Anti-amyloid drugs
Lecanemab and donanemab are antibodies against amyloid, the protein that builds up in the Alzheimer's brain, and in large trials they slowed early Alzheimer's disease. The slowing is real but small, they are a treatment for people who already have symptoms rather than prevention, and they cause brain swelling on scans in a substantial minority of patients.
These drugs are a decision for someone with mild cognitive impairment due to Alzheimer's, or early Alzheimer's, and their specialist, not a prevention option for healthy adults. If one is on the table, expect an APOE gene test first, and weigh a small slowing against the risk of brain swelling and the burden of infusions and scans.
What they are
Both drugs are antibodies given by infusion, and both are used in early symptomatic Alzheimer's disease. They have not been shown to prevent dementia in healthy adults.
A real but small slowing
In the lecanemab trial, the score on an 18-point clinical dementia rating scale worsened by 1.66 points over 18 months in the placebo group. Lecanemab reduced that decline by 0.45 points, about 27% slower.[1] Donanemab produced a similar 0.7-point difference on the same scale over 76 weeks.[2]
The slowing is real, but small in absolute terms. A 2026 Cochrane review, pooling 17 trials of seven such antibodies in more than 20,000 people with mild cognitive impairment or mild dementia, judged the effect on thinking and dementia severity trivial.[3]
The gap between what these antibodies do to the brain and what they do for patients is the striking part. Pooled across phase 3 trials of the whole class, including older antibodies that failed, they strip amyloid out of the brain with a very large effect, a shift of more than one full standard deviation on the standard yardstick for comparing effects measured on different scales. The effect on the dementia rating scale was a shift of 0.06 standard deviations, far below the threshold at which a patient or clinician would notice anything; even donanemab, the best performer, moved the scale by about 0.70 points against the 1-point bar for a noticeable difference.[4] The case for treating longer is contested. The manufacturer's three-year donanemab follow-up reports a difference of about 1.2 points on the dementia scale, but measured against an outside comparison group drawn from a separate observational study, because the original placebo group had been switched onto the drug.[5] Other researchers replied that the data "do not robustly support" a changed course of disease.[6]
Brain swelling and bleeds
Both drugs cause amyloid-related brain swelling (ARIA-E, short for amyloid-related imaging abnormalities with oedema) on MRI scans:
- About 13% of patients on lecanemab and 24% on donanemab at its original dosing, mostly without symptoms.[7][8]
- Small brain bleeds are counted separately, on top of those figures.
- Pooled across 11 trials (about 13,600 people), about 107 more people per 1,000 treated showed swelling on scans than on placebo; swelling that caused symptoms was rarer, about 29 more per 1,000, which the review rated as probably little or no difference, based on only 2 trials.[9]
- A slower donanemab dose build-up, adopted in the US label in 2025, lowered swelling to about 16%.[10]
Who is at highest risk
People with two copies of the APOE ε4 gene variant are at highest risk of these side effects. The European licences for both drugs, and the UK licence for lecanemab, exclude them, so a gene test is part of eligibility there. US labels advise testing but do not require it. The details are on APOE4 testing.
The burden of treatment
Treatment means regular infusions and repeated MRI scans to watch for swelling. That cost in time and monitoring sits alongside the modest benefit.
What to do
- Don't think of these drugs as prevention. For lowering dementia risk, the levers are on Dementia prevention.
- If you or a relative has early symptoms and a specialist raises one of these drugs, ask about the expected size of the benefit, your APOE genotype, and how swelling will be monitored.
Further reading
- van Dyck CH et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med 2023.[11]
- Sims JR et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA 2023.[12]
- Avgerinos KI, et al. Critical assessment of anti-amyloid-β monoclonal antibodies effects in Alzheimer's disease: a systematic review and meta-analysis highlighting target engagement and clinical meaningfulness. Sci Rep 2024.[13]
- Zimmer JA, et al. Donanemab in early symptomatic Alzheimer's disease: results from the TRAILBLAZER-ALZ 2 long-term extension. J Prev Alzheimers Dis 2026 — company-run extension.[14]
- Nonino F et al. Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease. Cochrane Database Syst Rev 2026.[15]
- Wang H et al. The effect of modified donanemab titration on amyloid-related imaging abnormalities with edema/effusions and amyloid reduction: 18-month results from TRAILBLAZER-ALZ 6. J Prev Alzheimers Dis 2025.[16]