By Sumathi Reddy

After the FDA approved a controversial new Alzheimer’s drug, doctors have been fielding lots of questions about it from patients and their caregivers.

The drug, called Aduhelm and made by Biogen, removes amyloid, a sticky substance in the brain that is a defining feature of Alzheimer’s disease. But some doctors say it’s unclear whether removing amyloid will actually slow the progression of the disease. Clinical trials yielded mixed results.

On Thursday, Biogen said the FDA had narrowed the prescribing instructions for the drug, recommending the therapy be given to people with early-stage symptoms of the disease. Initially, the FDA approved Aduhelm in June for all Alzheimer’s patients.

Alzheimer’s, a progressive brain disorder that affects memory and cognitive skills, is the most common cause of dementia. Its biological hallmark is sticky protein clusters—called amyloid plaques—in the brain, as well as tangles of fibers, composed of tau protein.

We asked doctors what patients need to know about the new drug—and what questions they should be asking their doctors.

What is this new treatment and what does it involve?

Aduhelm is a monthly infusion that can be done at an infusion center or a doctor’s office. It’s unclear how long patients would need to take it; the clinical trials ended after a year.

Patients undergoing treatment must also get periodic MRI scans to see if they develop small brain bleeds or brain swelling, which are the most common side effects of the treatment.

What does the drug do and why is it controversial?

In clinical trials, the treatment was effective at removing amyloid from the brain. But it’s unclear exactly what effect that will have for patients. One trial showed some patients had a slower cognitive decline than those taking a placebo, but another trial didn’t show that. So some experts think more conclusive evidence is needed to justify the risks and cost associated with the treatment.

Patients who showed positive results experienced a modestly slower progression of disease, but not a reversal of symptoms or improvements in memory or cognition. “The expectation is that there will be a modest slowing of decline,” says Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute at the University of Southern California, who is also a consultant to Biogen and worked on the development of the drug.

The treatment would work over years, not weeks or months. Dr. Aisen estimates that patients with mild cognitive impairment, which is often a precursor to dementia, might get an extra year or two before they start losing their ability to function independently.

What are the main side effects?

In clinical trials, more than a third of patients who took Aduhelm had small brain bleeds or an accumulation of fluid detected by MRI. Most of the time, the problem resolved on its own, but some people reported confusion or dizziness. And there is a small risk that a more serious complication could develop, such as a macro hemorrhage or major edema. Patients whose MRI scans show brain bleeds should pause treatment.

How much does the treatment cost and will insurance cover it?

Biogen set the price of the drug at about $56,000 a year, which alarmed many doctors and patients. Doctors and patients are waiting to see if the Centers for Medicare and Medicaid Services, the federal agency that oversees the health insurance program for seniors, will provide coverage for the treatment. Private insurers often follow the lead of CMS. A CMS spokesperson said the agency is reviewing the FDA’s decision and will have more information soon.

Who is eligible for Aduhelm?

The FDA is now recommending it only for patients in early stages of the disease. Doctors agree that the only patients who should receive the treatment are those with milder memory symptoms or in the early stages of disease, because that is who it has been tested on.

What was the profile of the patients in the clinical trials?

In the clinical trials, the majority of patients had mild cognitive impairment, often referred to as MCI, and some had mild dementia due to Alzheimer’s. MCI is an early stage of memory loss and cognitive decline in which people can still independently perform daily activities. Many people diagnosed with MCI go on to develop dementia. In mild dementia, some help is needed with daily activities but individuals can still manage their personal care, such as bathing and dressing, without assistance.

All the trial participants had amyloid in their brains.

What about patients with moderate or severe Alzheimer’s. Can they get the treatment? Should they?

Doctors can still prescribe Aduhelm to patients who fall outside the parameters set by the FDA. After a drug is approved by regulators, doctors are free to prescribe it for any reason they deem fit, known as “off-label” prescribing. But insurers often restrict paying for expensive medicines based on the FDA’s criteria.

What’s more, many doctors say they wouldn’t recommend Aduhelm for these patients because there isn’t yet safety and efficacy data for people with more severe disease.

“Patients with moderate or severe dementia are unlikely to benefit from this drug,” says Dylan Wint, director of the Lou Ruvo Center for Brain Health at Cleveland Clinic in Las Vegas, who has no financial relationship with Aduhelm and wasn’t involved in the drug trials. “If someone is already having difficulty with basic activities of daily living—dressing, grooming, or feeding themselves—this drug is unlikely to help them and I would not recommend it for them.”

I have MCI or mild Alzheimer’s disease. Am I a good candidate for this treatment?

Possibly. But doctors say there are several important steps that need to be taken first.

You should get an MRI to see if you have any existing microbleeds before starting treatment. If a patient has four or fewer microbleeds, they can proceed with considering the treatment, says Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center and a consultant for Biogen. But if they have five to nine bleeds, there needs to be more careful consideration, and such patients might be excluded from treatments. Mayo is still developing its guidelines, but Dr. Petersen anticipates that if a patient has 10 or more microbleeds, the center will advise against treatment.

Any other tests I need to get done?

Yes. Patients also need to make sure they have amyloid in their brain, says Dr. Aisen. Roughly 25% to 30% of people diagnosed with Alzheimer’s disease based on clinical symptoms are misdiagnosed because they don’t, in fact, have amyloid deposits in their brain, he says. Amyloid is generally tested for via a PET scan or spinal tap.

I have a MCI diagnosis, proof of amyloid in my brain, and no microbleeds. Anything else I should do?

Some experts say it’s a good idea to do genetic testing to see if a patient carries the APOE4 gene, which is associated with a heightened Alzheimer’s risk. About 20% of the population has one or two copies of the e4 variant of the apolipoprotein E or APOE gene. Such tests can be done through a blood test or direct-to-consumer tests.

APOE4 carriers have an increased risk of microbleed side effects from the treatment, says Dr. Petersen. So a patient may decide against the treatment if they have the e4 variant or they may have to be monitored more regularly with MRI scans.