ARIA occurred in about 3% of patients, with confusion being one of the reported symptoms [1.4.2]. It is crucial for patients and caregivers to be vigilant and report any new or worsening confusion to their healthcare provider immediately [1.7.2].
Understanding Amyloid-Related Imaging Abnormalities (ARIA)
ARIA is a critical side effect to understand when considering treatment with Leqembi and other anti-amyloid therapies. It is detected via magnetic resonance imaging (MRI) scans and has a boxed warning from the FDA due to its potential severity [1.3.4, 1.3.6]. ARIA is categorized into two types:
- ARIA-E (Edema): This refers to cerebral edema or sulcal effusions, which is essentially swelling in the brain caused by fluid leakage from blood vessels [1.4.6, 1.5.7]. While often asymptomatic, when symptoms do occur, they can include headache, dizziness, vision changes, nausea, difficulty walking, and confusion [1.2.3, 1.3.2]. In the main Leqembi trial, ARIA-E was observed in 12.6% of treated patients, compared to just 1.7% in the placebo group [1.4.6].
- ARIA-H (Hemosiderin Deposition): This involves microhemorrhages (small spots of bleeding) or superficial siderosis (bleeding on the surface of the brain) [1.3.6]. ARIA-H was seen in 17.3% of Leqembi patients versus 9.0% of placebo patients in clinical trials [1.4.6]. Like ARIA-E, it is often asymptomatic, but larger hemorrhages can occur and be life-threatening [1.3.1, 1.5.5].
Most cases of ARIA occur early in treatment, typically within the first 14 weeks [1.3.7].
Risk Factors and Mandatory Patient Monitoring
The risk of developing ARIA is not the same for all patients. A significant risk factor is a person's genetic makeup, specifically their Apolipoprotein E ε4 (ApoE ε4) gene status [1.4.4]. Patients who are ApoE ε4 homozygotes (carrying two copies of the gene) have a substantially higher incidence of ARIA, including symptomatic and severe cases, compared to those with one copy (heterozygotes) or no copies (noncarriers) [1.4.7]. Because of this, the FDA recommends ApoE ε4 genetic testing before starting Leqembi to inform the risk-benefit discussion between doctor and patient [1.4.4, 1.7.1].
Due to the risks of ARIA, strict monitoring is a required part of Leqembi treatment. The FDA recommends a baseline MRI scan before starting the drug, followed by surveillance MRIs before the 3rd, 5th, 7th, and 14th infusions [1.7.2, 1.7.3]. This monitoring is crucial for detecting ARIA early, as it is often asymptomatic [1.7.1]. If ARIA is detected, a healthcare provider may decide to temporarily suspend or permanently stop treatment depending on its severity [1.7.1].
Comparison of Common Side Effects: Leqembi vs. Aduhelm
Leqembi is often compared to Aduhelm (aducanumab), another anti-amyloid antibody for Alzheimer's. While both carry risks of ARIA, clinical data suggests different safety profiles.
| Side Effect / Feature | Leqembi (lecanemab) | Aduhelm (aducanumab) |
|---|---|---|
| Incidence of ARIA-E | Approx. 12.6% [1.4.6] | Approx. 35% [1.6.3] |
| Incidence of ARIA-H | Approx. 17.3% [1.4.6] | Approx. 19-34% [1.5.2, 1.6.3] |
| Symptomatic ARIA | Approx. 3% [1.4.2] | Higher incidence reported (up to 26% of ARIA cases) [1.6.2] |
| Infusion Reactions | Approx. 26% [1.4.2] | Less commonly reported than Leqembi [1.6.2] |
Conclusion: Balancing Benefits and Risks
The potential for Leqembi to cause confusion is a real and documented risk, intrinsically linked to the development of ARIA. While the medication offers a statistically significant benefit in slowing cognitive decline for those in the early stages of Alzheimer's disease, this benefit must be carefully weighed against its serious potential side effects [1.6.5, 1.6.6]. The decision to begin treatment with Leqembi is a complex one that requires a thorough discussion with a neurologist, genetic testing for ApoE ε4 status, and a commitment to the rigorous MRI monitoring schedule [1.7.1]. For patients and their families, understanding the signs of ARIA, especially confusion, headache, or dizziness, is paramount for ensuring safety during treatment [1.7.2].
For authoritative information, please consult the official LEQEMBI® Prescribing Information. [1.3.6]
