Over the past year-and-a-half, more than 100 people have received new disease-modifying drugs for Alzheimer’s disease at the Indiana University Health Neuroscience Center in downtown Indianapolis, and that number grows weekly. Not only are the patients among the first people in the country to receive the treatment, but they’re contributing to the work of researchers from the IU School of Medicine who are actively studying the long-term effects of the drugs.
The Food and Drug Administration-approved drugs, lecanemab and donanemab, remove the buildup of amyloid protein plaques in the brain — a hallmark characteristic of Alzheimer’s disease. While the drugs do not stop the disease or lead to cognitive improvement, they can “freeze” a person in their current functional state, potentially providing several additional years of independence if the disease is caught early, said Jared Brosch, MD, associate professor of clinical neurology at the IU School of Medicine.
“It’s exciting that we’ve given that opportunity to our patients to be on the cutting edge,” he said.The Center for Neurodegenerative Disorders in the IU School of Medicine-IU Health Neuroscience Institute oversees the administration of the drugs through its brain health program, which began in 2023, that connects patients and their families with a brain health navigator to work with them throughout their treatment journey.
A new pathway for patients
Donna Wilcock, PhD, the Barbara and Larry Sharpf Professor of Alzheimer’s Disease Research at the IU School of Medicine and the director of the Center for Neurodegenerative Disorders, said the program has screened more than 300 people since 2023. Nearly one third of those screened have received the treatment, which is administered through intravenous infusions every two weeks. After the seventh infusion, Wilcock said, the patients can visit one of the IU Health suburban Indianapolis infusion centers if it’s more convenient than traveling to downtown Indianapolis.
The program collaborates with a comprehensive team of faculty experts in the IU School of Medicine’s Department of Neurology, Department of Medicine’s Division of General Internal Medicine and Geriatrics and Department of Family Medicine to refer and pre-screen patients for the program.
Wilcock said the program’s brain health navigators help guide patients and their families from the initial screening process throughout treatment. The navigator first reviews a patient’s medical record and gives an overview of the treatment expectations. Patients will then receive:
- A cognitive battery test to assess memory, attention and language.
- An MRI to check for pre-existing vascular injuries, like mini-strokes or microbleeds.
- A lumbar puncture (spinal tap) or an amyloid PET scan to confirm amyloid in the brain.
- Genotyping for a common risk variant for Alzheimer’s disease (APOE4).
- Consultation with a behavioral neurologist to review the screening results.
“Through the screening reviews and clinical trial data, we're setting appropriate expectations for treatment and any adverse effects of the drugs,” Wilcock said. “Then it's shared decision making between our team and the patient as to whether they want to pursue the therapy.”
In 2024, the program hired a social worker who has developed patient support groups and care partner support groups.
“Patients receiving these novel therapies have many questions, as do their loved ones,” Wilcock said. “By adding a social worker and support groups, they can share experiences, ask questions about their disease and the treatment and get access to resources as their care needs change. This has been an important addition to enhance the care of our patients and their families.”
Wilcock said as the brain health program continues to grow, so have advancements in the treatments. In the next year or so, lecanemab is anticipated to be offered as a subcutaneous injection as well as the traditional infusion. This will open availability of the drug more broadly, she said, especially to rural Hoosiers who cannot travel to Indianapolis.
“This would be something they could probably pick up in the pharmacy," Wilcock said. "So, we're going to have to ramp up our screening process for eligibility and the capacity of the brain health program to be able to operate on a broader scale and do it virtually and at remote sites.”
The success of the brain health program’s administration of the drugs could lend itself to other treatments for neurodegenerative disorders, Wilcock said. In coordination with movement disorders specialists in the Department of Neurology, the team is exploring adapting the model to administer an updated Parkinson’s disease treatment.
Building upon years of research
In 2023, lecanemab, marketed as Leqembi, was the first amyloid beta-directed monoclonal antibody to receive traditional approval from the FDA. Next came donanemab, marketed as Kisunla by Indianapolis-based Eli Lilly and Co., which received FDA approval in 2024.
The development of these two drugs marked a shift in how clinicians approach their care for Alzheimer’s disease patients.
For more than 25 years, scientists and pharmaceutical companies have been attempting to develop a treatment for the disease, and countless drugs have failed in clinical trials. Many of those treatments targeted people in later and more severe stages of the disease; lecanemab and donanemab, however, are for people in early stages of Alzheimer's disease.
Researchers at the IU School of Medicine have been testing both drugs in clinical trials since the late 2010s. Brosch, who led clinical trials for each of the drugs, said over 70% of trial participants who received lecanemab were able to live independently and continued to do so after a year and a half of treatment.
“It slows the progression to a point where it’s hard to notice that person is progressing while they’re on the drug,” Brosch said.
Although clinical trials for both drugs have ended, IU School of Medicine researchers have continued investigating the treatments and the long-term impact on patients.
Wilcock leads a study on the adverse effects of the drugs — called amyloid-related imaging abnormalities (ARIA) — including brain bleeding and swelling. Physicians identify these changes on MRI scans. In clinical trials, between 20% and 30% of participants had ARIA, but only about 3% to 6% had symptoms, which may include headache, nausea and dizziness.
While Wilcock’s research investigates the adverse effects in animal models, the brain health program team has seen a low the rate of ARIA in human patients — about 8% — through their dedication to patient education about cardiovascular risk factors and blood pressure.
Near the end of 2023, Eli Lilly and Co. gave a presentation at a conference about a machine learning model that identified high blood pressure as the second-highest risk factor for ARIA in patients who have taken a disease-modifying drug to treat Alzheimer’s disease.
Following the presentation, Wilcock said the team created a plan to counsel patients about monitoring their blood pressure at home if they take an antihypertensive medication. Patients also get their blood pressure taken before they start an infusion. If it’s elevated and remains high after a period of rest, then they do not receive an infusion that day, Wilcock said.
“We're doing a really good job of preventing ARIA by making sure patients are well educated and are proactive with the cardiovascular risk factors,” she added.
The brain health program also has a dedicated research coordinator at the IU School of Medicine that closely works with the clinical team. They collect and bank patient plasma samples from patients, working with the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), and are analyzing clinical MRI scans of patients.
Wilcock said the team is exploring a grant to investigate predictive biomarkers of ARIA in blood and MRIs. Studying biometric signatures will allow IU School of Medicine researchers to better identify people who are at risk of adverse events and those who stand to benefit the most.
The program has also partnered with the Alzheimer’s Association to contribute to its Alzheimer’s Network for Treatment and Diagnostics, or ALZ-NET. IU School of Medicine was one of the first academic sites to participate in the initiative after it was announced in 2022, Wilcock said.
ALZ-NET collects clinical and safety data from patients receiving the FDA-approved disease-modifying treatments across the United States, tracking long-term health outcomes associated with their use in real-world settings as well as demographic data to better understand health disparities. Wilcock said the national network of data will next expand so MRI images from patients can be accessed and analyzed by researchers throughout the country.
"And with that comes power," Wilcock said. "The more samples and the more cases you have, the better the analysis is going to be."
