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Donanemab (brand name Kisunla) is a new medicine approved to treat people with early-stage Alzheimer’s disease, specifically those with mild cognitive impairment or mild dementia. It works by helping the body clear amyloid plaques from the brain, which are thought to play a role in Alzheimer’s disease.[1][2]

In this blog we will discuss clinical trial TRAILBLAZER-ALZ 2 which studied Donanemab infusions and its benefits and risks in early Alzheimers patients.

In this large clinical trial (TRAILBLAZER-ALZ 2) over 1,700 people with early Alzheimer’s disease received either donanemab or a placebo (inactive treatment) for about 18 months. Donanemab was given as an intravenous (IV) infusion every 4 weeks. The study measured changes in thinking, memory, and daily function over time.[2]

Benefits

People who received donanemab had a slower decline in memory, thinking, and daily activities compared to those who received placebo. On average, donanemab slowed the progression of symptoms by around 35% over 18 months. This means that, while Alzheimer’s disease still progressed, it did so more slowly for those on donanemab.[2][4][5]

Risks and side effects

The most important risk with donanemab is a side effect called amyloid-related imaging abnormalities (ARIA). ARIA can show up as swelling or small areas of bleeding in the brain, usually seen on MRI scans. Most cases are mild and don’t cause symptoms, but some can be serious. About 1 in 4 people treated with donanemab had ARIA which in most patients did not recur on subsequent infusions. The second type of side effect included symptoms experienced by the patient. The most frequent of these were headaches, confusion, dizziness, and very rarely, stroke-like symptoms. Although patients did not actually have strokes, the symptoms appeared similar from the outside. Further investigation with brain MRI clarified that these symptoms were due to the medication, not a stroke. In rare cases, serious complications or death occurred.Rarely, serious complications or death occurred. Other possible side effects include infusion reactions (such as chills or fever) and allergic reactions. [2][4][6]

Imaging and follow-up

Because of the risk of ARIA, regular MRI scans were done before and during treatment. MRIs were done before starting donanemab, and then before the 2nd, 3rd, 4th, and 7th infusions. If at any point in time patients developed side effects or if they were felt to be at higher risk for side effects additional MRIs were preformed. If ARIA was found, treatment was paused or stopped. [3][6]

Who benefits most?

Donanemab is most helpful for people in the early stages of Alzheimer’s disease—those who have mild memory loss or mild problems with thinking and daily activities. Before starting treatment, doctors confirm the presence of amyloid plaques in the brain using a special scan called a PET scan.[2][3]

Who should not take donanemab?

Donanemab is not recommended for people with more advanced Alzheimer’s disease, or those with certain findings on MRI (such as many small brain bleeds or other major brain problems). Your doctor will review your medical history and test results to decide if donanemab is right for you.[3]

What to expect

Donanemab is given as a monthly IV infusion. You will need regular check-ups and MRI scans to monitor for side effects. The decision to start donanemab should be made together with your doctor, considering your health, goals, and preferences.

Infusion and MRI schedule in TRAILBLAZER-ALZ 2 clinical trial

For the last two years, Dr. Sadikovic has been treating patients with Alzheimer's dementia using Donanemab and similar classes of medications. She has significant experience with this novel treatment. Dr. Sadikovic can help you understand the risks and benefits, and guide you through the process.

If you have questions about Alzheimer’s disease treatment, please call us. At Direct Neurology, we look forward to guiding you in your neurological care.

References

1. FDA Orange Book. FDA Orange Book.

2. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. Sims JR, Zimmer JA, Evans CD, et al. JAMA. 2023;330(6):512-527. doi:10.1001/jama.2023.13239.

3. Donanemab: Appropriate Use Recommendations. Rabinovici GD, Selkoe DJ, Schindler SE, et al. The Journal of Prevention of Alzheimer's Disease. 2025;12(5):100150. doi:10.1016/j.tjpad.2025.100150.

4. Antiamyloid Monoclonal Antibody Therapy for Alzheimer Disease: Emerging Issues in Neurology. Ramanan VK, Armstrong MJ, Choudhury P, et al. Neurology. 2023;101(19):842-852. doi:10.1212/WNL.0000000000207757.

5. Posttreatment Amyloid Levels and Clinical Outcomes Following Donanemab for Early Symptomatic Alzheimer Disease. Lu M, Kim MJ, Collins EC, et al. JAMA Neurology. 2025;:2839837. doi:10.1001/jamaneurol.2025.3869.

6. Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials. Zimmer JA, Ardayfio P, Wang H, et al. JAMA Neurology. 2025;82(5):461-469. doi:10.1001/jamaneurol.2025.0065.