Lecanemab and Donanemab for Alzheimer's: Who Qualifies?

Research-informed explainer — last updated April 12, 2026

Lecanemab (Leqembi) and donanemab (Kisunla) are the first drugs approved by the FDA to demonstrably slow the progression of Alzheimer's disease in its early stages. Both work by clearing amyloid plaques from the brain. Both showed statistically significant effects in large randomized trials. Both carry a serious risk of brain swelling and microbleeds called ARIA. And both are appropriate only for a narrow population: people with confirmed amyloid pathology and mild cognitive impairment or mild Alzheimer's dementia. Understanding who actually qualifies -- and what the trade-off between modest benefit and real risk looks like -- is essential before starting treatment.

This explainer draws on research from five specialists in the Convene directory. Jeffrey Cummings at UNLV developed the Montreal Cognitive Assessment (MoCA), the standard cognitive screening tool used to determine whether a patient is in the early disease stage required for eligibility. Reisa Sperling at Harvard led the landmark work defining preclinical Alzheimer's and has served as principal investigator on the A4 Study screening presymptomatic patients. Ronald Petersen at Mayo Clinic defined mild cognitive impairment -- the primary target population for both drugs -- in research cited nearly 8,000 times. William Jagust at UC Berkeley contributed to the A/T/N biomarker framework used to confirm amyloid-positive status before initiating therapy. Bradley Boeve at Mayo Clinic has published extensively on how frontotemporal dementia and related non-Alzheimer's dementias are distinguished from Alzheimer's disease -- a critical step in identifying who should not receive these drugs.

What lecanemab and donanemab are

Both drugs are monoclonal antibodies administered by intravenous infusion. They bind to amyloid-beta in the brain and promote its clearance. Lecanemab preferentially targets soluble amyloid protofibrils; donanemab targets a modified form of amyloid called pyroglutamate amyloid. Both have received full FDA approval for early Alzheimer's disease.

The core clinical trial data:

Lecanemab (CLARITY-AD, n=1,795): 27% slowing of clinical decline on the primary endpoint (CDR-SB scale) over 18 months compared to placebo. Complete amyloid clearance in a majority of treated patients by 18 months. ARIA-edema occurred in 12.6% of treated patients (vs. 1.7% placebo); ARIA-microhemorrhages in 17.3%.

Donanemab (TRAILBLAZER-ALZ 2, n=1,736): 35% slowing of decline in patients with low-to-medium tau burden; 22% in the full population. Treatment was designed to stop when amyloid was cleared (most patients by 12 months). ARIA-edema in 24% of treated patients; ARIA-microhemorrhages in 31.4%.

Who qualifies: the eligibility requirements

Access to these drugs is tightly constrained by the eligibility criteria used in the trials, which are now reflected in the approved indications and in payer coverage requirements.

Cognitive stage: Both drugs are indicated for patients with mild cognitive impairment (MCI) due to Alzheimer's disease or mild Alzheimer's dementia -- not moderate or severe dementia. Ronald Petersen's foundational work defining MCI as a distinct diagnostic entity established the clinical framework that all current Alzheimer's trials use for enrollment [6]. Patients with more advanced disease were excluded from both trials because the benefit-risk calculation changes substantially when neurodegeneration is already severe.

Confirmed amyloid pathology: This is the non-negotiable eligibility gate. Patients must have confirmed amyloid in the brain before treatment can start, demonstrated by either amyloid-PET imaging or cerebrospinal fluid biomarkers (low amyloid-42 and/or elevated phosphorylated tau). The A/T/N biomarker framework that William Jagust and colleagues contributed to development of provides the scientific basis for this requirement [9]. Treating amyloid-negative patients provides no benefit and still carries the full ARIA risk.

Genetic screening: APOE4 carriers have substantially higher ARIA risk. Homozygous APOE4 carriers (two copies of the risk gene) face the highest rates of ARIA events -- in donanemab trials, symptomatic ARIA occurred in over 40% of APOE4/4 homozygotes. Most clinical practices now perform APOE genotyping before initiating treatment to inform the risk discussion and may decline to treat high-risk patients or use modified dosing protocols.

Age and comorbidities: The trials primarily enrolled patients aged 50 to 90. Patients with significant cerebrovascular disease, anticoagulant use, or a history of multiple microhemorrhages on MRI face amplified ARIA risk. An MRI before starting treatment is required to establish a baseline and screen for pre-existing pathology.

Diagnosing early Alzheimer's accurately: why it matters

One of the most important gatekeeping functions in this new treatment landscape is making sure the patient actually has Alzheimer's and not a different dementia. Bradley Boeve's research on frontotemporal dementia and related conditions -- including the C9ORF72 mutation that causes FTD/ALS -- defines the non-Alzheimer's dementias that must be ruled out [12]. Misdiagnosis could lead to treatment with drugs that won't help and carry serious risks.

Cognitive assessment tools like the MoCA, developed by Jeffrey Cummings and colleagues [1], provide a standardized quantitative measure of cognitive function. A MoCA score is not sufficient alone to diagnose Alzheimer's -- biomarker confirmation is required -- but it establishes whether the patient is in the appropriate cognitive stage for treatment eligibility.

The 2024 Alzheimer's Association revised diagnostic criteria, which incorporated recent biomarker evidence, now recognize Alzheimer's as a biological disease entity definable by A/T/N status regardless of cognitive symptoms [11]. This framework is important for understanding who may eventually become eligible as treatments move earlier in the disease process.

Understanding ARIA: the main safety risk

ARIA stands for amyloid-related imaging abnormalities. There are two types: ARIA-E (edema, visible as bright areas on fluid-attenuated inversion recovery MRI) and ARIA-H (microhemorrhages, visible as dark spots on susceptibility-weighted MRI). Most ARIA events are asymptomatic and are found on the routine MRI monitoring required for patients on these drugs. Symptomatic ARIA can include headache, confusion, dizziness, and in rare cases seizures.

Most ARIA resolves on its own, and in trials, patients with ARIA-E were typically paused from treatment until imaging cleared. Serious or life-threatening ARIA -- including cases resulting in death -- has occurred, though the absolute risk is low. Three deaths possibly related to ARIA in the lecanemab trial raised concerns that received significant attention.

The monitoring protocol for both drugs requires MRI at defined intervals: before treatment, then at weeks 26 and 52, plus any time symptoms suggest ARIA. This ongoing MRI requirement has practical implications for patients who live far from imaging facilities or have contraindications to MRI.

What "slowing progression" means -- and doesn't mean

It is important to be clear about what these trials demonstrated. A 27 to 35% slowing of decline means that over 18 months, the treated group declined less than the placebo group on a cognitive-functional scale. The treated patients still declined. The drugs do not halt the disease or reverse existing damage. The scale points translate into an estimated delay in progression of roughly four to seven months over the 18-month trial period.

Whether that delay is meaningful in daily life is a reasonable question, and different patients will answer it differently. Patients and families who prioritize any delay in cognitive decline will view this as significant. Others may weigh the infusion burden, monitoring requirements, ARIA risk, and cost against a modest symptomatic benefit and conclude the trade-off does not work for them.

Cost and access

Both drugs carry list prices exceeding $26,000 per year. Medicare coverage requires amyloid confirmation (PET or CSF), treatment by a participating neurologist, and enrollment in the Alzheimer's Association registry. Many Medicare beneficiaries face significant cost-sharing. Commercial insurance coverage varies. Access is concentrated at academic medical centers and memory clinics -- patients in rural or underserved areas may face substantial barriers to amyloid PET imaging and to neurologists experienced with ARIA monitoring.

What comes next

Clinical trials are now exploring whether these or similar drugs might work even earlier -- in the preclinical stage before any cognitive symptoms appear. Reisa Sperling's A4 Study and the ongoing AHEAD trial test anti-amyloid approaches in cognitively normal amyloid-positive adults [3]. These studies may eventually shift the treatment window earlier than the current early MCI indication if they demonstrate benefit without unacceptable risk.

Questions to ask your doctor

• Based on my cognitive testing and biomarker results, am I in the right disease stage to qualify for lecanemab or donanemab?
• What is my APOE4 status, and how does it affect the risk of ARIA for me specifically?
• What does the monitoring protocol look like -- how often do I need MRI, and what happens if ARIA is found?
• What is a realistic description of the benefit I might expect from 18 months of treatment?
• Are there clinical trials I could join that might be appropriate for my disease stage?
• What are the practical logistics of infusion -- how often, how long, and at what facility?