Anti-amyloid drugs may not work against Alzheimer's but if so, what will?

Are anti-amyloid drugs as effective against Alzheimer’s disease as experts had hoped? Image credit: smodj/Getty Images This article originally appeared on Medical News Today More than 55 million people worldwide are living with Alzheimer’s disease, estimates suggest.

Treatment for Alzheimer’s disease currently includes medications, such as anti-amyloid drugs that work to remove amyloid-beta plaques from the brain of those with early Alzheimer’s disease. A new study says that anti-amyloid medications may not have any clinically meaningful positive effects, and may increase the risk of swelling and bleeding in the brain.

Scientists believe there are more than 55 million people globally living with a type of dementia called Alzheimer’s disease . While researchers are still unclear as to the actual cause of the condition, the current theories include a build-up of two proteins in the brain that form beta-amyloid plaques and tau tangles .

There is currently no cure for Alzheimer’s disease. The disease is treated through a multifactorial approach that includes lifestyle changes , therapies , and medications that may help slow progression of the condition and manage its symptoms.

Some of these medications include anti-amyloid drugs , which work to remove amyloid-beta plaques from the brain of those with early Alzheimer’s disease. Now, a paper recently published in the Cochrane Database of Systematic Reviews has concluded that anti-amyloid medications may not have any clinically meaningful positive effects, and may actually increase the risk of swelling and bleeding in the brain.

Anti-amyloid meds may make little to no difference to dementia symptom severity For this review, researchers analyzed data from 17 clinical trials, encompassing a total of more than 20,000 study participants with average ages between 70 and 74. All the studies used were researching the use of anti-amyloid medications to treat participants with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease.

At the study’s conclusion, the researchers found that, after 18 months, anti-amyloid medications may make little to no difference to dementia symptom severity and probably make little to no difference in the decline of memory or thinking ability. “Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients,” Francesco Nonino , MD, a neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna, Italy, and lead author of this study said in a press release .

According to Nonino, “there is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect.“ “While early trials showed results that were statistically significant, it is important to distinguish between this and clinical relevance. It is common for trials to find statistically significant results that do not translate into a meaningful clinical difference for patients,” he pointed out.

Additionally, researchers reported that the use of anti-amyloid medications likely increased the risk of swelling and bleeding in the brain. Does this mean anti-amyloid drugs are better left behind?

Medical News Today had the opportunity to speak with Megan Glenn , PsyD, a clinical neuropsychologist at the Center for Memory and Healthy Aging at the Hackensack Meridian Neuroscience Institute at Jersey Shore University Medical Center in New Jersey, about this review. Glenn, who was not involved in the research, commented that while this review provides a valuable, high-level summary of the evidence to date, we must nevertheless be very careful in how we interpret its conclusions.

“It’s crucial to understand that this review pools data from 17 different trials spanning many years, the majority of which involved older, unsuccessful drugs,” Glenn explained. “Only two of the trials studied the recently approved treatments, lecanemab and donanemab .

While the review’s overall conclusion finds no average clinically meaningful effect across all these drugs, it doesn’t erase the specific findings from the pivotal trials for the newer medications,” she emphasized. “Those individual trials for lecanemab and donanemab did show a small, statistically significant slowing of cognitive and functional decline.

This review reinforces the central question we as clinicians have been grappling with all along: Is that small effect — for instance, a 1-to-2-point change on a 90-point cognitive scale — truly meaningful in a patient’s daily life? When you weigh this modest benefit against the very real and frequent risks of brain swelling and bleeding, the risk-benefit calculation remains a serious conversation that every patient and family must have with their doctor.” – Megan Glenn, PsyD Understanding the importance of continued research Peter Gliebus , MD, chief of neurology and director of cognitive and behavioral neurology at Marcus Neuroscience Institute, a part of Baptist Health, told MNT that when it comes to Alzheimer’s disease research, it is crucial for scientists to assess both successful and unsuccessful medications.

“When a drug or drug class shows no clinical benefit, it prompts a reassessment of the disease mechanisms, drug properties, and fundamental hypotheses,” Gliebus, who was not involved in the current review, explained. “Understanding why some drugs fail can offer valuable insights into drug delivery, blood-brain barrier crossing, dosing strategies, patient selection, and trial design,” he continued.

While Gliebus reiterated that “the review emphasizes that removing amyloid from the brain doesn’t always lead to clinical improvement,” he also outlined why it is important to stay hopeful, noting that: “Learning from failures is vital for scientific advancement, helping to refine research questions, prevent repeated mistakes, and develop more effective, targeted treatments. By considering both successful and unsuccessful approaches, the field stays dynamic, self-corrects, and remains receptive to new ideas.” Review results do not change real-life clinical practice MNT also spoke with Paul Monroe Butler , MD, PhD, an assistant professor in neurology at Harvard Medical School and neurologist at Mass General Brigham, about the recent review.

Butler, who was likewise not involved in this research, said his first reaction was that this review does not change what occurs in real clinical practice with the FDA-approved therapies lecanemab and donanemab. “The study pools successful and unsuccessful anti-amyloid drugs together, so it is not surprising that the average class effect looks modest,” he pointed out.

However, he added: “I wouldn’t accept the premise that anti-amyloid therapy has no clinical viability. At Mass General Brigham, one of the largest treatment programs in the world, we are seeing that these therapies can be delivered safely and can meaningfully slow progression for many patients with early-stage Alzheimer’s disease.“ “The real future is building on that foundation — combining amyloid-lowering with next-generation treatments that target tau, inflammation, and neurodegeneration,” Butler stressed.

He also noted that: “Alzheimer’s is not a single-pathway disease, and no one mechanism will be the whole answer. Each study — whether it succeeds or fails — sharpens our understanding of the biology, helps us identify which patients benefit, and guides us toward more effective and precise treatments.

That iterative process is exactly how we move from early, modest therapies to increasingly transformative ones.” What other treatment options might work for Alzheimer’s disease? If the anti-amyloid medication approach has no clinical viability, then what other treatment options are there that might work?

Glenn said the focus on amyloid has been important, but we know Alzheimer’s is a complex disease. “In practice, we often see a mix of issues in the brain beyond just amyloid plaques,” she explained.

“This is why the future of treatment must look at other targets.” Glenn said several promising strategies are being pursued, including: Targeting tau: “Another protein called tau forms toxic tangles inside brain cells, and the amount of tangles is closely linked to memory loss. Researchers are developing therapies to stop these tangles from forming and spreading.” Improving overall brain health which includes reducing chronic inflammation and supporting the brain’s energy supply: “This is the ‘ heart-brain connection ’ you hear about — the idea that managing blood pressure and diabetes , along with lifestyle choices like a heart-healthy diet and exercise, can help protect the brain,” she added.

“The future [of Alzheimer’s treatment] likely isn’t one single magic bullet,” Glenn said. “The most effective approach will probably be a combination therapy, where treatments are personalized to address the specific mix of issues — whether it’s amyloid, tau, or vascular problems — in an individual patient.”