Survey: Neurologists split on prescribing new Alzheimer’s treatments

As more than 7,500 clinicians and researchers converge in Philadelphia for the Alzheimer’s Association International Conference, a sharp division is emerging over new treatments for the disease that brings them together each year. This divide is over when to prescribe one of the newer drugs to treat Alzheimer’s disease. Lecanemab (Leqembi) was approved by the Food and Drug Administration in 2023 but received a negative recommendation by European Medicines Agency’s human medicine products committee last week. Donanemab (Kisunla) was approved by the FDA in July.

Both have critical health and financial implications that will affect the treatment of Alzheimer’s, but may also affect the diagnosis patients receive — depending on their neurologist’s stance.

At the heart of the divide is a pernicious protein in the brain called beta-amyloid. In Alzheimer’s disease, deposits of this protein, called plaques, disrupt brain function, affecting memory and cognition.

We are doctors who specialize in Alzheimer’s research and treatment. To gain a better understanding of how our field views the new treatment landscape that’s made headlines and headways, as well as stirred serious debate in just the past two years, we surveyed neurologists from the U.S. and Europe on June 14, 2024, using an online platform in collaboration with Sermo, a physician social network. The survey was closed after eight hours, by which time 268 neurologists had responded. The main limitations of the survey include sampling bias, unmeasured confounding variables, and other factors.

The results reveal deep divides: 59% of U.S. neurologists endorse amyloid-targeted therapies (such as the two that have been approved), but 41% remain skeptical due to previous failures and side effects. And only 5% of neurologists view biomarker changes (such as imaging or blood tests that measure amyloid plaque reduction) as a measure of clinical benefit.

More than 47 million Americans have a silent build-up of amyloid, meaning they have high levels of amyloid plaques without any memory loss or cognitive impairments. Neurologists refer to this as preclinical Alzheimer’s disease.

With the advent of amyloid plaque-clearing monoclonal antibodies like donanemab and lecanemab, and others in the pipeline, Alzheimer’s therapeutics are projected to grow to be a $30 billion industry in the next decade, and potentially usher in an entirely new way to think about and treat dementia.

Yet our survey of neurologists reveals significant divisions within the medical community. These rifts are influenced by geographic location, differing theories of Alzheimer’s pathology, and concerns over serious adverse effects like brain hemorrhaging associated with these new drugs.

No matter where people live, they have a coin-flip chance of finding a neurologist willing to prescribe an amyloid-targeting treatment for preclinical Alzheimer’s — which would be an off-label use, meaning a use other than what the FDA approved it for.

Our survey showed that just over half of neurologists in the U.S. and Europe are ready to diagnose Alzheimer’s based on blood biomarkers even before symptoms appear and prescribe new drugs like Leqembi or Kisunla without any need for FDA approval for this use. The other half remain skeptical, likely due to past failures of amyloid-targeting drugs in clinical trials or a reluctance to replace clinical assessments with biomarkers.

This division highlights the urgent need for solid evidence showing the reliability of beta-amyloid biomarkers in Alzheimer’s diagnosis and treatment.

Location changes how likely someone would find a doctor willing to prescribe anti-amyloid treatment. Even though these anti-amyloid drugs are not being marketed in Europe, 83% of European neurologists embrace the new treatments as standard care, whereas only 59% of their U.S. counterparts agree, reflecting stark regional contrasts in perception and likely, practice.

Nearly half of U.S. neurologists remain skeptical partly because they want to see more robust evidence of the drugs’ effectiveness. Notably 95% of neurologists overall did not view biomarker changes as a measure of clinical benefit — they valued cognitive and functional benefits as well as reduction of the volume of the hippocampus (a memory center in the brain) over plaque reduction. This skepticism is reflected in the slow adoption rate of anti-amyloid therapies in the U.S. Of the several million Americans with early Alzheimer’s who are potentially eligible for this therapy, we estimate from registries that only about 10,000 have been prescribed Leqembi since its approval by the FDA in July 2023 and the start of Medicare coverage.

In our survey, a significant concern among 71% of neurologists was the potential for severe adverse effects such as brain swelling and microbleeds (termed amyloid-related imaging abnormality or ARIA), which further complicates the decision to prescribe these new treatments. Notably, 8% of U.S. neurologists felt the risks were so dangerous that they would never use these treatments. Another 28% were also seriously concerned about the greater loss of brain volume associated with amyloid-targeted antibodies.

This professional divide directly influences patient care, where the choice of treatment can differ significantly based on a physician’s stance on new therapies.

Anyone who knows one of the 45 million people worldwide living with Alzheimer’s disease would likely do anything to help stabilize their symptoms or slow their cognitive decline due to the progression of the illness. This ongoing debate over treatment underscores the need for conclusive research validating biomarker findings and potentially a push toward harmonizing treatment approaches to ensure consistent and effective patient care.

To improve patient care and unify the field of neurology, informed decisions must be based on comprehensive data. We urge companies developing and marketing anti-amyloid therapies to fully disclose their clinical trial databases so physicians and researchers can better understand the potential risks and benefits of these drugs.

There’s limited proof, for example, that reducing amyloid plaques directly correlates with outcomes. Yet treatment guidelines for donanemab suggest stopping therapy once plaque levels normalize. Open access to these datasets would enable dementia specialists to confirm the validity of this biomarker-based treatment endpoint.

While pharmaceutical companies and researchers funded by the National Institutes of Health may be reluctant to share their data due to fears of misuse, the benefits of transparency outweigh these concerns. The prevailing mistrust in commercial motives, fueled by a divisive political climate, could be mitigated by greater openness. Although 60% of Americans believe prescription drugs have made their lives better, more than 80% believe that pharmaceutical companies prioritize profits over patients, underscoring the need for transparency to improve public perception.

Narrowing the divide in Alzheimer’s treatment is crucial to avoid inconsistent practices and care, which prevent many eligible people from accessing potentially transformative medications. By making more clinical trial data available, pharmaceutical companies can help restore public trust and enable health care providers to overcome the knowledge gaps that cause disparities in treatment recommendations.

The European Medicines Agency declined to approve Leqembi because the small clinical effects seen with the drug were “not large enough to outweigh the risks” of brain swelling and bleeds being serious enough in some patients to require hospitalization.

We — and many of our colleagues — will wait to see if the marked enthusiasm of the European neurologists, as expressed in this survey, is enough to reverse the European Medicines Agency’s stance, or if more outcomes and safety data, as we are calling for, will be needed.

Murali Doraiswamy, M.B.B.S., is professor of psychiatry and geriatrics at Duke University School of Medicine and a member of the Duke Institute for Brain Sciences. Lon S. Schneider, M.D., is professor of psychiatry, neurology, and gerontology at the University of Southern California and holds the Della Martin Chair in Psychiatry and Neuroscience at USC. The authors thank Sermo for powering the international survey of neurologists. Both authors have served as advisors to government agencies, pharmaceutical companies, and advocacy groups in this field, but this survey was not funded by any company.