Lecanemab and Donanemab: A Patient's Guide to the New Alzheimer's Treatments

The 2023 approval of lecanemab (Leqembi) and the 2024 approval of donanemab (Kisunla) represent the first meaningful advance in Alzheimer's disease-modifying therapy in decades. The way they are discussed online often oversimplifies — either overstating the benefits or dismissing them entirely. This article is a patient-level walkthrough of what the medications actually do, who qualifies, what the risks are, and how to think about whether they make sense for a specific person.

The basic picture

For the first time since 2003, medications have been approved that affect the underlying biology of Alzheimer's disease rather than just the symptoms. Older Alzheimer's medications (cholinesterase inhibitors, memantine) are symptomatic — they compensate for lost neurotransmitter function temporarily. Lecanemab and donanemab are disease-modifying — they remove amyloid plaques, which is part of the underlying pathology.

The effect is real but modest:

• 25 to 35 percent slower decline on cognitive and functional measures over 18 months compared to placebo
• In individual experience, this typically means a few additional months of maintained function
• The disease continues to progress; it does not stop
• Existing cognitive impairment is not reversed

These are not cures. They are the first incremental win in a disease that has frustrated drug development for decades. Whether the incremental win is worth the risk and burden for a specific person is the question the medications raise.

How they work

Both lecanemab and donanemab are monoclonal antibodies — laboratory-designed antibodies that bind specifically to beta-amyloid, the protein that accumulates in Alzheimer's plaques. When the antibody binds amyloid, the body's immune system clears it from the brain.

The underlying theory — the amyloid hypothesis of Alzheimer's disease — proposes that amyloid accumulation is central to the disease process. Lecanemab and donanemab are the first therapies that effectively remove amyloid in living patients and the first to translate that removal into clinical benefit.

Important context: removing amyloid slows the disease modestly rather than dramatically. This suggests that amyloid is important but not the entire story — other processes (tau tangles, neuroinflammation, vascular contributions) also matter. Future treatments targeting multiple pathways may be more effective than amyloid removal alone.

Who qualifies

Eligibility is more specific than most people assume.

Required features

• Diagnosis of mild cognitive impairment due to Alzheimer's disease OR mild Alzheimer's dementia. The treatments are approved for early-stage disease only — not for moderate or severe Alzheimer's, and not for non-Alzheimer's dementias.

• Confirmed amyloid pathology. Amyloid presence must be documented, typically by:

  • Amyloid PET scan showing amyloid plaques
  • Cerebrospinal fluid analysis showing patterns consistent with Alzheimer's
  • Newer blood-based biomarkers may eventually qualify (p-tau217 and similar tests), though this is evolving

• Brain MRI without significant contraindications. Specifically:

  • No more than a few microbleeds on baseline MRI (typically fewer than 5 for lecanemab)
  • No significant cortical siderosis or significant strokes
  • No other contraindications (tumors, significant vascular malformations)

• Ability to tolerate regular infusions and MRI monitoring. Someone who cannot cooperate with IV placement, cannot tolerate MRI, or cannot reliably attend scheduled visits is typically not a candidate.

• Ability to provide informed consent (or have a legal decision-maker who can).

Typically not candidates

• Moderate or severe Alzheimer's disease — too far along for current evidence of benefit
• Non-Alzheimer's dementias — Lewy body, frontotemporal, vascular dementia without significant Alzheimer's component
• Recent significant cerebrovascular events — stroke, significant microbleeds
• People on dual antiplatelet therapy or anticoagulants with high bleeding risk — must be evaluated carefully
• APOE ε4 homozygotes — can still receive treatment but have significantly higher ARIA risk, requiring careful discussion

APOE status matters

APOE is a gene that affects Alzheimer's risk. Everyone has two copies. People who carry two ε4 copies (about 2-3% of the population) have the highest Alzheimer's risk and also the highest ARIA risk with amyloid-targeting therapies. Guidelines recommend APOE testing before starting these treatments, and the specific genotype affects:

• The expected benefit (somewhat similar across genotypes)
• The expected risk of ARIA (significantly higher in ε4 homozygotes)
• Sometimes the treatment plan (adjusted monitoring frequency or shared decision-making)

What to expect during treatment

Before starting

Pre-treatment workup typically includes:

• Confirmation of diagnosis — detailed evaluation including cognitive testing, family history, and often neuropsychological battery
• Amyloid confirmation — PET or CSF testing
• Brain MRI — baseline imaging to rule out contraindications and establish a reference
• APOE genotype testing — to assess ARIA risk
• Pre-treatment discussion — typically at least one detailed visit to discuss risks, benefits, logistics, and expectations
• Insurance authorization — often a lengthy process involving pre-authorization and specific documentation

Starting treatment

First infusions are typically done in a supervised infusion center. You can expect:

• A 1-hour IV infusion for lecanemab, similar or slightly longer for donanemab
• Monitoring during and after for infusion reactions
• Regular visits with the neurologist to track tolerance
• No major immediate changes in cognition — the medications work over months, not days

MRI monitoring

A distinctive feature of these medications:

• Baseline MRI before starting
• Monitoring MRIs at specific intervals (approximately before infusions 5, 7, and 14 for lecanemab)
• Additional MRIs if symptoms suggest possible ARIA

The monitoring identifies ARIA in asymptomatic people before it becomes clinically significant. MRI frequency may be adjusted based on initial findings and APOE status.

Ongoing treatment

• Regular infusions — every 2 weeks for lecanemab, every 4 weeks for donanemab
• Symptom monitoring — any new headache, confusion, vision changes, or weakness should prompt a call to the treating team
• Cognitive reassessment — typically at 6-month intervals during treatment
• Decision-making about continued treatment — whether to continue is periodically reassessed based on response and tolerability

Duration of treatment

For lecanemab, the pivotal clinical trial studied 18 months of treatment. Real-world treatment may continue for longer periods, with decisions based on ongoing assessment. For donanemab, the clinical trial incorporated a protocol to stop treatment when amyloid was sufficiently cleared — which for some patients happened at 12 months, for others longer.

These decisions evolve as more real-world evidence accumulates.

ARIA — the main risk to understand

ARIA (amyloid-related imaging abnormalities) is the most important side effect to understand.

Types

ARIA-E (edema) — swelling in an area of the brain, typically asymptomatic. Seen on MRI as fluid accumulation.

ARIA-H (hemorrhage) — small areas of brain bleeding. Usually small (microbleeds) but occasionally larger.

Some people experience both types simultaneously.

Frequency

• Overall ARIA incidence with lecanemab: approximately 20-25% of treated patients
• Overall ARIA incidence with donanemab: slightly higher, roughly 25-35%
• Symptomatic ARIA (causing actual symptoms): approximately 3-5% of treated patients
• Severe ARIA (causing significant neurological injury or requiring hospitalization): uncommon but real
• Fatal ARIA: rare but has occurred, particularly in APOE ε4 homozygotes and in patients on anticoagulation

Risk factors

• APOE ε4 carrier status, particularly homozygotes
• Anticoagulation (blood thinners) increases hemorrhagic ARIA risk
• Pre-existing microbleeds on baseline MRI
• Dual antiplatelet therapy (aspirin plus clopidogrel, etc.)

When to seek urgent evaluation

Any of these during treatment warrants immediate contact with the treating team:

• New headache, especially severe or persistent
• New confusion or cognitive decline
• Vision changes
• Weakness on one side
• Seizures
• Trouble speaking

These can represent ARIA or other neurological events and need prompt assessment.

Management

Most asymptomatic ARIA is managed by continuing treatment with closer MRI monitoring; some cases require temporary suspension. Symptomatic or severe ARIA typically requires discontinuation and supportive care. The treating neurologist guides decisions.

Other side effects

Infusion reactions

Fever, chills, rash, or other symptoms during or shortly after infusion. Managed with pre-medication (acetaminophen, sometimes antihistamines) and slower infusion rates. Usually mild and manageable.

Headache

Common but usually transient.

Nausea, fatigue, falls

Reported by some patients; relationship to the medication is variable.

Allergic reactions

Rare but possible; treated like other allergic reactions.

The decision — is it worth it?

This is the central question, and there is no universal answer. Considerations:

Arguments for treatment

• First disease-modifying therapy for Alzheimer's — meaningful biological progress
• Measurable slowing of decline (25-35% over 18 months)
• Possible added months of higher-functioning life
• Some research supports additional brain volume preservation beyond the cognitive measures
• May extend the window for other interventions that emerge in coming years
• Affects the underlying disease rather than just symptoms

Arguments against or for caution

• Real but rare risk of severe or fatal ARIA
• Substantial time commitment — bi-weekly or monthly infusions for 18+ months
• Regular MRI monitoring — typically several MRIs in the first year
• Out-of-pocket costs even with insurance
• Modest rather than transformative benefit — a few months of preserved function, not a cure
• Uncertain long-term benefit beyond 18 months
• Higher risk in APOE ε4 homozygotes requiring careful weighing

Who tends to benefit most

• Very early disease — MCI or very mild dementia stage
• Preserved function in daily activities
• Strong family and logistical support to attend regular visits
• Non-APOE ε4 homozygote (lower ARIA risk)
• No significant anticoagulation needs
• Clear commitment to the time and monitoring

Who might reasonably decline

• Already in moderate or later dementia (not eligible)
• Severe comorbidities that make the time burden disproportionate
• APOE ε4 homozygotes who want to avoid the higher ARIA risk
• Patients on necessary anticoagulation that cannot be safely adjusted
• Limited access to monitoring facilities (the MRI burden is real)
• Personal values that favor quality of time over extension of a given functional level
• Caregiver constraints that make the time commitment impractical

Questions to ask

If you or a family member is considering these medications, questions worth preparing:

• Is the Alzheimer's diagnosis definitively confirmed with amyloid testing?
• What is my APOE genotype and how does it affect my ARIA risk?
• What is the specific expected benefit for me, given my stage?
• What do my brain MRI findings look like — any contraindications or risk factors?
• How will we monitor for ARIA and what is the plan if it develops?
• What is the infusion schedule and what will my life look like during treatment?
• What does insurance cover, and what will I pay out of pocket?
• How will we measure whether the treatment is helping?
• When would we stop treatment — and how is that decision made?
• What symptoms should prompt immediate contact with the team?

The bigger picture

Lecanemab and donanemab are meaningful but incremental. They demonstrate that amyloid removal translates to clinical benefit, which validates decades of research. They are not cures. Future treatments — targeting tau, targeting neuroinflammation, combining approaches — may be more effective. Current treatment decisions are made within the landscape as it exists, not the landscape as it might exist in 5 or 10 years.

For eligible patients, the decision is personal. Many patients and families choose treatment; many reasonably decline. There is no clearly right answer for everyone. A detailed conversation with a neurologist who sees many of these patients is the right path to a decision.

A note on access

Access to these medications varies significantly by geography. Urban centers with established memory clinics and infusion facilities offer them readily; many rural areas do not have easy access. Some patients travel significant distances for initial evaluation and then work with local infusion centers. The Alzheimer's Association and major academic centers can help identify treatment options in specific regions.

Resources

• Alzheimer's Association has detailed resources on lecanemab and donanemab at alz.org
• A behavioral neurologist or specialized memory clinic for eligibility assessment and treatment
• The manufacturer patient assistance programs (Eisai for lecanemab, Eli Lilly for donanemab) may help with access and costs
• Your state's Area Agency on Aging for broader support navigating dementia care

Related reading

• Dementia Medications: What Actually Helps, Explained
• Alzheimer's Disease: A Complete Guide
• Mild Cognitive Impairment (MCI): Is It Dementia?
• Can Dementia Be Reversed or Cured?
• Is Dementia Hereditary?

References

• van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. New England Journal of Medicine. 2023;388(1):9–21.
• 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.
• Centers for Medicare & Medicaid Services. National Coverage Determination — Monoclonal Antibodies Directed Against Amyloid.
• Cummings J, Apostolova L, Rabinovici GD, et al. Lecanemab: Appropriate Use Recommendations. Journal of Prevention of Alzheimer's Disease. 2023;10(3):362–377.

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Disclosure: Dr. Shimada is the founder of Tokei Health. This article is informational and is not a substitute for individual medical advice from your own clinician.