Who Qualifies for Leqembi or Kisunla, and What Does APOE4 Mean for ARIA Risk?

A new diagnosis of mild cognitive impairment or early Alzheimer’s disease usually brings three questions within days. Can I get one of the new drugs? How much would it help? And what does my APOE4 result mean for the risk of brain swelling? A positive amyloid test, whether from a PET scan, a spinal tap or a blood draw, often arrives before anyone has explained what treatment would involve. This guide covers lecanemab (Leqembi) and donanemab (Kisunla), the two anti-amyloid antibodies available in the United States in 2026.

The Short Answer

Leqembi and Kisunla are for people who already have symptoms: mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease, with amyloid confirmed by testing.^1,2 In their pivotal trials, they slowed decline on an 18-point clinical scale by 0.45 to 0.70 points over about 18 months, roughly 27% to 36% less decline than placebo.^3,4 They do not stop or reverse the disease.

The main risk is ARIA (amyloid-related imaging abnormalities): brain swelling or small bleeds seen on MRI, usually without symptoms. The risk climbs with each copy of APOE4. ARIA-E (swelling) occurred in 32.6% of APOE4 homozygotes on lecanemab and 40.6% on donanemab, against 5.4% and 15.7% of non-carriers.^5,4 Neither drug is approved for people without symptoms.

What Are Leqembi and Kisunla?

Both are monoclonal antibodies, lab-made immune proteins given to clear amyloid, the protein that forms the plaques that define Alzheimer’s disease. Lecanemab binds aggregated soluble and insoluble forms of amyloid beta, including the small soluble clumps called protofibrils.^1,3 Donanemab targets a modified form of amyloid called N-terminal pyroglutamate amyloid beta.⁶

Leqembi received traditional FDA approval in July 2023.⁷ Kisunla was approved on July 2, 2024.⁸ Both labels say treatment should start in the population the trials studied: people with MCI or mild dementia, with amyloid pathology confirmed before the first dose.^1,2

How Much Do Leqembi and Kisunla Slow Alzheimer’s Decline?

Both drugs produced a modest, statistically clear slowing of decline over about 18 months. Neither improved memory on average, and people in both treated groups continued to decline.^3,4

Lecanemab (CLARITY AD). The trial randomized 1,795 people aged 50 to 90 with early Alzheimer’s disease. The main outcome was the Clinical Dementia Rating Sum of Boxes (CDR-SB), a clinician-rated scale of memory, thinking and daily function scored from 0 to 18, where higher is worse. Over 18 months, scores worsened by 1.21 points on lecanemab and 1.66 on placebo: a difference of 0.45 points, or about 27% less decline. Amyloid on PET fell by 59.1 centiloids more than on placebo.³

Donanemab (TRAILBLAZER-ALZ 2). The trial randomized 1,736 people with early symptomatic disease, grouped by how much tau (the second Alzheimer’s protein) showed on PET. Over 76 weeks, in the low-to-medium tau group, decline on the integrated Alzheimer’s Disease Rating Scale (iADRS) was 35% slower than on placebo, and CDR-SB decline was 36% slower, a 0.67-point difference. Across all participants, the CDR-SB difference was 0.70 points. In the low-to-medium tau group, treated participants had a 38.6% lower risk of moving to the next clinical stage during the trial.⁴

What Does a 0.45-Point Difference on the CDR-SB Mean?

A 0.45-point difference is small on an 18-point scale, and it sits at the center of the debate about these drugs. Studies of what clinicians judge to be meaningful decline in one person put the threshold at about 1 to 2 CDR-SB points.⁹ The average gap between drug and placebo in both trials falls below that range.^3,4

That comparison has limits. The 1-to-2-point figure describes change within one person, while the trial number is an average difference between two groups. Supporters argue that a steady slowing could add up over years of treatment; critics answer that 18 months of placebo-controlled data cannot show that. What the trials do establish is an effect that is real, modest, and paid for with monitoring and risk.

How Do Leqembi and Kisunla Compare?

The trials used different scales, tau selection and follow-up, so the numbers cannot be compared head to head. No published trial has compared the two drugs directly on clinical outcomes.

Who Qualifies for Leqembi or Kisunla?

Eligibility rests on four checks: the stage of illness, proof of amyloid, a recent brain MRI, and APOE genotyping.

• Stage: MCI or mild dementia due to Alzheimer’s disease. The appropriate use recommendations, written by independent experts to carry the trials into everyday practice, use a Mini-Mental State Examination score of 22 to 30 for lecanemab and 20 to 30 for donanemab.^5,6 Someone already in the moderate stage is outside the studied population.
• Confirmed amyloid: both labels require it before the first dose.^1,2 The recommendations name amyloid PET or cerebrospinal fluid testing.^5,6 A 2025 Alzheimer’s Association guideline added that, in specialty memory care, a blood test with at least 90% sensitivity and 90% specificity can substitute for PET or spinal fluid testing. Many commercial blood tests do not reach that bar.¹²
• A recent MRI: the recommendations call for a brain MRI within 12 months before the first dose, read for the findings described in the next section.^5,6
• APOE genotype: both labels say APOE4 testing should be done before treatment, after a discussion of what each result would mean.^1,2

Tau PET is not required for donanemab in routine care, even though the trial used it.⁶ If the diagnosis itself is still uncertain, the first step is to understand what an MCI diagnosis means and what is causing it.

What Rules Someone Out of Anti-Amyloid Treatment?

Most exclusions point to one problem: fragile blood vessels that are more likely to bleed during treatment. Amyloid also collects in the walls of brain blood vessels, a condition called cerebral amyloid angiopathy (CAA). Its MRI signs include tiny old bleeds (microhemorrhages), iron staining along the brain surface (superficial siderosis) and prior larger bleeds, and APOE4 is associated with it. At least 2 microhemorrhages or 1 area of superficial siderosis at baseline raise the risk of ARIA.¹

The lecanemab recommendations exclude people with:⁵

• more than 4 microhemorrhages, any area of superficial siderosis, or a prior brain bleed larger than 10 mm;
• severe white matter disease (Fazekas grade 3), more than 2 lacunar infarcts, or a stroke involving a major vascular territory;
• a need for anticoagulants such as warfarin, a direct oral anticoagulant or heparin;
• a bleeding disorder that is not under control, including a platelet count below 50,000 or an INR above 1.5.

The donanemab recommendations apply the same core MRI exclusions: more than 4 microbleeds, cortical superficial siderosis, or a major vascular contribution to cognitive impairment.⁶

The anticoagulant rule reflects trial data. In CLARITY AD, people taking lecanemab with an anticoagulant had a 2.5% rate of brain hemorrhage larger than 1 cm (2 of 79), against none among those on placebo. Antithrombotic drugs overall, mostly aspirin, did not raise the rate of ARIA.¹

What Is ARIA, and How Serious Is It?

ARIA is an MRI finding that comes in two forms. ARIA-E is edema or effusion: fluid shifting into brain tissue or the spaces around it. ARIA-H is hemosiderin deposition: microhemorrhages or superficial siderosis left by small bleeds. ARIA usually appears early in treatment and usually causes no symptoms. When symptoms occur, they can include headache, confusion, visual changes, dizziness, nausea and trouble walking. Seizures and deaths have occurred.¹

In CLARITY AD, ARIA-E occurred in 12.6% of people on lecanemab, and 2.8% had symptoms.⁵ Brain hemorrhages larger than 1 cm occurred in 0.7% on lecanemab and 0.1% on placebo.¹ In TRAILBLAZER-ALZ 2, ARIA-E occurred in 24.0% on donanemab and 6.1% had symptoms. Three donanemab-treated participants died after serious ARIA.⁴

Because ARIA-E can mimic a stroke, emergency doctors need to know a patient is on one of these drugs before giving a clot-dissolving medicine.¹

How Does APOE4 Change the Risk of ARIA?

APOE4 is the strongest known predictor of ARIA, and the risk rises with each copy. About 15% of people with Alzheimer’s disease carry two copies (homozygotes).¹ For background, see what each APOE genotype means, from e2/e2 to e4/e4.

The pattern holds for symptoms. On lecanemab, symptomatic ARIA-E occurred in 9% of homozygotes, 2% of heterozygotes and 1% of non-carriers, and serious ARIA events in 3% of homozygotes.¹ Both labels carry a boxed warning, the FDA’s most prominent safety warning, stating that homozygotes have higher rates of symptomatic and serious ARIA.^1,2

The labels say APOE4 testing should be done before treatment. A person can decline testing and still be treated, but then no one knows whether they are in the highest-risk group.^1,2

For a homozygote, the decision weighs a modest average benefit against roughly a one-in-three chance of ARIA-E, most of it silent, and a small chance of serious harm. Some people accept that after a full discussion; others decide against it. If you already know you carry APOE4, what to do after a positive APOE4 result covers the steps that come before any treatment decision.

Does Slower Dosing Lower the Risk of ARIA?

For donanemab, yes. In TRAILBLAZER-ALZ 6, 843 participants were randomized to the original schedule or one of three alternatives. A more gradual dose increase cut ARIA-E from 23.7% to 13.7% at 24 weeks, and from 24.2% to 15.6% at 52 weeks, while amyloid removal was nearly identical. In a post hoc look at APOE4 homozygotes, ARIA-E fell from 57.1% to 19.0% at 24 weeks, though that subgroup was small.¹¹

In July 2025, the FDA updated the Kisunla label to make this schedule the recommended one: monthly infusions that start at 350 mg and reach the full 1,400 mg dose at the fourth infusion.²

For lecanemab, no randomized trial has tested a slower start. A 2025 retrospective report from a New York private practice, which Dr. Bilici co-authored, described 19 patients given lecanemab on an APOE-genotype-guided slow titration, which differs from the labeled regimen. ARIA-E and ARIA-H each occurred in 5%, and 26.3% reached plaque clearance. With no control group and few patients, the report points to a question for future trials rather than an answer.¹³

What Changed for Leqembi in 2025 and 2026?

• January 2025: the FDA approved Leqembi IV maintenance every 4 weeks after 18 months of every-2-week infusions, based on modeling of trial data rather than a new trial.¹⁴
• August 2025: Leqembi Iqlik, a subcutaneous autoinjector, was approved for weekly maintenance at home.¹⁰
• July 2026: on July 13, the FDA approved Leqembi Iqlik for starting treatment: 500 mg once weekly, given as two 250 mg injections, with 360 mg weekly for maintenance after 18 months. The approval rested on drug exposure comparable to IV dosing in sub-studies of the CLARITY AD extension, and U.S. availability was planned for late August 2026.¹⁰

Home injection replaces infusion-center visits, not safety monitoring: a baseline MRI and periodic MRIs are still recommended.¹⁰

What Does Treatment Involve Week to Week?

Treatment is a schedule of doses and scans. Leqembi starts with infusions every 2 weeks or weekly injections; Kisunla is a monthly infusion.^1,2,10 Each MRI on the label schedule is reviewed before the next dose, and ARIA findings can pause treatment until the scan improves.^1,2

Kisunla is designed as a limited course. The donanemab recommendations suggest an amyloid PET scan typically 12 to 18 months after starting to decide whether to stop.⁶ In TRAILBLAZER-ALZ 2, 76.4% of all participants on donanemab reached amyloid clearance by 76 weeks.⁴

Medicare covers these drugs for people with MCI or mild Alzheimer’s dementia and documented amyloid when the treating physician takes part in a qualifying registry, a requirement CMS confirmed in July 2023.⁷ Coverage under other plans varies.

Can Leqembi or Kisunla Prevent Alzheimer’s in People Without Symptoms?

Not yet, and neither is approved for that use. A positive amyloid PET or blood test in someone with normal memory and thinking does not meet the labels.^1,2 Two large trials are testing prevention in preclinical Alzheimer’s disease, meaning amyloid without symptoms:

• AHEAD 3-45 (lecanemab): about 1,400 cognitively normal people aged 55 to 80 with intermediate or elevated amyloid. Primary completion is estimated for December 2028.¹⁵
• TRAILBLAZER-ALZ 3 (donanemab): an estimated 2,996 participants with preclinical Alzheimer’s disease. Primary completion is estimated for November 2027.¹⁶

As of October 2026, neither trial has reported efficacy results. Until they do, prevention for a person with normal cognition rests on modifiable risk factors and careful monitoring, not on antibodies.

What Should You Do Next If You Are Considering Treatment?

1. Confirm the stage. Formal cognitive testing establishes whether you are in the MCI or mild dementia range and looks for other contributors, such as medications, sleep apnea, depression, or thyroid and B12 problems.
2. Confirm amyloid with PET, spinal fluid, or a blood test that meets the accuracy bar, interpreted by a specialist.
3. Get APOE genotyping with counseling, and decide in advance how each result would change your choice.
4. Have the MRI reviewed for microbleeds, siderosis, prior strokes and white matter disease.
5. Review your medications, especially anticoagulants, with the doctor who prescribes them.
6. Set expectations. Slower decline is the goal. Plan for the MRI schedule, infusion or injection logistics, and the registry requirement if you have Medicare.

If memory has changed in you or a parent and no one has yet put the pieces together, a neurologist’s memory evaluation is the place to start.

Common Questions

Can I get Leqembi or Kisunla if my amyloid test is positive but I have no symptoms?

No. Both labels limit treatment to MCI or mild dementia due to Alzheimer’s disease. Whether treating at the preclinical stage helps is the question AHEAD 3-45 and TRAILBLAZER-ALZ 3 are designed to answer, and neither has reported results.^1,2,15,16

Will Leqembi or Kisunla improve my memory?

On average, no. In the pivotal trials, both treated groups continued to decline, but more slowly than the placebo groups: 0.45 points less on the CDR-SB over 18 months for lecanemab and 0.67 to 0.70 points less over 76 weeks for donanemab.^3,4

Can APOE4 homozygotes receive Leqembi or Kisunla?

Yes, the labels permit it, but the risk is substantially higher. ARIA-E occurred in 32.6% of homozygotes on lecanemab and 40.6% on donanemab in the pivotal trials.^5,4 The newer donanemab titration lowered that rate in a small post hoc subgroup.¹¹ The decision belongs in a detailed, unhurried conversation.

Can I take aspirin or a blood thinner during treatment?

Aspirin was allowed in the lecanemab trial and did not raise ARIA rates. Anticoagulants are a different matter: the lecanemab recommendations advise against treatment for people who need them, because brain hemorrhage was more common in that group.^1,5 Never stop a blood thinner without talking to the doctor who prescribes it.

What happens if ARIA shows up on an MRI?

It depends on its size and whether it causes symptoms. Under both labels, mild ARIA without symptoms may allow dosing to continue, while moderate or severe ARIA, or ARIA with significant symptoms, leads to a pause until the MRI improves.^1,2 New headache, confusion, visual changes or trouble walking during treatment should prompt a call to your neurologist the same day.

The Bottom Line

Leqembi and Kisunla are the first treatments shown to slow Alzheimer’s disease itself, and the slowing is modest: about 27% to 36% less decline over roughly 18 months in people with MCI or mild dementia.^3,4 They require confirmed amyloid, a suitable MRI and regular scans. Their main risk, ARIA, rises steeply with APOE4, which makes genotyping and an honest conversation part of every decision.^1,2

For people without symptoms, these drugs are not an option yet. The prevention trials are not expected to complete before late 2027.^15,16 If you or a parent is weighing treatment, start with a confirmed diagnosis and a clear picture of what the drug would and would not do for you.

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Dr. Nadir Bilici, MD, DipIBLM, is a board-certified neurologist (ABPN) and Diplomate of the International Board of Lifestyle Medicine specializing in preventive neurology, Alzheimer’s prevention, and cognitive risk assessment. He sees patients by telehealth in the states where he is licensed, with in-person appointments available on a select basis.

References

1. Eisai Inc. LEQEMBI (lecanemab-irmb) injection, for intravenous or subcutaneous use. Prescribing information. Revised January 2026. accessdata.fda.gov/drugsatfda_docs/label/2026/761269s011lbl.pdf
2. Eli Lilly and Company. KISUNLA (donanemab-azbt) injection, for intravenous use. Prescribing information. Revised July 2025. accessdata.fda.gov/drugsatfda_docs/label/2025/761248s004lbl.pdf
3. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948
4. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512-527. doi:10.1001/jama.2023.13239
5. Cummings J, Apostolova L, Rabinovici GD, et al. Lecanemab: appropriate use recommendations. J Prev Alzheimers Dis. 2023;10(3):362-377. doi:10.14283/jpad.2023.30
6. Rabinovici GD, Selkoe DJ, Schindler SE, et al. Donanemab: appropriate use recommendations. J Prev Alzheimers Dis. 2025;12(5):100150. doi:10.1016/j.tjpad.2025.100150
7. Centers for Medicare & Medicaid Services. Statement: broader Medicare coverage of Leqembi available following FDA traditional approval. Published July 6, 2023. cms.gov/newsroom/press-releases/statement-broader-medicare-coverage-leqembi-available-following-fda-traditional-approval
8. U.S. Food and Drug Administration. FDA approves treatment for adults with Alzheimer's disease. Published July 2, 2024. fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease
9. Andrews JS, Desai U, Kirson NY, et al. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials. Alzheimers Dement (N Y). 2019;5:354-363. doi:10.1016/j.trci.2019.06.005
10. Eisai Co., Ltd., Biogen Inc. FDA approves LEQEMBI IQLIK (lecanemab-irmb) subcutaneous injection as an initiation dose for early Alzheimer's disease. Press release. July 13, 2026. media-us.eisai.com/2026-07-13-FDA-Approves-LEQEMBI-IQLIK-R-lecanemab-irmb-Subcutaneous-Injection-as-an-Initiation-Dose-for-Early-Alzheimers-Disease
11. Wang H, Serap Monkul Nery E, Ardayfio P, et al. Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction. Alzheimers Dement. 2025;21(4):e70062. doi:10.1002/alz.70062
12. Palmqvist S, Whitson HE, Allen LA, et al. Alzheimer's Association clinical practice guideline on the use of blood-based biomarkers in the diagnostic workup of suspected Alzheimer's disease within specialized care settings. Alzheimers Dement. 2025;21(7):e70535. doi:10.1002/alz.70535
13. Mervosh N, Bilici N, Wisniewski T, Devi G. Reducing ARIA risk in Alzheimer's disease: real-world impact of genotype-guided slow titration with aducanumab and lecanemab. J Alzheimers Dis. 2025;107(4):1400-1403. doi:10.1177/13872877251366657
14. Eisai Co., Ltd., Biogen Inc. FDA approves LEQEMBI (lecanemab-irmb) IV maintenance dosing for the treatment of early Alzheimer's disease. Press release. January 26, 2025. media-us.eisai.com/2025-01-26-FDA-Approves-LEQEMBI-R-lecanemab-irmb-IV-Maintenance-Dosing-for-the-Treatment-of-Early-Alzheimers-Disease
15. AHEAD 3-45 study: a study to evaluate efficacy and safety of treatment with lecanemab in participants with preclinical Alzheimer's disease and elevated amyloid and also in participants with early preclinical Alzheimer's disease and intermediate amyloid. ClinicalTrials.gov identifier: NCT04468659. Accessed October 28, 2026. clinicaltrials.gov/study/NCT04468659
16. A donanemab (LY3002813) study in participants with preclinical Alzheimer's disease (TRAILBLAZER-ALZ 3). ClinicalTrials.gov identifier: NCT05026866. Accessed October 28, 2026. clinicaltrials.gov/study/NCT05026866

Written and medically reviewed by Nadir Bilici, MD, DipIBLM. Published October 2026 · Medically reviewed on October 13, 2026. See our editorial policy.