Do Alzheimer's Drugs Actually Work? What a Major New Review Found

If your family is navigating an Alzheimer's diagnosis, you've almost certainly heard about the newer anti-amyloid drugs — lecanemab, sold as Leqembi, and donanemab, sold as Kisunla. They've been called breakthroughs. They cost tens of thousands of dollars a year and require regular intravenous infusions and repeated brain scans. And a major new evidence review just put them to the most rigorous test they've faced. The headlines have simplified this into a binary — "Alzheimer's drugs don't work" — but the reality is far more nuanced, and families deserve a fuller picture.

I've reviewed the Cochrane analysis and the response from the research community. Here's what families need to know.

Why Amyloid Matters in Alzheimer's

To understand what these drugs are trying to do — and why this review is so significant — it helps to understand the role of amyloid in Alzheimer's disease.

For more than 30 years, the dominant theory in Alzheimer's research has been the amyloid hypothesis. In a healthy brain, a protein called amyloid-beta is produced and cleared naturally. In Alzheimer's disease, that clearance process fails. Amyloid-beta accumulates and forms sticky plaques between neurons. These plaques are believed to trigger a cascade of damage: they provoke inflammation, disrupt communication between neurons, and are associated with the accumulation of another toxic protein called tau, which forms tangles inside neurons and leads to cell death.

The logic behind anti-amyloid drugs is straightforward: if amyloid plaques drive the disease, then removing them should slow or stop it. That hypothesis has guided billions of dollars in research investment and led directly to the development of the drugs being evaluated in this review.

What the Cochrane analysis now forces us to ask is whether that logic holds — whether removing amyloid, even successfully, is enough to change the clinical course of the disease.

What the Cochrane Review Found

The Cochrane Collaboration — widely regarded as the gold standard for evaluating medical evidence — published a meta-analysis in April 2026 examining 17 clinical trials involving 20,342 participants. The trials tested seven different anti-amyloid monoclonal antibodies in people with mild cognitive impairment or mild dementia due to Alzheimer's disease.

The full review, led by neurologist and epidemiologist Francesco Nonino at the IRCCS Institute of Neurological Sciences of Bologna, reached a stark conclusion: the absolute effects of anti-amyloid drugs on cognitive decline and dementia severity were "absent or trivial," falling well below established thresholds for what is considered a minimum clinically important difference.

The drugs do successfully clear amyloid protein from the brain. That part works. But the review found that removing amyloid plaques does not reliably translate into meaningful clinical improvement. As Nonino stated: "Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients. There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect."

The Risks

Anti-amyloid drugs increase the likelihood of amyloid-related imaging abnormalities, or ARIA — a term that encompasses both brain swelling (ARIA-E) and brain bleeding (ARIA-H). While ARIA was detected on routine MRI in 21% of lecanemab-treated patients and 37% of donanemab-treated patients, the majority of these cases were asymptomatic. Symptomatic ARIA — headaches, confusion, dizziness — occurred in approximately 3% of patients on lecanemab and about 6% of those on donanemab. Symptomatic brain hemorrhage specifically occurred in less than 1% of patients, and serious symptomatic ARIA in 0.7%. However, in rare cases ARIA can be fatal: three deaths were attributed to ARIA in the donanemab trial. The risk is significantly higher in carriers of the APOE4 gene variant. The FDA requires a boxed warning — the highest level of safety precaution — on these drugs because of the ARIA risk.

Patients receiving these drugs require regular brain imaging to monitor for ARIA, which adds to both the cost and the burden of treatment. The long-term consequences of repeated episodes of brain swelling and microbleeding remain unclear.

Why Many Experts Disagree

The Cochrane review drew immediate and forceful pushback from many Alzheimer's researchers, and their criticisms deserve serious consideration.

The central issue is methodological. Of the seven drugs analyzed, five — bapineuzumab, crenezumab, gantenerumab, solanezumab, and aducanumab — either failed their clinical trials or were withdrawn from the market. Only lecanemab (Leqembi) and donanemab (Kisunla) showed positive results in large Phase III trials and remain FDA-approved.

By pooling all seven drugs together — including five that are widely acknowledged as failures — the overall effect size is mathematically diluted. The UK Dementia Research Institute responded directly to this concern: "Once failed and successful programmes are combined into a single pooled estimate, the average will inevitably look weaker than the best performing agents. That is not a biological insight, it is simply the arithmetic consequence of mixing negative and positive studies together."

Eisai, the manufacturer of Leqembi, called the review "scientifically deeply flawed by inappropriately combining ineffective antibodies and failed studies with effective, regulatory approved anti-amyloid treatments."

Alzheimer's Research UK also noted the review had "major limitations" given that much of the evidence came from older experimental drugs that were discontinued.

What the Individual Drug Data Shows

When you look at lecanemab and donanemab on their own merits — separate from the pooled Cochrane analysis — the picture is different, though still subject to interpretation.

Lecanemab was tested in the CLARITY AD trial and received full FDA approval in July 2023. It slowed cognitive decline by approximately 27% over 18 months compared to placebo, as measured by the CDR-SB scale. Four-year open-label extension data showed continued slowing of decline, with 69% of patients in the low-tau subgroup maintaining or improving cognitive function.

Donanemab was tested in the TRAILBLAZER-ALZ 2 trial and received FDA approval in July 2024. It slowed cognitive decline by approximately 35% over 18 months in patients with low-to-medium levels of tau protein — those in the earlier stages of disease — and by about 29% in the overall combined trial population.

Both drugs received support from the FDA's advisory committees — lecanemab was voted on favorably by a unanimous 6-0.

The question that divides the field is whether slowing decline by 27-35% over 18 months is clinically meaningful for individual patients and families. Some neurologists and patient advocates argue that any slowing of an otherwise relentless disease is valuable. Others counter that the measured differences on cognitive scales are too small for patients or families to notice in daily life — and that the risks of ARIA and the cost of treatment may not be justified by such modest effects.

What This Means for Families

This is not a simple good-drug or bad-drug story. It is a story about how we interpret evidence and make medical decisions when the data is genuinely uncertain.

Have an honest conversation with the neurologist. If your parent has been diagnosed with early Alzheimer's and is considering lecanemab or donanemab, the most important step is a detailed, individualized discussion. Ask: what is the expected clinical benefit for my parent specifically? What are the risks of ARIA given their cardiovascular profile? How will we monitor for side effects? And what does the evidence actually support in this specific case?

Understand what the drugs can and cannot do. These drugs do not reverse cognitive decline. They do not restore lost function. At best, the evidence suggests they may modestly slow the rate of decline in some patients with early-stage disease. That may be meaningful for some families. For others, the risks and costs may not be justified.

Know that other options are being pursued. The Cochrane review's senior author, Edo Richard, Professor of Neurology at Radboud University Medical Centre, put it this way: "I see Alzheimer's patients in my clinic every week and I wish I had an effective treatment to offer them. Existing approved drugs offer some benefit for some patients, but there remains a high unmet need for more effective treatments. Sadly, anti-amyloid drugs do not offer this and bring additional risks. Given the absence of correlation between amyloid removal and clinical benefit, we need to explore other pathways."

The Alzheimer's research community is increasingly looking beyond amyloid — toward tau pathology, neuroinflammation, immune mechanisms, and metabolic approaches. Multiple clinical trials targeting these alternative pathways are currently underway. That may be where the next generation of genuinely effective treatment lies.

The Bottom Line

The Cochrane review does not prove that lecanemab and donanemab don't work. Rather, it shows how nuanced the conversation about these therapies needs to be — how much they help, at what cost, and at what risk. For families facing one of the most difficult diagnoses in medicine, the answer to "should we try this drug?" is not a blanket yes or no. It is a careful, individualized decision made with a neurologist who can weigh the evidence against your parent's specific clinical picture.

The science of Alzheimer's treatment is moving — but it has so far failed to deliver truly game-changing therapies. And families deserve to know that.

Disclaimer The information provided in this article is intended for general counseling purposes only and does not constitute medical care or the practice of medicine. No physician-patient relationship is established. Counseling is intended for informational and educational purposes only and should not be relied upon as a substitute for professional medical advice, diagnosis, or treatment. Any specific medical concerns should be addressed directly with a primary healthcare provider or another qualified medical professional.

Dr. Ryan Van Wert is a Stanford-trained, triple board-certified physician and founder of Kin Concierge, a bespoke services firm that helps seniors and families navigate the complexities of aging with a suite of advisory, healthcare coordination and supportive services.