Q&A: A Neurologist's Take on the New Chapter for Alzheimer's Care

Dr. Chun Lim Discusses How BIDMC Will Be the First MA Hospital To Provide Lecanemab To Patients and the Importance of the Medical Milestone

An estimated 6.7 million adults in the U.S. are diagnosed with Alzheimer’s disease, an irreversible, progressive brain disorder that slowly destroys memory, cognitive skills, and eventually the ability to carry out simple tasks. Alzheimer’s disease, which affects about five percent of adults 65 and older and 30 percent of adults 85 and older, is a significant and growing public health concern across the country as the aging population contributes to the rise in Alzheimer’s cases.

In July 2023, the U.S. Food & Drug Administration (FDA) gave traditional approval to lecanemab-irmb, the first medication shown in brain scans to reduce amyloid beta plaque in the brain, a marker of Alzheimer’s disease. Starting in September, Beth Israel Deaconess Medical Center (BIDMC) will be the first site in Massachusetts to offer the treatment to patients. The milestone was made possible by a multidisciplinary collaboration spearheaded by Daniel Press, MD, chief of Cognitive Neurology, Chun Lim, MD, PhD, medical director of Cognitive Neurology, Lynn Shaughnessy, PsyD, director of Neuropsychology, and Stephanie Buss, MD, research director of Cognitive Neurology. We asked Dr. Lim what providing the long hoped-for medication will mean to patients, their families and to care teams.

What's the best-case scenario for a patient who gets this medication?

In a population analysis from a clinical trial, participants who received lecanemab showed about a 30 percent slowing of decline along with reduction of beta-amyloid in the brain compared to a control group who received a placebo. We hope our patients have similar responses. By the end of the trial, there were a number of patients who actually had no detectable levels of beta-amyloid. The best-case scenario is that this medicine is a disease modifying therapy that can slow down the progression of Alzheimer’s disease.

Apart from the reduction of amyloid plaques in the brain – which is seen in brain scans – what improvements might physicians, patients and caregivers be able to see in patients who receive this medication?

In the phase III study that led to FDA approval, researchers looked at a variety of different physiological and behavioral markers. They looked at caregiver reports on patients’ day-to-day activities—how would you characterize the severity of their memory issues, how much socializing are they doing, how much of the daily chores and hobbies are they able to do? They also used cognitive testing to evaluate different brain processes including memory, language, thinking and judgement.

Lecanemab slows the decline by about 30 percent over 18 months of treatment. This would be equivalent to a 5-month difference, in other words, patients on lecanemab only declined the equivalent of 13 months during their 18 months of treatment.

Who makes a good candidate for this medication?

First, patients require a formal diagnosis of Alzheimer’s disease with either a PET scan of the brain for amyloid plaque or through a lumbar puncture. Once a patient has a formal diagnosis, a good candidate for this medication would be someone that is in the earlier stages of Alzheimer’s disease.

This is a medication that you take via transfusion every 2 weeks, requires frequent MRI and doctor visits, so it’s a pretty involved process. It’s important that patients who go through this course of treatment have a caregiver who can help them through it.

Who wouldn’t make a good candidate for this medication or would not be eligible?

Unfortunately, this medicine isn't for all Alzheimer’s patients as it has only been shown to be helpful for those with mild disease. As the disease progresses to a more moderate stage, lecanemab is no longer able to slow down the progression of the disease.

Beyond that, there is a genetic test that we do. The apolipoprotein E (APOE) gene is a major genetic risk factor for Alzheimer's disease. You can have three different alleles–or variants–of this gene. The one that is the most highly associated with Alzheimer's disease also confers a risk for serious complications and side effects from the medication. Because of that heightened risk, we are not able to offer lecanemab to people with two copies of this gene variant.

Can you speak to the infusion process briefly?

Patients take lecanemab via IV infusion for about an hour every two weeks. Over the course of a year, patients take 26 infusions. We don't know exactly how long patients will be undergoing treatment, but we are assuming 18 months, or about 40 infusions per patient.

In the beginning of treatment, we monitor patients for several hours after infusion to mitigate any potential reactions. Eighty percent of patients in the clinical trial tolerated their infusions without any problem. Limited to the first few infusions, 20 percent had mild- to moderate- transfusion reactions, such as headaches, nausea, dizziness, hypotension, adequately treated just with Tylenol or Benadryl. A small percentage — about 1 percent or less—may have a more serious reaction which would require something stronger like steroids or possibly hospitalization, which we watch closely for as they are acclimating to the medication.

It sounds like it may be hard to meet the demand for this long-awaited medication.

That’s true, but we are doing our best to distribute this highly in-demand medication as equitably as possible. We set up a clinic designated specifically for evaluating patients for this treatment. We also have a unique registry that we started about six or nine months before this medication was approved so that we can evaluate and prioritize patients in a more equitable manner. All patients who are scheduled for infusion need to first be enrolled in a registry approved by the Centers for Medicare & Medicaid Services (CMS). While most institutions are using the CMS national registry, BIDMC is the only institution in the U.S. that has an individual CMS-approved study and registry.

What has this new medication meant to you as a long-time neurologist?

For many, many years, neurologists have had to rely on non-disease modifying therapies of minimal benefit. Most of what we were doing was to ensure our patients were in a safe and enriching social environment.

But, this is the beginning of a new chapter. Even though this medication may only reduce symptoms by 30 percent, it adds to our multipronged approach to patient care in a powerful way to have an even more positive effect on these patients’ lives. So, yes, we are very excited about this.

This conversation has been edited for length and clarity.