For anyone who has or knows someone who has Alzheimer’s disease, a progressive and irreversible form of dementia that’s ultimately deadly, it can sometimes be difficult to find hope.
A progressive, neurodegenerative brain disease, Alzheimer’s affects memory and cognitive functions including problem-solving, orientation, language and visual spatial skills, which eventually lead to functional problems that interfere with the person’s ability to perform daily activities such as driving and managing finances. In severe cases, basic activities of daily life — such as dressing, walking and eating — also become difficult.
In addition to cognitive problems, Alzheimer’s disease can also bring on a range of behavioral and emotional changes, including:
— Depression.
— Anxiety.
— Irritability.
— Delusions.
— Changes in sleep or appetite patterns.
Alzheimer’s is the sixth leading cause of death among U.S. elderly, accounting for more deaths than breast and prostate cancer combined. The disease continues to affect more and more people, with a new diagnosis made every 65 seconds. Currently, there are approximately 6.7 million Americans over the age of 65 living with Alzheimer’s.
There’s no cure for Alzheimer’s, but new drugs to treat the disease have recently garnered a lot of attention and controversy.
Recent Alzheimer’s Drug Treatments
Two drugs have received the Food and Drug Administration’s approval for use in Alzheimer’s treatment through the federal agency’s accelerated approval pathway, which is used for drugs that are intended to treat serious or life-threatening illness if the medication has demonstrated to provide a significant therapeutic advantage over current available treatments. The drugs, aducanumab (Aduhelm) and lecanemab (Leqembi), were approved in June 2021 and January 2023, respectively.
Both drugs were developed by pharmaceutical companies Biogen and Eisai, and they target the same specific cause of Alzheimer’s symptoms.
In July 2023, lecanemab received full approval from the FDA, which is a step up from its previous approval. Biogen notes that it is “the first and only approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline in adults with Alzheimer’s disease.”
The drug received this level of approval after the FDA’s review of studies that showed that use of lecanemab significantly improved cognitive and functional capabilities in adults with Alzheimer’s. The study looked at a variety of functional capabilities, including peoples’ abilities to dress and feed themselves and participate in community functions.
While both drugs received the FDA’s fast-tracked approval, aducanumab is no longer available for those with Alzheimer’s disease. In January 2024, Biogen decided to stop the current aducanumab clinical trial and discontinue their development and commercialization of the drug. According to the company’s press release, the decision was “not related to any safety or efficacy concerns.” Instead, they will be refocusing their efforts on lecanemab and other treatment methods.
[READ: Which Doctor Should I See for Dementia and Cognitive Decline? ]
Lecanemab and Aducanumab for Alzheimer’s
Both drugs were created with the intention of slowing the cognitive decline of people with Alzheimer’s and both target amyloid plaques in the brain.
Amyloid protein builds up into tangles, called amyloid plaques, in the brains of people with Alzheimer’s disease. It’s believed that the spread of this sticky protein in the brain causes Alzheimer’s disease to advance.
How lecanemab works
Lecanemab is delivered via IV infusion every two weeks.
“Lecanemab affects the plaque formation and actually removes plaques from the brain,” explains Dr. Ronald Petersen, director of the Mayo Clinic‘s Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging. “The newest drugs that are being evaluated now all have the properties of lowering the amyloid plaque level in the brain, and — presumably — that’s why they’re effective.”
How aducanumab works
Aducanumab was “the first approved disease-modifying treatment aimed at removing amyloid protein from the brain,” says Dr. Douglas Scharre, director of the division of cognitive neurology at the Ohio State University’s Wexner Medical Center in Columbus, who helped test the drug.
While it was the first approved drug, its production and further research have been halted by Biogen, who licensed the drug from the Switzerland-based biotechnology company Neurimmune. The drug licensing rights will now revert to Neurimmune, and Biogen will instead focus its efforts on lecanemab trials and commercialization.
How they differ
Since Biogen’s decision to stop the clinical trial and commercialization efforts of aducanumab, lecanemab is now the only FDA-approved drug that will be available to those with Alzheimer’s disease.
While both drugs are similar, Petersen notes that they are slightly different in how they reduce amyloid plaque levels.
“At the 10,000 foot level, they look like they’re targeting the same entity, but they are in fact different,” he says. “The drugs really interact at different molecules in the amyloid processing sequence.”
This means that, while plaque reduction on a PET scan is similar, the actual molecular action of the drugs may be somewhat different and, therefore, may lead to different side effect rates.
[READ: 5 Signs It’s Time for Memory Care.]
Serious side effects
Dr. Mariatu Koroma-Nelson, medical director of Goodwin House Incorporated, a not-for-profit senior living community based in Alexandria, Virginia, says that aducanumab has been associated with the following serious side effects:
— Cerebral edema (swelling of the brain).
— Confusion.
— Brain bleed.
— Increased risk of falling.
According to a 2022 article published in the Journal of the American Medical Association Internal Medicine, side effects, and particularly dangerous ones, weren’t uncommon. While only 1% to 2% of patients were hospitalized or impaired, 41% of patients in the aducanumab trials and 12.6% of patients in the lecanemab trials experienced some degree of brain swelling or bleeding.
Petersen, who was not involved in any of these drug trials, says that these side effects are something people have to be aware of.
“You cannot ignore it,” Petersen says. “These are potentially serious side effects, but I think the rate is relatively low and they are largely manageable.”
He adds that a percentage of this swelling and bleeding in the brain was caused by microhemorrhages, which are tiny ruptures of small blood vessels, and is asymptomatic. They can only picked up on MRI scans that were part of the study process.
While there were three deaths due to lecanemab identified in published case reports, each case was due to extenuating circumstances, Petersen adds. One of the patients was on a blood thinner medication for atrial fibrillation, and the other had a stroke that was treated with a clot buster in the emergency room. That additional medication may have broken up the blood clot causing the stroke, but also caused a serious brain bleed that led to the patient’s death.
But, Petersen says, he thinks that for the most part, these side effects can be managed with appropriate recommendations that will be developed to determine whether lecanemab should be used with blood thinners or whether people on lecanemab should be getting regular MRI scans.
[READ: Homecare for a Loved One With Alzheimer’s or Dementia.]
Cost of New Alzheimer’s Drugs
Other issues that have been cited by some experts include the possibly prohibitive price tag: lecanemab’s price has been set at $26,500 per year.
However, the Center for Medicare and Medicaid Services (CMS) recently announced that they will provide coverage for lecanemab. This means that original Medicare enrollees will pay the 20% coinsurance required by Medicare, in addition to the cost of their annual deductible. Unless a patient has a supplemental Medicare plan, they will still need to pay more than $5,000 per year for treatment with lecanemab.
The Problem With Alzheimer’s Treatments
Cost isn’t the only barrier to accessing Alzheimer’s treatments. Prescribing physicians will also need to register patients in the CMS registry for the drug. Physicians will be required to perform regular physical and mental exams to ensure that patients aren’t having adverse responses to treatment. Petersen says that follow-up for this sort of new drug is important, but he’s concerned that this registry requirement will limit use of the drug and might increase existing health disparities.
“What CMS has done is laudable, meaning that they have made it a ‘light touch’ registry that probably only takes minimal effort on the part of the clinician. Nevertheless, for a busy, practicing clinician — particularly one who may be accessible by underrepresented groups — it’s another hurdle,” Petersen says.
Petersen is concerned that people in underrepresented communities may not have access to physicians who feel comfortable or have the resources to register and monitor patients through the CMS registry.
Additionally, there’s still no cure for Alzheimer’s disease, and it has become one of the top 10 leading causes of death in the United States, according to the Centers for Disease Control and Prevention. The Alzheimer’s Association predicts that by 2050, 12.7 million Americans over the age of 65 may be living with the disease. Petersen highlights the importance of focusing further research on prevention, while taking advantage of current treatments.
“I always say that I think these drugs are a major step forward, but they’re not the answer. They don’t stop the disease. They don’t cure anybody, and they don’t make anybody better. But nevertheless, if you can slow down the rate at which somebody gets worse, that’s pretty important.”
Additionally, lecanemab may have untapped potential in preventing Alzheimer’s disease before people experience symptoms of cognitive decline. While it is currently being used to treat people with symptoms of Alzheimer’s, it could be used in the future to treat people before symptoms even develop.
Trials are currently underway, to determine whether in fact drugs like lecanemab might be safe and effective at preventing Alzheimer’s disease from ever appearing.
Other Treatments for Alzheimer’s
Prior to the development of the amyloid plaque-targeting drugs, the available treatments focused on addressing symptoms. These medications fall into two major categories.
Cholinesterase inhibitors
Cholinesterase inhibitors are used in all stages of AD. These include donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne). These medications are prescribed to treat symptoms related to memory, thinking, language, judgment and other cognitive processes.
“These medications are recommended for mild to moderate stages of Alzheimer’s disease for symptomatic treatment of cognition and global functioning. Donepezil also showed cognitive benefits in moderate to severe AD,” Koroma-Nelson says.
NMDA antagonists
N-methyl-D-aspartate (NMDA) antagonists are a class of drugs that include memantine (Namenda XR), which is currently used to treat Alzheimer’s. It’s used in moderate to severe stages of Alzheimer’s to improve memory, attention, reason, language and the ability to perform simple tasks. It can be used alone or with other treatments. Memantine has been shown to provide modest benefits in patients with moderate to severe Alzheimer’s by blocking the NMDA receptor to protect the brain from further damage and restore brain proteins.
These treatments can “help stabilize the clinical symptoms by slowing down the clinical progression and allowing individuals to maintain their current level of functioning for several years,” says Dr. Rawan Tarawneh, associate professor of neurology and director of both the Memory and Aging Clinic and the Cognitive Neurology section at the University of New Mexico.
While this is great, the problem is — even with that slowing of the progression — the disease will continue to get worse and patients will decline.
In addition to those treatments, there are non-pharmacological and pharmacological treatment options that can help manage symptoms, improve quality of life and maximize functional status, Koroma-Nelson says.
Among the medications and non-drug treatments that may be used in Alzheimer’s patients are:
— Anxiolytics, also known as antianxiety medications.
— Mood stabilizers.
— Sleep aids.
— Appetite stimulants.
— Vitamin E supplements.
Koroma-Nelson adds that non-pharmacological interventions that have been shown helpful include:
— Leisure activities.
— Mental stimulation programs.
— Training in coping strategies.
— Structured exercise programs.
[READ: Eating for Your Brain as a Senior.]
The Future of Alzheimer’s Treatment
Lecanemab isn’t the only drug that could change the treatment of Alzheimer’s disease in the future. Several companies are working hard to create even better treatments that go to the root of the problem and reverse the disease process itself.
“As of early 2020, there were over 120 investigational Alzheimer’s disease treatments in different stages of clinical trials,” Tarawneh notes.
One medication, called ALZ-801, is being developed by biotech firm Alzheon to target a specific gene that can inhibit amyloid plaque formation. It is one of several disease-modifying medications that target amyloid proteins that accumulate in the brain and cause a disruption of cognitive function and death of brain cells.
But some researchers have turned their attention to tau, a protein that has been shown to be involved in the development of Alzheimer’s.
Tau appears to be “more closely related to cognitive function and brain atrophy,” Tarawneh says, so targeting that protein offers a potentially very promising alternative treatment pathway to amyloid-targeting treatments.
Eli Lilly developed donanemab, or N3pG, which targets both amyloid beta and the tau protein and has also shown promising results in published clinical trial data. The company announced in July 2023 that they’ve applied for full FDA approval of the drug, and that they anticipate a decision on the potential approval of this drug in the first quarter of 2024.
These and other developmental disease-modifying medications target disease pathology and are an exciting frontier in the treatment of Alzheimer’s, Tarawneh says.
Preventative Alzheimer’s Treatment
In addition to targeting tau, researchers are looking to medications that address other changes that occur in the Alzheimer’s brain in an attempt to alter the course of the disease. Treatments that slow or reverse inflammation, immune dysfunction and damage to the blood vessels in the brain are also being investigated. These have all been implicated in some way in the inexorable advance of Alzheimer’s disease.
Tarawneh notes that in trying to find the answer to what will work best, there’s been an effort to get patients enrolled in clinical trials before they start showing symptoms of Alzheimer’s.
“This is because by the time patients with Alzheimer’s have even mild memory loss, they have already sustained significant neuronal loss, and it may already be too late to intervene, as these changes are irreversible once they happen,” Tarawneh explains.
The idea is to get a head start on the disease before patients become symptomatic, which is exactly what Peterson and the Mayo Clinic Study of Aging are working on. They’ve been running a study within the Rochester, Minnesota, community for the past 18 years. Participants are gathered via a random sample, which gives the study an impressive cross-sectional representation of the community. Every year, 3,000 participants are seen for an evaluation that includes neurological and cognitive testing, blood samples, DNA samples and imaging. As people drop out of the study or pass away, they’re replaced to keep the study around 3,000 people.
“With that kind of backdrop,” Petersen says, “we’re able to look at the performance of Alzheimer’s disease biomarkers in the general population.” The idea is that researchers can gain a much better understanding of the disease progression when they’re able to look at so many people across a longer span of time.
If you do start to notice symptoms, Scharre urges you to speak with your doctor as soon as you can. “If you notice a change in your memory or thinking, get in to see your provider as these treatments work the best if started very early in the course of the disease.”
And you should keep up with lifestyle interventions that are known to benefit the brain and body. Namely:
— Engaging in brain stimulating activities including social activities.
“Lifestyle modifications, especially among individuals with cardiovascular disease or risks, has been shown to slow cognitive decline,” Koroma-Nelson says.
Personalized Treatment as a “Cure”
As science continues to unravel the mysteries of how Alzheimer’s develops and progresses, researchers are working to create better treatments for it.
“The future of Alzheimer’s therapeutics lies in personalized medicine approaches,” Tarawneh says, adding that a blood test or another kind of biological analysis may reveal specific details about an individual’s disease pattern which could allow doctors to prescribe super-targeted treatments that look different for that person than for someone else with Alzheimer’s.
Much like how cancer treatment is becoming increasingly personalized and tailored to the biology of the individual’s specific disease state, so too will Alzheimer’s treatment become highly specific to each individual patient.
While there’s reason to hope, there’s a lot more work to be done before Alzheimer’s disease can be cured — though Scharre says he believes that a cure is possible.
“I believe we’re on our way to at least stave off or postpone the dementia symptoms of this disorder. It’ll likely take the combination of several medications that target different aspects of the disease, such as amyloid protein, tau protein, chronic inflammation and blood-brain barrier issues among others,” Scharre says.
But there’s plenty of reason to hope. In the meantime, clinical studies are key to discovering and developing new and effective therapies. You can access information about current trials and enroll yourself or a loved one via their TrialMatch site.
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New Treatments for Alzheimer’s Disease originally appeared on usnews.com
Update 02/02/24: This story was previously published at an earlier date and has been updated with new information.
Correction 02/05/24: A previous version of this article misstated the approval timeline for donanemab.
