15 Things to Know About the Disease-Slowing Alzheimer’s Drugs

More concerning, however, is when amyloid-related imaging abnormalities (ARIA) occur, which can include brain swelling or bleeding or both. “ARIA can be mild, moderate or severe,” Budson says. “When severe, it can be serious and life-threatening.”

While patients taking Kisunla experienced more ARIA than those on Leqembi, the researchers point out that the two drugs were not compared against each other in the studies. 

“I have many patients on each medication, and I feel confident that I am doing a service to my patients with each medication and not exposing one group to greater risks than the other,” Schulz says.

Internist Dr. Mia Yang, associate professor of gerontology and geriatrics at Wake Forest School of Medicine who also practices at Atrium Health Neurology, prints out an article from the Annals of Internal Medicine for her patients when discussing the new drugs. She points out that the drugs are risky for patients with medical conditions that make it likely they will experience a heart attack, an ischemic stroke or a blood clot in the legs or lungs in the next one to two years. “The deaths that occurred during the trials were most commonly in patients who received additional blood thinner,” she says.

“ARIA remains the main [side effect], and they definitely happen both anecdotally in our experience as well as in hearing from others,” she wrote in an email. Budson pointed to a recently released study that examined a modified dosing schedule of Kisunla that reduced the overall risk of brain swelling to 16 percent, “which is similar to the 12.6 percent [of Leqembi],” he wrote in an email.

5. Do the benefits outweigh the risks?

For Yang, the benefits outweigh the risks “only in those who have Alzheimer’s as their main problem” and who are willing to take on the risk of intracranial bleed “and the burden of multiple MRIs, biweekly or monthly infusions, and who live within a reasonable driving distance to their infusion site and health system to get repeat MRIs,” she wrote in an email. The MRIs, she says, are needed to “accurately and timely capture ARIAs and associated symptoms,” such as headaches and dizziness.

Moreover, the “benefit is modest in cognition; both groups worsen over time,” she says. “The drug is very good at removing amyloid, but amyloid does not equal Alzheimer’s dementia or dementia in general.”

Dr. David Jones, a Mayo Clinic neurologist who prescribes Leqembi for some of his patients, urges prudence. “I approach their use with a cautious attitude toward the risk/benefit equation,” he wrote in an email. “These drugs are certainly not the right choice for everyone, but they can be appropriate for some patients.”

6. Who are the best candidates for these drugs?

The drugs typically are recommended for those age 60 or older with Alzheimer’s disease as the primary cause of cognitive impairment. The diagnosis must be confirmed by lumbar puncture or amyloid PET scan and blood tests to ensure nothing else is responsible for the symptoms, such as medication, for example, or a prior stroke.

Patients also should undergo cognitive testing, either the MoCA (short for Montreal Cognitive Assessment) or the Mini-Mental State Examination, Budson says.

Yang typically prescribes the drugs to patients in their early 60s who most likely have early-onset Alzheimer’s disease and are otherwise healthy, but only after an extensive discussion of the risks and benefits.

If you think you are developing dementia — especially if your symptoms are mild — waste no time in getting evaluated, Schulz says, adding that starting one of these drugs as early as possible is very important. “As soon as you have an inkling of symptoms, get seen,” he says. “If it’s nothing, that’s OK. But the earliest you can catch it, the better.”

The drugs are most effective when the patient still can function normally or has only minor difficulty with complicated tasks, such as paying bills and taking medications, Budson says.

7. Should certain people avoid these drugs?

Very important: Potential patients should undergo genetic testing for the APOE e4 gene mutation. APOE e4 raises the risk of Alzheimer’s but also increases the possibility of ARIA. Patients with two copies of the gene, meaning one from each parent, should not take the drugs, Budson says. Those with only one copy must be carefully monitored if they take the drugs. “Patients with two copies of this gene have more side effects, and the medication does not seem to work as well,” says Dr. Alison O’Donnell, medical director for VA Pittsburgh Healthcare System’s Center for Cognitive Health.

Patients should not take the drugs if they have bleeding problems or if they are on certain blood thinners. Also, they must be able to tolerate having MRIs, which are necessary to monitor for side effects.

8. Are there differences between the drugs that might make one more suitable for a person than the other?

Both remove amyloid from the brain, but they work at different stages of amyloid plaque formation. Leqembi is an IV infusion given every two weeks, while Kisunla is an IV infusion given every four weeks. “Less frequent infusions might make donanemab [Kisunla] more appealing to some patients,” O’Donnell says.

9. Once I am taking one of these drugs, what kind of monitoring is required?

You must undergo regular MRIs to ensure there are no side effects, especially microscopic brain bleeds or brain swelling associated with ARIA.

10. Will my insurance cover the testing? The drugs?

The drugs are quite expensive. Medicare covers 80 percent if specific criteria are met and the prescribing doctor participates in a registry to gauge the drug’s effectiveness. Patients should check with their supplemental plans to see what additional costs may be covered. Other insurance coverage, including Medicare Advantage plans, may vary, depending on the plan, Schulz says.

11.  What should I expect in the way of results if I take one of these drugs?

The research, which was conducted over 18 months, suggests “you get an additional six months of better quality of life for every 18 months, if you start early and keep using them,” Budson says. But Schulz cautions that it is still unclear how long these benefits will last. “We are still following those patients to give more guidance,” Schulz says. “As of this time, we don’t know whether we can say that we delay things six months for every 18 months. What we can say is that it is true for the first 18 months.”

One recent “real world” study — that is, an observational study conducted outside of tightly controlled clinical trials — in Israel found Leqembi was “generally safe,” although many patients still experienced some decline in memory and thinking over time, especially younger ones. Side effects were mostly mild, but brain swelling or small brain bleeds (ARIA) happened in some cases and needs careful monitoring.

12. Are there other options, and what are their side effects?

There are no other FDA-approved treatments shown to slow cognitive decline in Alzheimer’s disease, though there are other drugs that deal with certain symptoms. These other treatments would be taken along with Leqembi or Kisunla, “so it isn’t an either/or situation,” Budson says.

13. Does efficacy wane over time? Do you have to take higher doses (like with Parkinson’s drugs) to get the same effects?

Unlikely. Data presented at the 2024 Alzheimer’s Association International Conference showed that patients on Leqembi continue to benefit compared with matched controls through at least 36 months of treatment, O’Donnell says.

14. Must the drugs be taken for life?

Opinions vary. At this time, Leqembi appears to need continuous treatment to maintain its benefits, O’Donnell says. Kisunla may be able to be stopped if amyloid levels decrease.

“The science isn’t 100 percent clear here, but for both drugs, I believe a lot of us will see how individual patients do and make a decision as to whether to continue or stop the medications,” Schulz says, adding that so far, for Kisunla, “the data show no sudden decline as a result of stopping.”

15. Which physicians are qualified to prescribe these therapies?

“If I was a patient, I would ask the physician: ‘Do you think of yourself as an Alzheimer’s specialist?’ ” Karlawish says. Usually, these are neurologists, geriatricians or psychiatrists who can make a diagnosis and who know how to prescribe and monitor these drugs. “Often they work at memory centers or an Alzheimer’s disease center,” he adds.