Alzheimer Therapeutic Program

Patients undergo an evaluation by ATP clinicians to determine if they may receive treatment with lecanemab or donanemab. This assessment involves gathering information from the patient, their doctors and caregivers (care partners) about symptoms, everyday functioning, and other medical information (diagnoses, medications, etc.), a short cognitive test, neurological exam, and review of their brain MRI. Specialized Alzheimer Disease testing, including an amyloid positron emission topography (PET) scan or lumbar puncture, is also required, as is a genetic test for apolipoprotein E (APOE).

The e4 variant of the APOE gene increases the risk of having treatment-related side effects, including swelling and bleeding in the brain. This risk is highest in patients with two copies of the e4 variant. This treatment-specific evaluation takes place over one to three visits within a few weeks. Some patients may be ineligible for treatment once this data has been reviewed, usually because of concerns about safety or low likelihood of clinical benefit.

Patients eligible for lecanemab and/or donanemab and their care partners are provided a clinical overview of these medications to help inform their decision about whether to receive the treatment. This discussion includes how these medications work, their potential benefits and side effects, safety planning and monitoring, and an overview of the ATP structure and how to contact our team. Risk assessments are personalized based on APOE genetic testing results and other clinical factors. We strive to understand patient values, priorities, and goals of treatment, and do our best to ensure treatment works towards these goals. Personalized and well-informed decisions are crucial in helping our patients achieve the best outcome.

Infusion Visits

Lecanemab and donanemab infusions are administered at designated infusion centers, which includes the Brigham and Women's Hospital Main Campus, Brigham and Women's Faulkner Hospital, Mass General Hospital and Mass General Brigham Healthcare Center (Waltham). Lecanemab is administered every two weeks; donanemab is every 4 weeks. Following each infusion, there is an observation period to monitor for immediate side effects. The observation window is longest after the first few infusions and shortens with later infusions.

MRI Monitoring

Brain MRIs are required during the first 6 months of treatment with lecanemab and donanemab. For lecanemab, the MRIs take place before the 5th, 7th and 14th infusions. For donanemab, the MRIs take place before the 2nd, 3rd, 4th, and 7th infusions. These MRIs asses for areas of swelling and/or bleeding in the brain, collectively known as amyloid-related imaging abnormalities (ARIA), which can occur in patients taking either lecanemab or donanemab. If patients report new symptoms, additional MRIs may be recommended.

Phone Check-Ins

Patients receive periodic phone calls from the ATP staff for symptom monitoring. These may take place before (e.g., screen for symptoms suggestive of ARIA) or after an infusion (e.g., screen for symptoms suggestive of an infusion reaction). Patients are always encouraged to proactively reach out to the ATP with new symptoms or if there are other changes in their health or medications.

Follow-Up Visits

In addition to infusion visits, ATP patients will follow up in the clinic for check-up every six months. Additional office visits may be needed in some cases.

ATP Clinic Care Model

The ATP is staffed by a rotating team of neurologists with subspecialty expertise in Alzheimer disease. Once a patient has established care within the ATP, there are multiple ways to contact our team, including telephone during work hours and patient portal messaging; for emergencies, the ATP on-call clinician be reached via direct page 24 hours per day, 7 days per week. ATP provides specialized care specifically related to lecanemab and donanemab. Alzheimer care that does not directly relate to these medications must be provided by the patient’s referring clinician.

The FDA has set guidelines on who will be eligible to receive this treatment, summarized in the FDA label. Only individuals who meet these guidelines­ will be evaluated to receive it; for safety reasons, some individuals will be ineligible to receive this treatment. Experts in the field have also published an article documenting appropriate use recommendations. Broadly speaking, it is approved for patients with early-stage cognitive impairment due to Alzheimer disease who are otherwise free of contraindications. Early-stage cognitive impairment is defined as mild cognitive impairment: cognitive decline that does interfere with a person’s independent daily functioning, or mild dementia: cognitive impairment that causes a loss of independence in complex daily activities (e.g., paying bills, driving, managing medications) but not for basic daily activities (e.g., bathing, feeding, dressing). To be diagnosed with Alzheimer disease for the purposes of lecanemab eligibility, a specific biomarker test must be performed, which includes an amyloid PET scan or a lumbar puncture for tests of amyloid and tau.

Some patients and families may decide they do not want to receive this medication for medical, personal, or other reasons. The ATP will discuss alternative care options, including clinical trials.

Lecanemab works by lowering the level of beta-amyloid protein in the brain. This approach does not stop the disease progress nor lead to improvement in symptoms or functional abilities. Rather, it slows the rate of cognitive and functional decline. In the Phase 3 research study, the group treated with lecanemab had a reliable slower decline on cognitive tests and questionnaires assessing functioning in activities of daily living than the group that received a placebo (an approximately 5-month saving over the 18 months of the trial, on average). Not all experts agree on whether this represents a clinically significant difference.

The magnitude of the effect is likely different from person to person.

The Centers for Medicare and Medicaid Services (CMS) has indicated that coverage will be provided to Medicare beneficiaries if they are enrolled in an approved Alzheimer Patient Registry. The medication costs approximately $26,500 a year. The exact cost to beneficiaries will vary by different insurance coverage plans. For example, individuals with Original Medicare will pay the standard 20% coinsurance of the Medicare-approved amount for lecanemab once they meet their Part B deductible, whereas patients with supplemental Medicare plans may have much of this deductible covered. Patients may also be responsible for some costs associated with infusions, MRI scans, health care provider appointments, and other aspects of treatment. Some private health insurance plans have announced plans to cover lecanemab with prior authorization, whereas other plans have not yet provided details.

Patient registries will collect information from providers to help ensure appropriate patient selection and use of anti-amyloid antibody treatments for AD. Data about patient outcomes and safety will be of critical importance and will help us make decisions about future treatment options.

To be considered for treatment, patients must be evaluated for cognitive changes and receive a diagnosis of mild cognitive impairment due to AD or mild AD dementia. The following elements must be completed by a primary care doctor, neurologist, psychiatrist, or other referring provider prior to referral:

• Brief cognitive evaluation within 6 months of referral.
• MRI of brain within 12 months of referral.
• Basic lab tests within 6 months of referral.
• Confirmation that the patient does not take a full-strength anticoagulation (blood-thinner) medication and/or any medication that significantly suppresses the immune system on a chronic basis.
• Confirmation that the patient does not have a poorly controlled medical, neurological, or psychiatric condition in addition to AD.
• In addition, the following testing will be necessary to determine eligibility; these can be done either before referral or within the ATP:
  • A test confirming that the patient has elevated brain amyloid, to be completed either prior to referral or after referral. Tests of cerebrospinal fluid (CSF; obtained by lumbar puncture) or amyloid positron emission tomography (PET) imaging may be used for this purpose.
  • A test to determine what versions of the APOE gene the patient carries. This information is needed to understand the risk of side effects.

Lecanemab is given every 2 weeks by a healthcare provider through a needle placed in the patient’s vein (intravenous (IV) infusion) in their arm. Each infusion will last about 1 hour, followed by a period of observation. The MGB ATP will be responsible for providing the patient a schedule of infusions. Infusions will be given at Mass General Brigham hospitals and satellite facilities. At the Brigham, infusions will take place at the Faulkner Hospital or the Main Campus. At Mass General, infusions take place at the Medical Infusion Center.

Lecanemab is currently given every two weeks for a minimum of 18 months. Additional information is being collected on the treatment period to guide decision-making once these 18 months are completed. In addition to infusion visits and regularly scheduled visits with their referring providers, patients receiving lecanemab in the ATP will be seen in the ATP clinic every 6 months (or more often, as indicated) and will have safety MRIs completed after their 4th, 6th and 13th infusion treatments (plus additional MRIs as indicated).

There are several reasons that may lead to stopping lecanemab before the treatment is completed. Examples include severe treatment-related side effects (e.g., swelling and/or bleeding in the brain) or the development of contraindication to treatment, such as being diagnosed with an unstable medical or neurologic condition, needing to start a blood thinner, or progression to moderate stages of dementia. Many other circumstances are possible, and ATP will address them on a case-by-case basis. Patients can always voluntarily stop taking lecanemab at any time during treatment.

Lecanemab can cause small areas of swelling or bleeding in the brain called amyloid related imaging abnormalities (ARIA). ARIA is usually asymptomatic and detected only by monitoring MRI scans. In the phase 3 study investigating lecanemab, only 2.8% of subjects receiving lecanemab had symptoms due to ARIA. Most symptoms were mild, involving temporary symptoms including headache, confusion, dizziness, changes in vision, nausea, or difficulty walking, and were temporary. However, ARIA-related swelling occurred in 12.6% of subjects receiving lecanemab, and 8.4% of subjects had both swelling and bleeding, often without producing symptoms. Patients will therefore need to be monitored with MRIs (usually once per month) until it resolves (usually within 6 months).

Rarely, ARIA can cause seizures or larger areas of inflammation and/or bleeding in the brain. The risks of ARIA, symptomatic ARIA, and serious symptomatic ARIA leading to hospitalization are highest in people carrying 2 copies of the APOE ε4 gene. In the phase 3 study, the rates of symptomatic ARIA with lecanemab treatment were 9.2% in participants with 2 APOE4 genes, 1.7% in participants with 1 APOE4 gene, and 1.4% in participants who did not carry an APOE4 gene. The rates of serious symptomatic ARIA were 2.1% in participants with 2 APOE4 genes, 0.4% in participants with 1 APOE4 gene, and 0.7% in participants who did not carry an APOE4 gene.

ARIA most often occurs within the first 6 months of treatment. We recommend against long distance and/or extended-duration travel during this higher-risk period.

In the first part of the lecanemab phase 3 trial where 1,795 participants received either active drug (lecanemab, 898 participants) or placebo (salt water, 897 participants) over 18 months, there was no difference in the number of participants who died (6 receiving lecanamb and 7 receiving placebo). Following this part, participants were offered to continue in an extension (open label portion) of the study where everybody received active drug (lecanemab) and nobody received placebo (salt water). During this extension, 3 participants (out of about 900) died from side effects thought to be due to lecanemab Two of the deaths were related to brain hemorrhages (bleeding), one occurring in a participant on anticoagulation (a blood thinner), the other in a patient who received tissue plasminogen activator, a medication used to break down blood clots in patients with acute stroke. The third death occurred in a patient homozygous for APOE4 (with 2 copies of the APOE4 gene) who developed swelling and bleeding in the brain similar to a condition involving excessive amyloid protein in blood vessels in the brain with associated inflammation. Under the ATP protocol, patients on anticoagulation will not be eligible to receive lecanemab, and thrombolytic (clot-busting) medications are to be avoided. A key purpose of the screening MRI prior to treatment is to identify findings such as small areas of bleeding (microhemorrhages) and other features suggesting amyloid protein in blood vessels that would lead to a higher risk of serious ARIA. Also, all patients will have APOE genotyping prior to deciding about treatment with lecanemab. This will allow us to identify patients with 2 copies of the APOE4 gene, who are at higher risk for developing side-effects.

Donanemab is another anti-amyloid monoclonal antibody for removal from the brain. It was approved by the FDA on July 2, 2024.

Donanemab is administrated intravenously every 4 weeks for 18 months, although it can be discontinued prior to 18 months once amyloid is successfully cleared from the brain. In a recently published clinical trial, donanemab was shown to reduce the progression of cognitive decline and maintain independence in everyday activities. Click here to review the full results.

The main side effects of donanemab are swelling and bleeding in the brain discovered on a brain MRI, collectively known as amyloid related imaging abnormalities (ARIA). ARIA occurred in 37% of trial participants receiving donanemab, although most ARIA did not cause symptoms. Symptoms due to ARIA developed in 6% of trial participants treated with donanemab. Serious symptoms of ARIA occurred in 1.6% of people on donanemab. ARIA was more common in people with the e4 variant of the APOE gene.

Donanemab joins lecanemab (Leqembi) as the 2nd FDA-approved anti-amyloid antibody treatment approved for Alzheimer disease in the past year. Although the medications have a similar mechanism of action, there are advantages and disadvantages to each.

Aducanumab was studied in two phase 3 studies, that, for various reasons did not provide sufficient data to definitively determine its effectiveness for slowing symptoms of AD. It was granted accelerated approval from the FDA (rather than full approval) and is NOT covered by Medicare.

While the phase 3 study provided a preliminary analysis of selected subgroups of subjects with AD, it was not designed or powered to provide conclusive results about the effectiveness or side effects of lecanemab in these subgroups. Additional data from more subjects will be helpful to answer these important questions. This is one purpose of the registry noted above.

Deciding to start treatment is a decision each patient should make with their care partners and physician. The ATP will continue to be a resource for patients who decide not to receive treatment and will review alternative options such as research and supportive care.

Watch: Hope & Empowerment Through Research

Yes. Prior participation in clinical therapeutic research studies does not make patients ineligible to receive lecanemab, provided the other eligibility criteria are satisfied.

At present, most if not all clinical therapeutic studies investigating potential new treatments for AD do not allow concomitant treatment with lecanemab. This could change in the future. We recommend that patients speak with their current provider and/or contact the Center for Alzheimer Research and Treatment (CART) if there are questions about whether pursuing treatment with lecanemab or enrolling in a clinical therapeutic research study is the best option.

Patients who are currently enrolled in a clinical therapeutic study or an observational study are encouraged to contact their research site about the potential impact of pursuing treatment with lecanemab on their ongoing participation in the study.

• Place an order to the Brigham or Mass General within the patient’s chart in Epic
• For the Brigham, search for Ambulatory Referral to BWH Lecanemab (Leqembi) / Alzheimer Therapeutics Program
• For Mass General, search for Ambulatory Referral to MGH Alzheimer’s Therapeutic Program
• Once in the referral, please attest that the following questions are true:
• You agree to provide longitudinal dementia care (i.e., care outside the use of anti-amyloid treatments).
• If this is not true, please cancel this referral. You can consider referring to the MGH memory disorders unit or the BWH cognitive and behavioral neurology clinic if longitudinal care is needed.
• The patient has objective evidence of cognitive impairment on your assessment.
• Based on your judgement, the early stage of Alzheimer disease is the primary process driving the patient’s symptoms.
• The patient has been informed that Alzheimer disease is their most likely diagnosis.
• The patient is cognitively able to manage all basic activities of daily living (e.g., bathing, toileting, eating) independently.
• The patient is not chronically taking full-strength anticoagulation (e.g., warfarin, apixaban, rivaroxaban, etc).
• The patient does not have a permanent pacemaker.
• The patient is able to undergo and tolerate brain MRI scans.
• The patient does not have any unstable medical (e.g., active malignancy) or psychiatric conditions. Y/N
• Although optional, the referring clinician is asked to consider gathering the following additional data to expedite the evaluation of the patient:
• A basic set of lab tests within the last 6 months: complete blood count, comprehensive metabolic panel, INR, PTT, B12, and TSH.
• Brain MRI within the past 12 months: please perform on a 3T scanner using the ARIA protocol (button located within the MGB Brain MRI order)
• Alzheimer disease biomarkers: amyloid PET or CSF testing
• If you have questions about how to refer, please email bwhATPreferrals@mgb.org.

• Referral Intake Form: The referring clinician needs to fill out the ATP referral intake form and checklist, available here as a PDF.
• Medical Records: Please send copies of all recent office notes, including an updated medication list and past/active medical diagnoses
  • If completed, please send the results of blood tests, brain MRI scans, cognitive screening tests (e.g., MMSE, MOCA, SLUMS, etc), amyloid PET, CSF Alzheimer disease testing, and APOE gene testing.
• Patient Registration: The patient needs to call to register as a patient within the MGB system. The number to call is 866-489-4056. They should have the following information ready when calling to register:
  • Name, Address, Date of Birth, Social Security Number
  • Insurance Information
  • Emergency Contact Information
• MRI Brain: If you have completed a brain MRI, please send us a copy of the images via Powershare (preferred) or mail:
  • Either upload images to Powershare (can contact local radiology team to complete)
  • Or mail a copy of the images on a disc to:
    • ATP Coordinator, Hale Building, 60 Fenwood Rd, Boston, MA, 02114
• Processing: Please fax the completed ATP referral form and relevant medical records to:
  • Fax number: 617-525-0650
  • Please address the correspondence to: Alzheimer Therapeutics Program, new referrals
• Please allow time for referral processing. We will reach out if additional information is required.
• For questions about the referral process, you can email bwhATPreferrals@mgb.org or call 617-525-8780.