By Laura Freeman

Early diagnosis of Alzheimer’s Disease has just become more urgent.

“Now that we have a therapy that can slow the progression of Alzheimer’s Disease (AD) by 25 to 35 percent, we can finally do something to delay the damage,” said David Geldmacher, MD, FACP,  neurologist and director of UAB’s Division of Memory Disorders and Behavioral Neurology.

Clinical trials conducted at UAB gathered evidence that led to the accelerated limited approval of Lecanemab, commercially known as Leqembi, in January. Further trials confirmed the effectiveness of the drug in slowing progression when administered to patients early in the course of the disease. That led to the Leqembi becoming the first new AD therapy to receive full FDA approval in 20 years.

This approval has also opened the door to Medicare coverage of the medication, with the provisions that patients must be in the early stages of AD, and they are required to participate in a registry that will continue to track the benefits of the drug and its safety.

“The drug is a protein antibody that binds to amyloid plaques and is administered as an infusion in a healthcare setting every two weeks for 18 months,” Geldmacher said. “About 26 percent of patients may benefit from over-the-counter Tylenol or Benedryl if they experience a typical mild infusion reaction. After 18 months of treatment, PET scans show that most of the amyloid protein has been removed.

“We aren’t yet sure where or when the drug antibodies bind to the amyloid proteins, but it may be in the bloodstream. We hope the amyloid protein won’t return and that the time gained while using the drug will continue to push forward the progression of worsening symptoms to a time later than they would have appeared.

“This medication is a treatment, but not a cure. It doesn’t reverse damage to neurons that have already been compromised, so unfortunately it isn’t for patients whose symptoms have progressed to the point they are no longer independent. The drug is aimed at plaques, but it doesn’t address the tangles that are already there. We don’t know yet how reducing amyloid plaques will affect the formation of tangles, which are the other half of the equation in progression of the disease.

“Our goal with this medication is to give patients more time to live independently and enjoy being with their family and friends. We want to delay the need for a caregiver, and give families more time to live without the burden and expense of caregiving. ”

The drug is continuing to be studied in hopes of improving it. Researchers are working on a form that could be self-injected much the same as insulin. Other drug companies are working on medications with a similar mode of action. Eli Lily is developing a medication that we think is likely to be approved this year.

It’s always good to have multiple options, since a patient who may not be a candidate for one drug could possibly benefit from another,” Gelmacher said. “I should add that Leqembi shouldn’t be given with a blood thinner, since a small percentage of patients have experienced side effects of small brain bleeds or swelling. The swelling usually resolves and the bleeds are sometimes so slight they only show up on imaging, but it is enough of a concern to make blood thinners a contraindication. These rare side effects seem to be more likely to occur in patients with an APOE-4 variant, so those with that genetic profile should be closely monitored.”

Additional research is underway to develop drugs that target the formation of tangles. New uses of drugs already approved for other applications are also being studied to see if they might benefit Alzheimer’s patients.

“One area with a great deal of potential is drugs for diabetes, including those that are now being used to help with obesity,” Gelmacher said. “There is something about insulin resistance that seems to be involved in the development of AD.

“Since Alabama has the third highest death rate from Alzheimer’s Disease in the nation, every step forward really matters to the people all around us.

“The takeaway for physicians and other health professionals is that we need to watch for indications of possible Alzheimer’s Disease every time we encounter patients who may be at risk. In the past, there was a social tendency to avoid bringing up the possibility of a memory disorder until it became obvious. Now we can make a real difference in the course of the disease and the quality of patients’ lives, but to get the full benefit, we have to start early.”