Alzheimer’s treatments enter a new era

Tim Sandry has an early form of Alzheimer’s disease, but considers himself fortunate to have started treatment with a promising new drug.

“If there is a chance this will slow the progression, that’s the best I can hope for at the moment,” said the 67-year-old Bloomington retiree.

While there’s still no cure, breakthrough research and new therapies are providing newfound hope to patients and their caregivers. Nearly 7 million Americans live with Alzheimer’s, including over 100,000 in Minnesota. The national number is expected to double by 2060, according to the Alzheimer’s Association.

As the U.S. population ages, the research race is on to find ways to diagnose the disease earlier, slow its progression and perhaps prevent it.

“It’s an exciting time to be involved in Alzheimer’s research and caring for patients because now we have something we can talk about with patients,” said Dr. Ronald Petersen, director of Mayo Clinic’s Alzheimer’s Disease Research Center in Rochester.

“We definitely are in a new era,” said Joseph Gaugler, the Robert L. Kane Endowed Chair in Long-Term Care and Aging at the University of Minnesota’s School of Public Health. “These new class of therapeutics are far more promising than in the past [and] we have new diagnostic techniques that will be more widely available.”

Alzheimer’s is the most common form of dementia, accounting for about two-thirds of all cases. While the disease is more common in people age 65-plus, it can develop in people as young as in their 30s.

The fatal disease worsens over time, affecting parts of the brain that control memory, speech and thinking. It’s believed that damage to nerve cells (neurons) in the brain causes Alzheimer’s, but exactly why and how remains a mystery.

An Alzheimer’s treatment from idea to market can take up to 20 years. After a long hiatus, the U.S. Food and Drug Administration (FDA) has approved three new drugs to treat Alzheimer’s since June 2021.

While most early treatments focused on treating Alzheimer’s symptoms, research has turned more to the disease’s underlying biology to create targeted therapies to slow or stop its progression. Some of the most common Alzheimer’s drugs in development aim to prevent or remove the buildup of harmful proteins in the brain, target inflammation and help neurons in the brain communicate better to aid body function.

“The main implication of these drugs is how early can we go,” Petersen said. “Can we detect cognitive issues in the brain earlier and delay the onset of Alzheimer’s?”

Here’s some of the new research and treatments for Alzheimer’s.

Traditional diagnostic methods like a spinal tap or imaging tests can be difficult for some Alzheimer’s patients. New noninvasive, less expensive methods detect Alzheimer’s before symptoms arise, enabling patients to start preventive measures.

In July, researchers unveiled a blood test that can detect Alzheimer’s hallmark brain changes. A Swedish study found the test was 90% accurate in identifying Alzheimer’s in patients with cognitive symptoms.

Limited blood tests are available now, but researchers and doctors think they’ll be more widespread within a year. “It’s not inconceivable that in the near future we’ll be able to do a blood test in a doctor’s office,” with a cognitive screen along with testing for glucose and cholesterol, Petersen said.

Last year, other researchers developed a portable diagnostic test that uses an electrical sensor to detect biomarkers for Alzheimer’s before symptoms show. They’re testing whether the device could eventually work in home settings.

Abnormal amounts of beta-amyloid proteins (called plaques) and twisted fibers of tau proteins (called tangles) accumulate in the brains of people with Alzheimer’s. Amyloid plaques damage and destroy neurons in the brain. Tau tangles attack their synaptic communications, which controls body functions like muscle movement and memory.

Much excitement surrounds two new drugs with full FDA approval that slow the Alzheimer’s progression by reducing or removing amyloids — lecanemab (brand Leqembi) approved in July 2023 and donanemab (brand name Kisunla), approved this July. Donanemab is the first drug to delay the effects of mild cognitive impairment, an early form of Alzheimer’s, but treatment hasn’t started yet. A third drug, aducanumab (brand Aduhelm, approved in June 2021) will be discontinued in November.

In an 18-month clinical trial, lecanemab slowed cognitive and functional loss by 27% in people with mild cognitive impairment or Alzheimer’s-related mild dementia.

“That’s quite incredible,” said Rebecca Edelmayer, vice president of scientific engagement for the Alzheimer’s Association national office. “In the past, we only had treatments that would go after symptoms — temporarily relieving these symptoms.”

Lecanemab can cause brain swelling and micro bleeding, which can be serious in rare cases, so doctors perform regular brain scans to check.

Soon after Sandry began lecanemab intravenous infusions, an MRI test showed a small brain bleed, so treatments stopped for a while. Since he’s resumed bi-weekly infusions, regular scans show no further bleeding.

While the experience was scary, Sandry, who was diagnosed earlier this year and started treatments not long after, said the potential benefits are worth the risk.

“What the drug does is slow the progression so my wife and I have a bit more time while I’m still functional,” he said. “I’ve adopted a one-day-at-a-time approach.”

Kanada Yazbek of Ramsey, who has lived with mild cognitive impairment for 10 years, still is waiting to see if she qualifies for lecanemab treatments. “My hope is that we continue to have preventions that come from research,” she said.

The AHEAD Study is testing whether lecanemab can prevent tau formations in the brain with even earlier treatment to slow cognitive loss by more than 27%, said Dr. Jonathan Graff-Radford, a neurologist at Mayo Clinic in Rochester and principal investigator of AHEAD there. It and Mayo’s Jacksonville location are among 70 sites nationwide.

Some studies hope to block several proteins toxic to the nervous system.

Dr. Dongming Cai, a professor of neurology at the University of Minnesota and director of its N. Bud Grossman Center for Memory Research and Care, is focused on finding non-amyloid pathways and treatments to address inflammation and neurofunctions. “In our bodies, we have toxins that build up and we try to clean them up like a garbage disposal system,” she said. “What we’ve found in people with Alzheimer’s is that this garbage disposal system doesn’t work well.”

Cai hopes to find an oral novel drug that would help this process and make it “much safer so a patient can take it every day to help their memory, slow the progression of the disease or prevent the development of Alzheimer’s in the first place,” she said.

One big trend is trying to find benefits to Alzheimer’s patients from existing drugs designed for other purposes. Researchers think so-called GLP-1 drugs like Ozempic and Wegovy, which have helped people lose weight, manage diabetes and reduce the risk of heart disease, may help fight Alzheimer’s by protecting the brain.

How? These drugs reduce inflammation and blood sugar, which are linked to Alzheimer’s.

In July, researchers in London released a study showing that a diabetes GLP-1 drug called liraglutide appears to slow cognitive decline by as much as 18% after one year.

In St. Paul, William H. Frey II, research director for HealthPartners Institute’s Neuroscience Research Center, is studying the use of a noninvasive intranasal delivery method he discovered in 1989 to treat Alzheimer’s with deferoxamine, a drug that’s been used to reduce iron overload from sickle cell disease and blood transfusions. Deferoxamine can prevent memory loss, he said.

“We know there’s an excess of iron accumulation in the brains of people with Alzheimer’s,” said Frey, whose long-time partner has Alzheimer’s. “My hope is that by using this iron-binding drug we’re going to reduce oxidated damage in the brain to important receptors, like those involved in memory and movement.”

Lab tests in animals have been promising, and he hopes to start human clinical trials within three years.

It’s increasingly thought that multiple factors cause Alzheimer’s. And Alzheimer’s patients often suffer from other health conditions. So, research “is moving toward multiple targets or combination therapies to potentially treat multiple parts of the Alzheimer’s disease physiology,” said Graff-Radford.

Some new studies target amyloid and tau proteins simultaneously to see if Alzheimer’s progression can be slowed further. And the global evoke+ study is examining the potential of a GLP-1 drug to help early Alzheimer’s patients and those who also have vascular problems, Graff-Radford said.

The number of inflammation-related projects administered and funded by the NIA in the past 10 years has increased nearly five-fold from the prior 10 years. Brain inflammation is thought to play role in causing Alzheimer’s.

Alzheimer’s researchers at the University of Kentucky are focusing on drugs that may keep immune cells in the brain from overproducing inflammatory chemicals that damage neurons and their communications.

“There’s a need for those different unique approaches,” Edelmayer said. Future treatments “will be a combination of very effective therapeutics and it will very likely include lifestyle changes that have worked well with cancer or cardiovascular diseases. That’s really where the field is going for the future.”

More Alzheimer’s-related research projects and funding are paving the way for what scientists and doctors foresee as even bigger Alzheimer’s developments over the next decade.

The National Institute on Aging (NIA), for example, is funding 507 active clinical trials on Alzheimer’s, related dementias and caregiving, up from 229 five years ago.

And 2023 marked the first time the Alzheimer’s Association funded $100 million of research in one year, noted Susan Parriott, CEO of the Minnesota-North Dakota chapter. Today, the association is funding 1,100 projects worldwide, including $3.9 million in 10 projects in Minnesota, she said.

“We’re getting up to the level of cancer and stroke research [funding],” Parriott said. “We’re going to be able to learn so much more about what is the next big thing to study. "

Blaine resident Carolyn Oldani is optimistic about where Alzheimer’s research is headed — even though it won’t help her husband Carl, who died of Alzheimer’s in 2022.

When he was diagnosed in 2015, “it felt like it was a death sentence,” said Oldani, 63, who quit her executive-level job to care for Carl. “Going on 10 years later, it feels good that we’re seeing some really exciting developments to slow the progression. For the first time, it feels like [a cure] is within reach for the current generation even if it was too late for him.”