Alzheimer’s patients and their families hear a new word: Progress

When Dennis Carr learned he had early Alzheimer’s disease, he immediately thought of his older brother who had died of the illness in 2023.

“There was not much anyone could do,” Carr said of his brother’s long decline. “You could see him diminishing.”

Today, Carr is trying a new treatment called Leqembi that has been shown to modestly slow the disease for people in the initial stages of Alzheimer’s. Carr knows it is not a cure but he wants to buy time—to be with his family, to work and to give scientists a chance to find more solutions.

“I’m hoping this is the first steppingstone to something better,” said Carr, 74, an electrical contractor in Montgomery County, Pennsylvania.

Carr’s experience offers a glimpse of the shifting landscape of Alzheimer’s, a memory-robbing disease that affects more than 6 million Americans and is the seventh leading cause of death in the United States. Two new treatments, including Carr’s, target toxic clumps of a protein called amyloid beta in the brain and are the first to slow progression of the illness. Blood tests could revolutionize the way the illness is diagnosed. Lifestyle factors such as diet and exercise are showing promise in helping reduce the risk of cognitive decline.

“Progress against Alzheimer’s has been unprecedented,” said Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, a not-for-profit that funds the development of drugs and diagnostics. “But we have a long way to go.”

Two new drugs slow progression of Alzheimer’s

Doctors used to refer to Alzheimer’s as “diagnose and adios” because they had little to offer patients, said Adam Boxer, a neurologist at the University of California at San Francisco. “But now we see light at the end of the tunnel,” he said. “We might be able to have a big impact.”

Since January 2023, two new drug treatments—Leqembi made by Eisai and Biogen, and Kisunla made by Indianapolis-based Eli Lilly and Co.—have been approved by the Food and Drug Administration. Delivered intravenously, they are monoclonal antibodies, which are man-made proteins designed to bind to specific targets in the body. In this case, the drugs reduce amyloid clumps in the brain. In clinical trials the medications slowed cognitive decline by several months.

The therapies are controversial among some doctors, however, and prescribing has been less than robust. Some doctors say they don’t think the drugs provide big enough benefits to risk potentially life-threatening side effects such as bleeding in the brain.

The treatments are expensive: The list prices for Leqembi and Kisunla are $26,500 per year and $32,000, respectively. For now, it isn’t clear how long people should take Leqembi. The pivotal trial was 18 months long, but some people have been on the medication longer. Kisunla may be stopped after scans show amyloid beta has been cleared from the brain. And the medications can be used only in the early stages of disease.

In July, European drug reviewers recommended against the approval of Leqembi, saying its positive effects “do not counterbalance the risk of serious adverse events.” Eisai has asked for a reexamination of the review and said that Leqembi has been approved in the United States, China, Japan, Israel and several other countries.

Neurologist Jeffrey Maneval of Penn Memory Center defended the therapies. They are “a double, not a home run,” he said. “But you have to get on base.”

Pat Bishara, a 79-year-old Carmel resident, who received Kisunla from 2020 to July of this year as part of a clinical trial, said she is delighted with the results. Diagnosed with Alzheimer’s seven years ago, Bishara feels relatively stable. She continues to be able to play games and go shopping with her 11 grandchildren and has not experienced side effects.

“I can’t believe that it was 7 years ago that I was diagnosed,” Bishara said. “It has slowed down my progression, for sure.”

Researchers investigate drug combinations, vaccines

Even with recent progress, scientists say, a cure for Alzheimer’s could be years or decades away. But many experts agree on one point: To get better treatments for Alzheimer’s, researchers need to look beyond amyloid and develop drug combinations, as are used for cancer and HIV.

“Alzheimer’s is a disease that you have to throw the kitchen sink at,” said David C. Weisman, a neurologist at Abington Neurological Associates who treats Carr. “Each individual therapy has to bend the course [of the illness] a bit.”

Boxer of UCSF is preparing a major trial to test a combination of treatments that will target both amyloid and harmful tau proteins, which are linked especially closely to cognitive deterioration. Several companies are working on Alzheimer’s vaccines. Other researchers are testing the active ingredients in weight loss drugs and scrutinizing brain inflammation and vascular problems.

Miranda Orr, an associate professor of gerontology and geriatric medicine at Wake Forest University School of Medicine, is focusing on “zombie cells,” which are also known as senescent cells. Such cells have ceased to function but are not completely dead, causing damage to other cells. Orr is exploring whether eliminating zombie cells with a leukemia drug and another therapy could hinder the disease.

There is another idea researchers are testing in hopes of preventing the disease: If the new anti-amyloid treatments slow the course of early Alzheimer’s, could the therapies prevent memory loss and other problems entirely if given before people show symptoms?

A big international trial called AHEAD involves administering Leqembi to asymptomatic adults who are at high risk of developing the disease. These individuals typically have elevated amyloid in their brains, proved by special tests. The hope is that the anti-amyloid therapy will prevent memory loss from occurring. Kisunla is undergoing similar testing.

Blood tests might soon make diagnosis simpler

For decades, a definitive diagnosis of Alzheimer’s could be obtained only after death—by brain autopsies that showed accumulations of amyloid and tau. In recent years, gold-standard tools have emerged—brain scans called amyloid PET and cerebrospinal fluid samples obtained by spinal taps.

Those methods, however, are expensive and invasive and typically not used by primary care doctors who diagnose most Alzheimer’s cases. Those physicians generally rely on standard evaluation methods such as cognitive tests and CT scans. The rate of misdiagnosis is high.

Now new blood tests are on the cusp of providing a simpler and cheaper way to help diagnose the disease. Developed by several companies and academic institutions, the tests currently are used mainly in clinical trials but they are inching closer to clinical practice.

A study published this July in the medical journal JAMA reported that a blood test called PrecivityAD2 was able to determine whether memory loss was caused by Alzheimer’s 91 percent of the time as compared to 61 percent accuracy for primary care doctors and 73 percent for specialists using standard evaluation tools. The test, developed by C2N Diagnostics in St. Louis, detects proteins in the blood that indicate the likelihood of toxic plaques in the brain.

Some doctors say they want more data and even better results before adopting blood tests. In addition, none of the tests has been approved by the Food and Drug Administration or is paid for by Medicare.

Still, experts say, the tests eventually are likely to become part of the assessments used to help diagnose people with memory issues. The tests should not be used at this point to screen “the worried well” without symptoms, experts say. That’s because there are no treatments available for people who are asymptomatic but test positive for Alzheimer’s biomarkers.

Lifestyle hacks can mitigate cognitive decline

While treatments are critical, the Holy Grail for Alzheimer’s advocates and researchers is preventing the disease. There is no proven method to do so. But brain changes occur years before symptoms emerge so there is at least a theoretical possibility of improving brain health and preventing cognitive decline, scientists say. Increasingly, studies are pointing to lifestyle changes that can reduce the risk of developing the disease or delay its onset.

A landmark Finnish study called FINGER found five lifestyle measures were especially beneficial: a diet with ample vegetables, whole grains, beans and fish; physical activity; mental stimulation; social activities and control of cardiac risk factors such as blood pressure and cholesterol. An updated version of the 2015 trial is adding the older diabetes drug metformin to see if the results are even stronger. Diabetes is a known risk factor for Alzheimer’s.

Other helpful steps include correcting hearing and vision loss, sufficient sleep, quitting smoking and avoiding excessive drinking, according to several studies. Citing such “modifiable” risk factors, the Lancet Commission on dementia has said about 45 percent of cases of dementia worldwide “are potentially preventable.”

For Pat Bishara, the progress against Alzheimer’s is worth talking up. Once too embarrassed to admit she has the illness, Bishara now urges others with memory problems to undergo testing and get treatment. “Don’t be embarrassed,” she said. “Don’t be ashamed.”