New Alzheimer's medication

The U.S. Food and Drug administration granted traditional approval of Leqembi (lecanemab) for the treatment of early Alzheimer's disease. While it's not yet a cure, it apparently slows the progression of symptoms. Since the medication needs to be started early during the course of the disease, should older individuals like me (77) have some form of screening for Alzheimer's? This might pick up the disease before the patient, family and physician become aware of it, so treatment could be started at the earliest time.

— D.S., M.D.

Lecanemab is a new treatment for Alzheimer's disease. It is a monoclonal antibody against the amyloid protein. Amyloid protein is found in the brains of people with Alzheimer's disease, and it is hypothesized that amyloid protein may be part of the underlying cause of Alzheimer's, although a second protein, tau, may also have a role.

There is considerable interest in lecanemab since a 2023 trial showed that it slowed the worsening of cognitive loss compared to a placebo. Lecanemab essentially stopped the deposition of amyloid protein, even reducing the amount present in the brain.

There are some important cautions. The first is that the drug, given intravenously twice a month, is only indicated in people who are proven to have amyloid protein in the brain and who have early Alzheimer's disease or mild cognitive impairment by formal testing. It is not for use in people with no symptoms or those with advanced dementia.

Amyloid positivity has traditionally required a PET scan or evaluation of cerebrospinal fluid from a lumbar puncture (spinal tap), although a new blood test (the beta-amyloid 42/40 ratio) seems to be able to predict Alzheimer's.

The second caution is that there are toxicities to the treatment. One serious toxicity is a class of brain swelling called ARIA (amyloid-related imaging abnormalities), which happened in 22% of lecanemab subjects, compared to 10% of placebo subjects. Brain MRI scans are recommended during treatment to look for ARIA.

Finally, although the drug was successful at removing some amyloid protein, its effect on brain function in this early study was disappointing, with only a modest slowing (about 27%) in the progression of the disease, rather than stopping or, better yet, reversing the damage. This suggests that amyloid protein deposition may not be the critical issue in the underlying cause of Alzheimer's disease. Furthermore, it has only been studied for 18 months, and it is quite expensive, with the manufacturer charging $26,000 per year for treatment.

Since the drug, as of yet, has not been proven to have a dramatic effect on the course of Alzheimer's, my personal opinion is that widespread screening for the purpose of early treatment with this drug is not a high priority.

Screening for dementia is important, and physicians should have a discussion on the treatments that have been shown to reduce dementia risk, specifically dietary treatment and moderate exercise, as well as cognitive training. People with high blood pressure or diabetes benefit from careful control of these conditions. It is disappointing, but medications, including supplements and prescription medicines, have not had a big impact on Alzheimer's disease so far. But it is possible that this drug or similar ones will be better with further study.

Contact Dr. Roach at ToYourGoodHealth@med. cornell.edu.

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