New treatments for Alzheimer’s offer hope for people living with dementia—but these new drugs are not without side effects. Learn what a neurologist has to say about what these new medications mean for the future of Alzheimer’s treatment.
Brain diseases like Alzheimer’s and other dementias have a devastating impact on individuals and their families. Recent research has led to advancements in diagnosing and screening for Alzheimer’s disease as well as a new class of drug treatment options that offer hope of halting disease progression. But how safe and effective are these therapies, and who can use them?
We hosted a webinar to explore recent advancements in the diagnosis and treatment of dementia and address questions around this new class of drugs. Ronald C. Petersen, MD, PhD, director of the Mayo Clinic Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging, discussed the current state of Alzheimer’s research, advancements that may lead to earlier detection and treatment, and what this means for people with dementia.
Changing Terminology Around Dementia
Much like our understanding of neurodegenerative brain diseases, the terminology used to discuss dementia has shifted over the years to become more accurate and fully encompass the many different ways symptoms may appear.
“When I started in the field decades ago, someone would come in with a memory complaint and we’d classify them as either cognitively normal or possibly having dementia,” Dr. Petersen says. “But over time, we came to appreciate that this is a broader continuum… There are no hard [boundaries] between these various conditions [that may cause cognitive decline].”
Dr. Petersen and his peers realized there is an observable stage of cognitive decline that occurs between normal aging and the onset of dementia—a condition they now call mild cognitive impairment (MCI). People with MCI have memory issues beyond those associated with normal aging but can still keep up with daily functions. Recognizing and diagnosing this condition is vital because it enables people to get earlier and potentially more effective treatments to delay the onset of dementia.
Blood Tests for Alzheimer’s Disease
The last few years have seen remarkable progress in Alzheimer’s research, including efforts to develop blood tests to detect the disease. These blood tests are designed to measure a biomarker (a biological indicator) that shows when the underlying causes and mechanisms of a disease are present. The goal is to accurately detect the misfolded amyloid-beta and tau proteins that cause Alzheimer’s and measure the amount of these harmful proteins in a person’s blood at any given time.
“Blood tests have been developed and have been refined to really characterize a person’s amyloid level based on their blood test,” says Dr. Petersen. “These need further refinement, but that’s one direction in which the field is moving.”
These blood tests are significant for several reasons. First, they can identify when someone is in the early stages of Alzheimer’s disease, enabling earlier treatment and interventions to slow the progression of the disease. Secondly, this type of testing will allow researchers to measure the effectiveness of different drug treatments by identifying whether they lower the amount of amyloid-beta and tau in the brain. Thirdly, they will give researchers easier, quicker access to data from underrepresented groups of people with dementia.
“One of the legitimate criticisms of clinical research [and drug trials] in Alzheimer’s disease and dementia is that they have largely involved higher educated, higher socioeconomic class, often white individuals,” says Dr. Petersen. “Blood tests will now give us access to the biologic characteristics [and] the diagnostic features of individuals from underrepresented groups.”
New Alzheimer’s Drug Treatment Options
Thanks to new research, there is more hope than ever before for effectively treating Alzheimer’s disease. Dr. Petersen explains that there are currently two types of drugs for Alzheimer’s disease: symptomatic and disease-modifying.
“The symptomatic drugs have been around for literally decades now,” he says. “They’re helpful at perhaps alleviating some of the symptoms of Alzheimer’s disease for a period of time, but they’re not getting at the disease process [to slow or stop progression].”
Disease-modifying therapies target the underlying causes of Alzheimer’s to slow the progression of the disease. “What’s been exciting in the last few years has been the development of disease-modifying therapies,” says Dr. Petersen. “There have been three drugs now that have demonstrated positive results in clinical trials.”
Those drugs are aducanumab, lecanemab, and donanemab, and all three focus on removing or preventing amyloid-beta protein buildup in the brain.
As the first new Alzheimer’s disease treatment since 2003, aducanumab was the first in this new class of drugs to target the harmful buildup of amyloid protein in the brain. Aducanumab made waves when the FDA granted it accelerated approval in 2021—but while some people were thrilled about its approval, others expressed concerns. Some medical experts felt the results of clinical trials were unclear and that the possible complications of using the drug outweighed its benefits. The maker, Biogen, is currently conducting a post-approval trial to confirm clinical benefits.
Lecanemab was granted accelerated approval in January 2023. Its makers, Eisai and Biogen, conducted a study that showed promising results. “In this study, they demonstrated that lecanemab did in fact slow progression of the disease by about 27% at 18 months,” says Dr. Petersen.
“When you look at the biological impact of the drug on the disease, [it] shows remarkable lowering of the amyloid level in the brain. So it does what it is supposed to do, and in fact, it appears to have a clinical impact.” The FDA granted full approval to Lecanemab in early July 2023.
Donanemab was also granted accelerated approval in January and is currently undergoing additional clinical trials by its maker Eli Lilly. In donanemab’s early trials, the drug slowed the progression of Alzheimer’s disease by 35%.
“Importantly, 72% of the participants in the study had their amyloid levels reduced to negative by 18 months,” says Dr. Petersen. “Now we’re getting a trend that the more amyloid you remove from the brain, the more likely you are to see clinical stabilization or a lessening of the rate of progression.”
Donanemab is still awaiting full FDA approval.
Drawbacks to Alzheimer’s Disease Drugs
One of the major controversies around these new Alzheimer’s treatments is whether the benefits outweigh the risks of possible side effects.
“The bad news is, there are side effects of these drugs,” says Dr. Petersen. “These drugs that lower amyloid levels have the risk of producing some swelling in the brain (edema) or possibly bleeding in the brain (hemorrhage).”
Eisai’s lecanemab trial revealed there was a 12.5% rate of edema versus the placebo rate of 1.7% and a hemorrhage rate of 17% versus the 8.7% placebo rate. Donanemab showed even higher risks: a 24% edema rate compared to 6.1% for the placebo group, and a 31.4% hemorrhage rate compared to 13.6% for the placebo group.
“About three-quarters of the people who have these imaging abnormalities are asymptomatic,” says Dr. Petersen. “But a quarter of them did have various symptoms: headache, dizziness, confusion. So the drugs are effective, but they may not be completely [harmless].”
The price and accessibility of these drugs are another concern for many people. Lecanemab is estimated to cost about $26,500 a year. Medicare officials have said they will cover the drug now that it has received full FDA approval—however, there is a caveat. “They’re operating under what’s called a National Coverage Decision, which they put in place last year, saying that if these drugs are approved by the FDA, we’d like to learn more about them, we’d like to collect more data, and we’d like people who get these drugs covered by us to be in a registry,” says Dr. Petersen.
While Dr. Petersen thinks data collection is a good idea, he’s concerned that a registry may result in fewer people from marginalized groups accessing the drugs. “The requirement of a registry may enhance or amplify that disparity,” he says. “Physicians who treat patients from underrepresented groups may not be quite as willing to go through all the paperwork.”
A Hopeful Future for Dementia Treatment
While these new drugs don’t cure Alzheimer’s or other dementias, they can preserve a person’s cognitive function for longer, giving people more time to spend with their families and enjoy their lives. “If you can keep me where I am at now for another nine or 12 months, is that important? I think most people would say yes,” says Dr. Petersen.
Right now, the drugs are used for people with MCI and mild dementia due to Alzheimer’s disease. However, there may be potential to use them as early intervention measures to prevent symptoms while the disease is in its earliest stages.
“The real strategy would be, let’s move back up that continuum [of cognitive decline],” says Dr. Petersen. “Now that we have these imaging biomarkers and spinal fluid biomarkers, maybe blood biomarkers, shouldn’t we treat people who are cognitively normal but have the biologic features of Alzheimer’s disease?” There is currently a trial underway using lecanemab to explore this possibility.
After so long with limited options, people with Alzheimer’s disease finally have hope for treatments that can significantly improve their quality of life and allow them more time with the people they love. With further research, we will uncover even earlier and more effective treatment options not just for Alzheimer’s, but for all neurodegenerative diseases.
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