What to Expect Along the Anti-Amyloid Therapy Pathway


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This guide outlines the anti-amyloid therapy pathway in the sequence you'll experience it, setting clear expectations for each step, what gets checked, and actions to take if symptoms arise. While anti-amyloid therapy may modestly slow early Alzheimer's disease decline, it is not a cure and does not restore lost memory.

Step 1 - Confirm the Diagnosis (Biology First)

What happens

Your care team determines if your symptoms are due to Alzheimer’s disease biology.

What tests are used

You may undergo one or more of the following tests:

  • CSF (spinal fluid) testing to confirm amyloid positive (A+) and tau positive (T+)

  • Amyloid PET and sometimes tau PET in research settings

  • Blood biomarkers as screening or supportive evidence, depending on clinical context

Why this step matters

Anti-amyloid therapy is suitable only when Alzheimer's disease biology is verified. This step confirms the specific cause of your symptoms, preventing treatment of the wrong condition.

Step 2 - Confirm You Are in the Right Stage for Treatment

What happens

Your care team ensures that your impairment stage aligns with the stage where anti-amyloid therapy may be beneficial.

What this typically includes

  • Clinical assessment of daily function

  • Cognitive screening and/or formal testing

  • Review of symptom timeline and safety considerations

Why this step matters

Anti-amyloid therapy is designed for early Alzheimer’s disease, not moderate or advanced dementia.

Step 3 - Safety Screening: Confirm Your Personal Risk Profile

Your care team evaluates the risk of side effects, particularly ARIA (amyloid-related brain swelling or bleeding). This is a crucial safety step in the entire pathway.

3A - Medical history review

Your team reviews:

  • Prior stroke or TIA

  • Prior brain bleed or head trauma

  • Seizure history

  • Chronic headaches or migraine patterns

  • Autoimmune/inflammatory disease

  • Active malignancy or recent chemotherapy

  • Kidney/liver disease

  • Blood pressure control and vascular risk factors

3B - Medication review (high impact)

Your team reviews everything you take, including over-the-counter medications and supplements, focusing on:

  • Anticoagulants (blood thinners)

  • Antiplatelet agents

  • Frequent or chronic NSAID use

  • Immunomodulating or disease-modifying agents (when relevant)

Medication risk does not always mean “no.” It may mean adjusting the plan, increasing monitoring, or reconsidering whether therapy is worthwhile.

3C - MRI safety screening (critical)

You will need a recent MRI including SWI/SWAN sequences to detect:

  • Cerebral microbleeds (CMBs)

  • Evidence of prior silent hemorrhage

  • White matter disease burden (WMD)

  • Findings suggestive of CAA (cerebral amyloid angiopathy)

These imaging findings are strong predictors of ARIA risk.

3D - Genetics (APOE) risk discussion

You may be offered APOE testing since APOE status can impact ARIA risk:

  • APOE ε4 carriers often have a higher risk of ARIA, especially early in therapy

  • APOE is not destiny; it helps tailor monitoring and informed consent

Output of Step 3

At the end of this step, your provider should inform you about:

  • Whether you are a suitable candidate for treatment

  • Your personal risk level for ARIA and other complications

  • Your planned monitoring schedule

Step 4 - Treatment Choice: Lecanemab vs Donanemab

Your provider will recommend a medication based on safety, access, and clinical fit.

Lecanemab

  • Infusion frequency: usually every 2 weeks

  • Often treated as a steady, ongoing therapy

Donanemab

  • Infusion frequency: usually every 4 weeks

  • Often used with a strategy of treating until amyloid is sufficiently reduced, then reassessing whether therapy can pause or stop

Both require structured MRI monitoring and ongoing follow-up.

Step 5 - Insurance Authorization and Scheduling

What happens

Your team submits documentation to insurance, typically including:

  • Diagnosis confirmation (A+ / T+ evidence)

  • Cognitive stage documentation

  • Baseline MRI safety review

  • Baseline cognitive test scores

What to expect

  • Many patients have medication coverage approved, but copays vary

  • You may incur standard copays for clinic visits, imaging, and infusion services depending on your plan

Once approved, your infusion schedule and baseline monitoring calendar are set.

Step 6 - Infusion Start: What the First 3 Months Usually Look Like

Pre-medications (common early strategy)

To reduce infusion reactions (flu-like symptoms or mild allergic reactions), many patients receive:

  • Low-dose steroid

  • Antihistamine
    Often for the first ~3 months, then tapered if tolerated.

What you may feel after infusion

Common short-term effects can include:

  • Fatigue

  • Mild headache

  • Lightheadedness

These are usually manageable.

Step 7 - Symptoms to Watch For (Your Action Plan)

Mild symptoms (often monitored at home)

  • Mild headache

  • Mild fatigue

  • Mild dizziness

Your provider may advise avoiding NSAIDs unless specifically approved. Examples include ibuprofen (Advil/Motrin) and naproxen (Aleve).

Urgent symptoms (contact your provider immediately)

  • Severe headache (especially >7/10)

  • Headache lasting >12-24 hours

  • New confusion or sudden worsening of thinking

  • Stroke-like symptoms (weakness, numbness, speech difficulty, vision changes)

  • Seizure-like symptoms

What to do if urgent symptoms occur

  • Send a message through the patient portal AND call your clinic/infusion team

  • If symptoms are severe or persistent, go to the emergency department

Do not try to "wait it out" if symptoms are significant.

Step 8 — MRI Monitoring for ARIA (What Happens and When)

MRI monitoring is a required safety component of anti-amyloid therapy. These scans are used to screen for ARIA, which stands for Amyloid-Related Imaging Abnormalities. ARIA can occur with or without symptoms, which is why scheduled imaging is mandatory even when you feel well.

There are two main types:

  • ARIA-E: brain swelling (edema)

  • ARIA-H: brain bleeding (microbleeds or hemorrhage)

The risk of ARIA is highest early in treatment, which is why MRI monitoring is front-loaded during the first several months.


Step 8A — Baseline MRI (Before Any Infusion)

What happens
Before starting therapy, you must have a recent brain MRI that includes:

  • Standard structural sequences

  • SWI or SWAN sequences to detect bleeding risk

What your provider reviews

  • Cerebral microbleeds (CMBs)

  • White matter disease (WMD)

  • Evidence of cerebral amyloid angiopathy (CAA)

  • Prior silent hemorrhage

Why this matters
Baseline MRI findings strongly influence:

  • Whether it is safe to start treatment

  • How closely you will be monitored

  • Whether additional MRIs may be needed beyond the standard schedule


Step 8B — Scheduled MRI Monitoring (Medication-Specific)

After treatment begins, MRIs are scheduled at specific infusion milestones. These scans are reviewed before the next infusion proceeds.


Lecanemab (Leqembi) — Required MRI Schedule

If you are receiving lecanemab, expect MRIs at the following points:

  1. Baseline MRI — before your first infusion

  2. MRI before the 3rd infusion

  3. MRI before the 5th infusion

  4. MRI before the 7th infusion

  5. MRI before the 14th infusion

Key notes

  • These MRIs are typically performed within ~1 week before the scheduled infusion

  • Infusions may be held until MRI results are reviewed

  • Additional MRIs may be ordered if you are at higher risk (e.g., APOE ε4 carrier, more baseline microbleeds)


Donanemab (Kisunla) — Required MRI Schedule

If you are receiving donanemab, expect MRIs at the following points:

  1. Baseline MRI — before your first infusion

  2. MRI before the 2nd infusion

  3. MRI before the 3rd infusion

  4. MRI before the 4th infusion

  5. MRI before the 7th infusion

Key notes

  • ARIA risk with donanemab is also highest in the early months

  • Close monitoring is emphasized during the first ~24 weeks

  • Your provider may recommend additional MRIs later in treatment depending on risk profile


Step 8C — Symptom-Triggered MRI (Any Time)

Regardless of medication or schedule, an urgent MRI is required if you develop symptoms concerning for ARIA.

Symptoms that trigger immediate imaging

  • New or severe headache (especially >7/10)

  • Headache lasting longer than 12–24 hours

  • New confusion or cognitive change

  • Stroke-like symptoms (weakness, numbness, speech or vision changes)

  • Seizure-like symptoms

If these occur:

  • Message your provider immediately

  • Call the clinic or infusion team

  • Go to the emergency department if symptoms are severe or persistent

Do not wait for your next scheduled MRI.


Step 8D — What Happens If ARIA Is Found

If ARIA is detected on MRI, your care team will decide next steps based on severity and symptoms.

  • Mild ARIA

    • Often monitored with repeat MRI

    • Infusions may continue or pause briefly

  • Moderate ARIA

    • Infusions are usually paused

    • Repeat MRIs are performed until resolution

  • Severe ARIA

    • Infusions are stopped

    • Additional neurologic evaluation and monitoring are required

Most ARIA cases resolve with monitoring and temporary pauses. Serious complications are uncommon but taken seriously.

Step 9 - Ongoing Follow-Up: The "Rhythm" of Treatment

Every 3 months: clinical check-in

Expect a structured review of:

  • Side effects and symptoms

  • Daily function and safety

  • New medications started by other providers

  • Whether the benefit-risk balance still makes sense

Periodic blood biomarkers (provider-specific)

Some clinicians monitor markers such as:

  • p-tau181

  • p-tau217

  • GFAP

  • NfL

These do not "prove" benefit on their own, but can support biological tracking and safety surveillance.

Step 10 - Cognitive Monitoring and Insurance Continuation

Every 6 months

Many insurers require updated cognitive screening for continued coverage, often with:

  • MoCA or MMSE
    Results may need to be uploaded for authorization renewal.

Every 12 months

Expect formal repeat cognitive testing to evaluate longer-term trajectory.

If cognitive impairment progresses beyond a stage where benefit is expected or coverage is allowed, your provider will assess whether continuing is still appropriate. This conversation is part of responsible care.

Step 11 - Amyloid PET Follow-Up and Long-Term Plan (Often 12-18 Months)

What happens

Some pathways include repeat amyloid PET around 12-18 months to quantify amyloid reduction.

Goals often discussed

  • Amyloid reduction toward low levels (commonly <25 Centiloids)

  • Stabilization or improvement of tau-related biomarkers when possible

What decisions can follow

  • Continue therapy as-is

  • Adjust dosing strategy

  • For donanemab, consider pausing or stopping after adequate amyloid reduction

  • Consider future options, including subcutaneous formulations if/when available and appropriate

Step 12 - When Therapy Is Paused or Stopped

Therapy may be paused or stopped due to:

  • ARIA that does not resolve or recurs at concerning severity

  • Major brain bleeding or serious neurological complications

  • New stroke or major neurological event

  • Medication changes that substantially increase bleeding risk

  • Progression to a stage where benefit is unlikely or coverage is no longer supported

Stopping therapy is a clinical decision based on safety and realistic benefit, not failure.

The Core Message to Hold Onto

Anti-amyloid therapy is a long-term, monitored process. It may modestly slow decline in early Alzheimer's disease for some, but it is not a cure and does not restore lost memory. The pathway is designed to be safe, structured, and revisited over time so that treatment continues only as long as the benefit-risk balance remains acceptable.