The Duke Memory Disorders Clinic in the Department of Neurology will soon offer a recently FDA-approved drug to treat early symptomatic Alzheimer’s disease. Following FDA approval of lecanemab in 2023, donanemab is the second anti-amyloid therapy available to patients. “This new class of drugs is promising. We know that amyloid and tau proteins are a marker of Alzheimer’s disease progression. These drugs encourage the microglia to remove the amyloid from the brain, slowing cognitive decline,” says Kim G. Johnson, MD, Duke geriatric psychiatrist and chief of the Memory Disorders Division in Neurology. 

Donanemab and lecanemab are administered by intravenous (IV) infusion — a new delivery method. Before anti-amyloids, drugs to slow cognitive loss were in pill form, with the last new treatment developed over 20 years ago. “Previous treatments don’t affect disease pathology; they just increase neurotransmitters in the brain. Anti-amyloids are a big deal because they modify the disease,” says Johnson.

Lecanemab and donanemab have many similarities. Most importantly, they are equally effective. “Clinical trials show they slow cognitive loss between 20 and 30% over 18 months of treatment,” says Johnson. 

They are both administered via IV infusions but at different frequencies. Lecanemab is delivered every two weeks, whereas donanemab is administered monthly. 

Both treatments require ongoing MRIs examined by a neuroradiologist to monitor brain changes and detect amyloid-related imaging abnormalities (ARIA). Johnson says, however, that the dosing differs: “Lecanemab is sensitive to weight and dosed 10 mg per kg. Donanemab is a standard dose: 700 mg the first three treatments and then goes up to 1400 mg per treatment.”

To offer donanemab, Duke’s neurology team built upon the novel workflow and guidelines they created for lecanemab in 2023. Duke was one of the first medical centers in the country to offer lecanemab.

Lecanemab and donanemab are for patients diagnosed with mild cognitive loss. “We require a mini cognitive status test to determine a patient’s initial eligibility,” says Johnson. “This is something primary care providers and family practitioners can support with, as patients often report early signs of cognitive loss to them first.”

Research shows that patients get the most impactful results if they start anti-amyloid therapy earlier in the Alzheimer’s disease process, in which amyloid protein increases first, then tau. Patients with mild cognitive impairment when these proteins are just starting to increase benefit most from the drugs.
“The donanemab and lecanemab trials both showed patients with lower tau, indicating earlier-stage disease, had a greater rate of cognitive slowing than those with higher tau,” says Johnson. 

At Duke, patients diagnosed with later-stage or more advanced Alzheimer’s disease are referred to geriatric medicine providers to manage long-term care. Patients with suspected early-stage disease are referred to neurology for extensive evaluation, which includes genetic testing for the APO4 gene, imaging tests such as MRI and amyloid PET, and a spinal tap to determine if amyloid and tau proteins are present in the cerebrospinal fluid. “This testing allows us to confirm the patient’s diagnosis and risk-stratify to determine if anti-amyloid treatment is the best choice for patients,” says Johnson. 

Anti-amyloid therapy is not currently indicated for patients with non-Alzheimer’s disease-related conditions, such as Lewy body, frontotemporal, and Parkinson’s disease dementias.

The most common side effect of IV anti-amyloid therapy is an infusion reaction, which is more common with lecanemab. “26% of patients will develop an infusion reaction after a lecanemab injection, and only 9% after donanemab,” says Johnson. “The good news is that this reaction resolves with time. We also have protocols that help prevent it, like giving an antihistamine before and an antipyretic before the infusion.” 

ARIA is the most serious adverse effect of both treatments. ARIA can emerge as brain swelling, microhemorrhages, or superficial siderosis. Hemorrhages are more common with donanemab in the general population. “Patients who are positive for APOE4 gene — a major genetic risk factor for Alzheimer’s disease — have an even higher risk of ARIA, so donanemab is riskier for these patients,” says Johnson. 

The Duke Memory Disorders Clinic is patient-centric, disclosing all known potential risks of each anti-amyloid treatment. “We are very upfront with patients about their risk profile. It’s our job to educate patients and their families so they can make wise decisions,” says Johnson.