CNN — Imagine you have just been diagnosed with mild cognitive decline due to Alzheimer’s disease. Your doctor might suggest taking one of the newer medications such as lecanemab or donanemab, which have been shown in clinical trials to clear plaque-causing amyloid proteins from the brain that are the hallmark of Alzheimer’s.
Both drugs require time-consuming biweekly or monthly infusions, however, and carry the risk of life-threatening swelling or bleeding in the brain. Then there’s the expense — even on Medicare, co-pays for the year can be thousands of dollars.
Are these downsides worth the risk? You may decide the answer is yes if you knew how much longer you might live independently, said Dr. Sarah Hartz, a professor of psychiatry at the Washington University School of Medicine in St. Louis. She is the lead author of a new study that estimated the amount of time people might continue to perform daily activities without assistance after beginning lecanemab, marketed as Leqembi, or donanemab, marketed as Kisunla.
“Patients want to know how long a drug will allow them to keep driving, pay their own bills, cook at home and dress themselves,” Hartz said.
Calculations ranged from eight months to an additional 39 months of independent living, depending on the severity of the disease when medication was started.
“We wouldn’t want people to count on these numbers as definitive, however, because it’s just an estimate and depends on the person and where they are at in their cognitive decline,” Hartz said. “Instead, they should use these estimates to structure a conversation with their doctor about going on the medication: ‘OK, is this right for me or not?’”
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Using language that is meaningful to patients when discussing disease prognosis is a huge benefit for both clinicians and patients, said neurologist Dr. Richard Isaacson, director of research at the Institute for Neurodegenerative Diseases in Boca Raton, Florida. He was not involved in the study.
“However, these are not miracle drugs, so please keep that in mind,” Isaacson said. “All that happens is that people get less worse over time — instead of declining by three years, they decline by two years.”
Estimating ability to live without assistance
The study, published Thursday in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions, analyzed Washington University data on the natural progression of Alzheimer’s disease in 282 patients who had not been treated with medication.
“We looked at four different specific functions: Could the person pay their bills, drive a car, manage their own calendar and medications, and prepare their own meals?” Hartz said. “We defined the loss of independent living as needing assistance on at least three of those.”
The amount of time untreated patients spent living independently was used to create a timetable of decline. That trajectory was then compared with what was seen in patients using lecanemab and donanemab during each drug’s clinical trial.
A person with typical mild cognitive decline, such as forgetting appointments or being unable to follow conversations fully, could expect to live independently for 29 months without treatment, the analysis showed.
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Taking donanemab added eight months of independence, while taking lecanemab added 10 months, according to the calculations. While those additional months may not appear to be a long extension of independence, the estimates could be meaningful for some people, Hartz said.
“The drugs are very expensive, but once you compare that to the cost of a residential care facility or a nursing home, you might have a different perspective,” she said.
People with mild but obvious symptoms — such as repeating the same questions or getting lost — who already live in a residential facility also want to know when they will need additional, more expensive care, Hartz said.
At this stage of the disease, researchers estimated donanemab provided an additional 19 months of being able to dress, eat and bathe independently. Lecanemab provided 26 additional months of self-care.
“I want to stress that the purpose of this study was not to advocate for or against these medications,” Hartz said. “The purpose of the paper is to put the impact of these medications into context in ways that can help people make the decisions that are best for themselves and their family members.”
However, the analysis used in the study assumed changes in dementia scores “are linear and can be equated to changes in months of life. This has never been validated,” said Dr. Alberto Espay, a professor of neurology at the University of Cincinnati and director and research endowed chair of the university’s Gardner Family Center for Parkinson’s Disease and Movement Disorders.
“Further, ‘extension of independence’ means statistically longer time in the same state before further decline, not statistical improvement,” Espay said in an email. “This is important because patients cannot be counseled that they will improve if on treatment.”
Instead, he added, patients have to “hope that their decline will be slower than if they were not on treatment” while also hoping that they will not experience brain swelling or bleeding.
Concern with Alzheimer’s disease drugs
When the US Food and Drug Administration fast-tracked the approval of lecanemab and later donanemab, some doctors said they were skeptical whether the modest improvement seen in clinical trials was worth the risk.
Randomized controlled clinical trials found people taking lecanemab slowed their decline by 27% at 18 months compared with those who were not on the drug. That difference was about half a point on a commonly used scale to measure dementia progression.
People with mild cognitive decline on donanemab had about a 35% lower risk of progression over a year and a half compared with those who received a placebo.
However, the side effects could be brutal. Lecanemab can cause allergic reactions, confusion and dizziness, heart palpitations, muscle and joint pain, seizures, severe headaches, and flu-like symptoms, to name a few.
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Six deaths occurred among people taking lecanemab, and 2.8% of the participants in the drug trial experienced ARIA-E, or amyloid-related imaging abnormalities – edema, which involves bleeding and swelling in the brain, according to a report by doctors at Northwestern University’s Feinberg School of Medicine. No one who took a placebo experienced those reactions.
During the clinical trial for donanemab, 2.9% of those on the drug had a serious side effect related to ARIA-E, and three patients died, according to the Alzheimer’s Society. Nearly 13% experienced different serious side effects, the health organization reported.
To take the medications, patients must undergo regular brain scans to check for bleeding and swelling and be carefully monitored by their doctors.Due to an even larger risk of ARIA-E, both drugs are used with greater caution, if at all, for people with two copies of the APOE-4 gene, which indicates a genetic disposition for Alzheimer’s.
Treatments for Alzheimer’s are desperately needed, experts say. The number of people projected to have the disease is predicted to grow to nearly 14 million by 2060, according to the US Centers for Disease Control and Prevention. As of 2023, an estimated 6.7 million Americans 65 and older live with Alzheimer’s.
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