How Is Alzheimer's Disease Treated? Experts Discuss Current Options—Including One New Promising Drug
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Alzheimer’s is an irreversible, progressive disease that touches almost every family and every community in America. The disease—which causes memory loss, confusion, personality changes, and eventually, death—affects an estimated 6.2 million Americans over age 65. As the population ages, that number is expected to rise to nearly 13 million by 2050. About two-thirds of people with Alzheimer’s are women, and the risk is greater for older Black and Hispanic Americans than for older white Americans.
The heart-wrenching truth about Alzheimer’s is that right now there is no cure, but there are some treatment options available that can help manage some of the worst symptoms of the disease. The Food and Drug Administration (FDA) recently approved the first new medication in decades (aducanumab), which is also the first one to address the underlying pathology of the disease rather than simply treating the symptoms. But that drug is not without controversy, and so far it has reached very few patients.
The other medications that are available can only treat the symptoms of Alzheimer’s, and they only work for a limited amount of time, says Rebecca M. Edelmayer, Ph.D., senior director for scientific engagement for the Alzheimer’s Association. But there are promising trials going on in labs all over the world, as scientists race to find a way to slow down or even prevent the disease. “There is an amazing amount of work going on in this field and there is a lot of space for hope,” Edelmayer says.
What is Alzheimer’s disease?
Alzheimer’s is the most common type of dementia, accounting for between 60 and 80% of those who are suffering from memory loss and cognitive decline that is not due to typical aging. Though there is still a lot to learn about the disease, we know that it involves changes in the brain, including shrinking, blood vessel damage, and most crucially, the development of protein deposits known as plaques and tangles: Plaques, which are made up of beta-amyloids, clog the area between nerve cells, while tangles, which are twisted fibers of the tau protein, accumulate inside the cells. Both interfere with the ability of neurons to talk to each other, and they eventually cause brain cells to die.
These changes in the brain can begin years before the person notices anything unusual is going on. In the earliest stage of the disease (known as mild cognitive impairment), the most common symptom is not being able to remember new information—the individual may ask the same questions over and over again, get confused with simple directions, lose track of household items, and more.
What are Alzheimer's treatment options?
In addition to the newly approved aducanumab, there are five other FDA-approved medications to treat the cognitive symptoms of Alzheimer’s. “These medications can’t reverse or stop the progression of Alzheimer’s, but what they can do is turn up the volume between the brain cells so they can communicate better,” Edelmayer explains. She also points out that patients see the most benefits when these medications are taken at the earliest stages of cognitive decline. “An early and accurate diagnosis is really important,” she says. “The biology of it is that you may not see as much benefit later, when the cells that it is meant to work on no longer exist in the brain.”
These treatments fall into two categories:
Cholinesterase inhibitors
These medications work by preventing the breakdown of acetylcholine, a brain chemical that is believed to be important for memory and learning, and they are mainly used in the early and moderate stages of Alzheimer’s. As the disease progresses, the brain produces less and less acetylcholine, meaning the inhibitors have nothing to work on. The FDA-approved drugs in this category include:
Aricept (donepezil), for all stages
Exelon (rivastigmine), for mild to moderate Alzheimer’s as well as for dementia-related to Parkinson’s disease
Razadyne (galantamine), for mild to moderate Alzheimer’s
Glutamate regulator
This drug works by blocking the toxic effects of a brain chemical called glutamate, excess amounts of glutamate can lead to the death of brain cells. It is available in:
• Namenda (memantine), for moderate to severe Alzheimer’s
Combined medication
Because cholinesterase inhibitors and glutamate regulators work differently, they can be prescribed together, and in fact, there is one FDA-approved drug that combines both therapies:
• Namzaric (memantine and donepezil), for moderate to severe Alzheimer's
Whichever medication is prescribed, doctors will usually start the patient on a low dose and increase the amount based on how well they tolerate the drug (side effects may include nausea, fatigue, loss of appetite, constipation, and headache). “Sometimes there will be a mild improvement right away, in terms of being able to recall memories that the patient wasn’t remembering before,” says Elise Caccappolo, Ph.D., an associate professor of neuropsychology at Columbia Irving Medical School. “It’s a little bump that usually lasts around six months, and then they usually plateau,” she explains.
What other medications may help?
Along with memory loss and confusion, individuals with Alzheimer’s can also experience behavioral and mood problems, including insomnia, agitation, aggression, and even hallucinations. “Today, we still do not have any therapeutics that specifically treat behavioral and psychological features in people with Alzheimer’s,” says Edelmayer. “We have medications that are approved for the general population, but they have not been tested in individuals with dementia.”
In many cases, physicians will recommend non-medical treatments first, such as lifestyle changes and cognitive behavioral therapy, before moving on to medications such as antidepressants and antipsychotics such as Seroquel (to treat aggression and hallucinations), which may have serious side effects for people with Alzheimer’s.
Edelmayer points out that one medication, suvorexant (Belsomra), has been tested and approved for insomnia in people with Alzheimer’s, and other medications for dementia-related psychosis, agitation, and apathy are currently in phase 3 trials, getting close to the finish line of FDA approval.
Which drug did the FDA recently approve?
On June 7, 2021, the FDA announced its approval of aducanumab (produced by Biogen under the name Aduhelm), a monoclonal antibody that is administered through an IV infusion once every four weeks. This is the first new Alzheimer's medication the FDA has approved since 2003, and it is the first drug that claims to slow down the actual process of Alzheimer's in people with mild cognitive impairment, which it does by reducing the production of beta-amyloid plaques in the brain. "This approval is a victory for people living with Alzheimer’s and their families,” said Harry Johns, president and CEO of the Alzheimer’s Association, in a statement. “This is the first FDA-approved drug that delays decline due to Alzheimer’s disease."
While the news has been embraced by many in the Alzheimer's community, who welcome the first ray of hope after decades of promising drug trials that ended in disappointment, many researchers in the field—including an independent advisory panel that the FDA tasked with evaluating the data—believe the drug has not proven that its efficacy outweighs the risks (which may include temporary swelling and bleeding in the brain).
The treatment is not cheap—it costs roughly $56,000 per year—and the individual is required to undergo regular MRIs to check for swelling in the brain, at an additional cost.
The FDA approved aducanumab through its Accelerated Approval Program, which is used to fast-track the use of new drugs for devastating diseases that have few other treatments. As part of this approval process, Biogen is required to conduct additional clinical trials over the next few years; if it cannot sufficiently prove the drug's efficacy, the FDA may withdraw its approval.
"There is a lot of debate about whether or not this drug is going to make the clinical difference we've all been longing for," says James Noble, M.D., an associate professor of neurology at Columbia University Irving Medical Center. "I think many of us in the field see this as the first step towards a new treatment landscape, but not necessarily the one that's going to change the course for everyone that dramatically." According to one recent report, as of September, 2021, only 100 patients had been treated with the drug; several prominent hospitals have declined to offer the controversial drug to patients.
What treatments are in the pipeline for Alzheimer's?
There are hundreds of clinical trials going on right now, in which scientists are exploring many different pathways toward diagnosis, treatment, and prevention of Alzheimer's, says Edelmayer. “There are a number of different types of therapeutics being evaluated,” she explains. “Some change the progression of the disease and some lessen the symptoms—we need both approaches going forward.” Some promising areas of research involve vaccines that prevent tau proteins from forming and drugs that reduce inflammation in the brain.
"One of the biggest hurdles in making progress is recruiting and retaining patients for these trials," Edelmayer adds. "We especially need more diverse people, including those from underrepresented populations." (Go to the Alzheimer's Association's TrialMatch page to find which trials you or your family member may be eligible for.)
What lifestyle changes can help?
Piles of research over the last few decades have shown that lifestyle factors can have a big impact on the development of Alzheimer's symptoms. "We are looking not only at therapeutic treatments, but also at how modifiable factors, such as a heart-healthy diet, exercise, health equity, and social engagement can reduce risk the risk of Alzheimer's," says Edelmayer. The U.S. POINTER Study is currently evaluating whether lifestyle interventions that target Alzheimer's risk factors can protect cognitive function in older adults who are at risk for cognitive decline. Meanwhile, the following activities are believed to lower risk and delay the symptoms of dementia:
Physical exercise: Regular exercise can improve blood flow to the brain and increase the volume of the hippocampus, keeping the brain healthy longer.
Brain-healthy diet: Research has found that eating a Mediterranean, MIND, or DASH diet can decrease oxidative stress and inflammation and accumulation of beta-amyloids in the brain, decreasing the risk of Alzheimer's.
Social engagement: Several studies have concluded that staying connected to family and friends appears to have a protective effect on the brain. Volunteering, participating in support groups, joining book clubs, and doing other regularly scheduled social activities can also keep your brain active and healthy and may delay the onset of dementia.
Mental stimulation: Learning a new skill, completing puzzles, working on crafts, and playing games that make you think strategically may help keep your cognitive skills sharp.
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