David Geldmacher, MD, professor of neurology and director of the Division of Memory Disorders and Behavioral Neurology at the University of Alabama at Birmingham.
Although there are some approved medications for Alzheimer’s disease (AD), nothing has ever been able to slow down the relentless progression of the disease until now.
AD is an irreversible and progressive brain disease that slowly destroys memory and thinking skills (called cognitive skills) and the ability to carry out simple tasks. While the exact cause of AD is unknown, part of the problem is believed to be changes in the brain caused by a buildup of an abnormal protein in the brain called amyloid. Amyloid forms into toxic plaques that gradually strangle brain cells.
The new drug is called lecanemab (Leqembi). It is a member of a new family of drugs called anti-amyloid monoclonal antibodies. A monoclonal antibody is a protein created in a lab. Anti-amyloid antibodies are designed to bind to amyloid proteins in the brain and prevent them from becoming toxic plaques.
The Lecanemab in Early Alzheimer’s Disease trial was presented at the 2022 Clinical Trials for Alzheimer’s Disease Conference in November, and also published in The New England Journal of Medicine. Based on this trial, the FDA granted accelerated approval for Leqembi in January 2023 for patients with early AD and mild dementia.
This was a placebo-controlled, double-blind study, which means that patients were randomly assigned to receive an inactive placebo or Leqembi. Neither the patients nor the researchers knew who got a placebo or the drug. This type of trial is the gold standard for drug approval.
The trial was conducted at 235 sites in the United States, Europe, and Asia. There were 1,795 patients in the study. They included 898 patients in the drug group and 897 in the placebo group. All the patients were diagnosed with early AD based on dementia symptoms on the clinical dementia scale, the finding of amyloid on a brain imaging study (PET scan), and an AD assessment of daily living scale. After 18 months, these were the key findings for patients taking the drug versus placebo:
Commenting on the results of the study, Dr. David Geldmacher, professor of neurology and director of the Division of Memory Disorders and Behavioral Neurology at the University of Alabama at Birmingham, said, “Lecanemab is the first drug to slow the progression of Alzheimer’s disease in a very robust clinical study.” Dr. Geldmacher was at the conference and participated in the clinical investigation that led to the lecanemab trial.
An important part of the trial and the FDA approval was safety. The most common adverse events were an infusion reaction causing headaches and flu-like symptoms, and a condtion called amyloid-related imaging abnormalities (ARIA). ARIA abnormalities include small areas of bleeding (microhemorrhages) and accumulation of fluid in the brain (brain effusions). ARIA is usually temporary and does not cause symptoms, but, rarely, it can be dangerous, causing confusion, dizziness, vision changes, nausea, or seizures. Overall adverse events were 13 percent more common in the drug than the placebo group.
According to the Alzheimer’s Association, “The results of the trial show that this treatment may change the course of early AD in a meaningful way and give people more time to remain independent and participate in daily life.”
A newer and possibly better anti-amyloid antibody is in the clinical trial pipeline. It’s called donanemab. Early results are encouraging. We should have full results in 2023 or 2024.
There are two other types of drugs that are approved for use in AD. These drugs can help control some of the early symptoms of AD.
Cholinesterase inhibitors work by increasing communications between brain cells by getting the most out of brain cells that are still healthy. They inhibit the breakdown of a chemical messenger that eventually gets depleted in AD. Cholinesterase inhibitors work best in early AD and may be the first medications used. They may reduce AD symptoms like depression, anxiety, and agitation. Common brands are donepezil (Aricept) and rivastigmine (Exelon). Side effects can include diarrhea, nausea, and loss of appetite.
The other type of drug, memantine (Namenda), also attempts to make the best of what is still working in AD, but it works on different brain cells and may be effective longer as AD progresses. Side effects include dizziness and confusion. The two drugs are sometimes used together. Although they can reduce early symptoms, they do not delay progression to more advanced disease.
Yes. According to the U.S. Centers for Disease Control and Prevention (CDC), healthy aging may reduce your risk by about 40 percent. You can reduce your risk by being mentally active. Mental activities like learning a new skill, reading, doing brain teasers, and being socially active build cognitive resilience. That means that even if you have some early AD, you have built up enough brain power to combat it. Autopsy studies show that some people have significant AD in their brains but never develop symptoms of AD, due to cognitive resilience. The CDC says these other eight lifestyle changes can help reduce AD risk: