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Lecanemab vs Donanemab: How They Differ for Early Alzheimer's

If your loved one has been diagnosed with early Alzheimer's, you may have heard about two new medications called lecanemab and donanemab. These are not like older memory drugs that just manage symptoms—they actually target the underlying amyloid protein in the brain and can modestly slow cognitive decline. While neither is a cure, knowing how they differ can help you have a more informed conversation with your loved one's doctor. This article breaks down what makes each unique, including how they work, their effectiveness, safety profiles, and practical considerations for families.

Key points

  • Lecanemab and donanemab are anti-amyloid drugs for early Alzheimer's only—they are not for moderate or advanced stages.
  • Lecanemab targets smaller amyloid clumps before they form plaques; donanemab removes existing plaques.
  • Both modestly slow cognitive decline (27% and 35% in trials), but are not cures and do not work for everyone.
  • Both carry a risk of ARIA (brain swelling/bleeding) requiring regular MRI monitoring.
  • Treatment involves regular IV infusions—every 2 weeks for lecanemab, every 4 weeks for donanemab.
  • Patients can continue their current memory medications (like donepezil) while on these new drugs.
  • Preliminary real-world data suggests comparable safety and effectiveness to clinical trials, with high patient satisfaction.

What Are Lecanemab and Donanemab?

Both lecanemab and donanemab are anti-amyloid medications approved by the FDA for people in the earliest stages of Alzheimer's disease. They are the first treatments in over two decades that actually modify the disease process rather than just temporarily improving symptoms. Think of them as a new class of drugs that target the sticky amyloid plaques that build up in the brain during Alzheimer's. They are not appropriate for moderate or advanced stages, and they are not a cure—but for some people, they can slow the rate of cognitive decline by about 27% to 35% compared to placebo, based on clinical trial data.

How Do They Work Differently?

The key difference lies in what part of the amyloid process they target. Lecanemab works by binding to smaller, soluble clumps of amyloid (called protofibrils) before they form into full plaques. It essentially prevents the 'tumbleweed' from forming. Donanemab, on the other hand, targets fully formed amyloid plaques and helps the immune system clear them away. Both aim to reduce the amyloid burden in the brain, but they do so at different stages of plaque formation. This difference in mechanism may partly explain why their clinical trial results and side effect profiles are not identical.

What Does the Research Show About Effectiveness?

In the major clinical trials—Clarity AD for lecanemab and TRAILBLAZER-ALZ 2 for donanemab—both drugs showed a statistically significant slowing of cognitive decline. Lecanemab slowed decline by 27% over 18 months, while donanemab showed a 35% slowing over the same period. However, experts caution against directly comparing these numbers because the trials had different designs, patient populations, and ways of measuring outcomes. Preliminary real-world data presented at the Alzheimer's Association International Conference in 2025 suggests that both drugs perform comparably to the trial results, with similar or even better safety profiles in everyday clinic settings. Many patients and families report being satisfied with the results, though individual responses vary.

What About Side Effects and Safety?

Both drugs carry a risk of a side effect called ARIA (amyloid-related imaging abnormalities), which can involve brain swelling or small bleeds. In the trials, about 21% of lecanemab users experienced some side effect, with ARIA being the most concerning. Donanemab had a slightly higher rate of ARIA, particularly brain swelling. Most ARIA is mild and resolves on its own, but it requires regular MRI monitoring. Other common side effects include infusion-related reactions (like fever or chills) and headache. Because these are intensive treatments, patients need to be in good overall health and have a care partner who can help manage the schedule and watch for symptoms like confusion, headache, or vision changes.

General caregiving information, not medical advice. Check medications and major care changes with your clinician.

Step-by-step

  1. Confirm early Alzheimer's with amyloid biomarker evidence (PET scan or spinal fluid test) and review health history — including bleeding disorders, blood-thinner use, and baseline MRI — with the clinician to gauge ARIA risk and confirm eligibility.

  2. Understand the treatment schedule: lecanemab is an IV infusion every two weeks, donanemab every four weeks; both require a long-term commitment to regular visits at an infusion center.

  3. Plan for a care partner to attend appointments and watch for ARIA symptoms (new or worsening headache, confusion, vision changes, dizziness, nausea, or falls).

  4. Ask the doctor which current medications can continue; older drugs like donepezil and memantine are generally safe to take alongside anti-amyloid treatments.

  5. Sort out finances early: Medicare Part B covers both drugs for eligible patients, but prior authorization is common; call your insurer to clarify copays, infusion coverage, and out-of-pocket costs.

  6. Hold realistic expectations: these drugs modestly slow decline over months, not reverse damage; the doctor will reassess cognition at 3 and 6 months to decide whether to continue.

What not to do

  • Don't assume one drug is 'better' based solely on trial percentages; the trials were not directly compared, and individual response varies — ask the doctor which is more appropriate for your loved one's amyloid burden, health status, and tolerance for infusion frequency.

  • Don't stop current memory medications (donepezil, memantine) without talking to the doctor; they address symptoms and can be safely taken alongside lecanemab or donanemab.

  • Don't dismiss potential side effects like headache, confusion, or vision changes as normal aging or dementia; these could be ARIA and need prompt evaluation.

  • Don't try to get both drugs or adjust the dose upward; patients take one at a fixed dose, reduced only if side effects occur.

  • Don't assume qualification just because of early Alzheimer's; strict criteria include confirmed amyloid biomarker and no contraindications like uncontrolled bleeding disorders or certain brain conditions.

Practical tools

  • Questions for the Doctor: Lecanemab vs Donanemab

    Printable checklist: (1) Is amyloid confirmed? (2) Which drug is safer given health history? (3) Infusion frequency? (4) MRI monitoring schedule? (5) Can current memory medications continue? (6) Expected out-of-pocket costs?

  • Side Effect Diary & Communication Script

    Daily log for headache, confusion, vision changes, dizziness, nausea — note date, time, severity. If a symptom appears, say: 'I noticed [name] has had a headache since yesterday and seems more confused. Should we call the neurologist or go to urgent care?'

  • Infusion Day Checklist

    Before: confirm appointment, bring insurance card and ID, pack snack and water, bring a book or tablet, arrange a driver. After: monitor for 24 hours for any reaction.

  • Medication Comparison Table

    Lecanemab: IV every 2 weeks, targets protofibrils, 27% slowing (Clarity AD), by Eisai. Donanemab: IV every 4 weeks, targets mature plaques, 35% slowing (TRAILBLAZER-ALZ 2), by Eli Lilly. Both require regular MRI and carry ARIA risk.

  • Support Group Resource

    Alzheimer's Association 24/7 helpline (800-272-3900) and local chapters connect families with those experienced in lecanemab or donanemab — a source of practical wisdom and encouragement.

Discuss with your clinician

Ask your doctor: 'Based on my loved one's amyloid PET scan or spinal fluid results, are they a candidate for lecanemab or donanemab?'

Ask: 'What is the plan for MRI monitoring before and during treatment to check for ARIA?'

Ask: 'If my loved one is on a blood thinner, is it safe to start either drug, and do we need to stop the blood thinner temporarily?'

Ask: 'What are the out-of-pocket costs we should expect, and does our insurance cover the infusions and required MRIs?'

Ask: 'How will we decide whether to continue or stop the drug after 6 months if there is no improvement?'

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