Exploring Donanemab: A New Hope for Early-Stage Alzheimer’s Disease

Understanding Donanemab and Its Role in Alzheimer’s Treatment

Donanemab (brand name Kisunla) is a groundbreaking medication approved for treating individuals with early-stage Alzheimer’s disease. This includes those experiencing mild cognitive impairment or mild dementia. The drug works by assisting the body in clearing amyloid plaques from the brain, which are believed to contribute to the progression of Alzheimer’s disease.[1][2]

In this blog, I want to share insights from the clinical trial TRAILBLAZER-ALZ 2, which investigated the effects of Donanemab infusions, along with its potential benefits and risks for early Alzheimer’s patients.

The TRAILBLAZER-ALZ 2 Clinical Trial

In this extensive clinical trial, over 1,700 participants with early Alzheimer’s disease received either Donanemab or a placebo (an inactive treatment) for approximately 18 months. Donanemab was administered as an intravenous (IV) infusion every four weeks. The study aimed to measure changes in thinking, memory, and daily functioning over time.[2]

Benefits of Donanemab

Participants who received Donanemab experienced a slower decline in memory, cognitive function, and daily activities compared to those who received the placebo. On average, Donanemab slowed the progression of symptoms by about 35% over the 18-month period. While Alzheimer’s disease still progressed, it did so at a reduced rate for those on Donanemab.[2][4][5]

Risks and Side Effects

The primary risk associated with Donanemab is a side effect known as amyloid-related imaging abnormalities (ARIA). ARIA can manifest as swelling or small areas of bleeding in the brain, typically identified through MRI scans. Most cases are mild and asymptomatic, but some can be serious. Approximately 1 in 4 individuals treated with Donanemab experienced ARIA, although most patients did not see a recurrence with subsequent infusions.

Other side effects included headaches, confusion, dizziness, and, in rare instances, stroke-like symptoms. While these symptoms may appear similar to those of a stroke, further investigation with brain MRI confirmed they were medication-related. In rare cases, serious complications or even death occurred. Other potential side effects included infusion reactions (such as chills or fever) and allergic reactions.[2][4][6]

Imaging and Follow-Up Procedures

Due to the risk of ARIA, regular MRI scans were conducted before and during treatment. MRIs were performed before starting Donanemab and then before the 2nd, 3rd, 4th, and 7th infusions. If patients developed side effects or were deemed at higher risk for complications, additional MRIs were conducted. If ARIA was detected, treatment was paused or discontinued.[3][6]

Who Benefits Most from Donanemab?

Donanemab is particularly beneficial for individuals in the early stages of Alzheimer’s disease—those experiencing mild memory loss or minor issues with thinking and daily activities. Before initiating treatment, doctors confirm the presence of amyloid plaques in the brain using a specialized scan called a PET scan.[2][3]

Who Should Avoid Donanemab?

Donanemab is not recommended for individuals with more advanced Alzheimer’s disease or those with specific findings on MRI, such as numerous small brain bleeds or other significant brain issues. Your doctor will carefully review your medical history and test results to determine if Donanemab is appropriate for you.[3]

What to Expect When Starting Donanemab

Donanemab is administered as a monthly IV infusion. Regular check-ups and MRI scans will be necessary to monitor for side effects. The decision to begin treatment with Donanemab should be made collaboratively with your doctor, taking into account your health, goals, and preferences.

Infusion and MRI Schedule in the TRAILBLAZER-ALZ 2 Clinical Trial

My Experience with Donanemab

For the past two years, I have been treating patients with Alzheimer’s dementia using Donanemab and similar classes of medications. My experience with this novel treatment has been significant. I can help you navigate the complexities of understanding the risks and benefits associated with Donanemab and guide you through the treatment process.

If you have questions about Alzheimer’s disease treatment, please reach out to us. At Direct Neurology, we are committed to providing compassionate and comprehensive neurological care tailored to your needs.

The Value of Investing in Better Health

Investing in your health is one of the most important decisions you can make. It’s not just about managing symptoms; it’s about enhancing your quality of life. By exploring innovative treatments like Donanemab, you take a proactive step towards a healthier future.

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.