Alzheimer’s disease (AD) affects over six million people in the U.S. As a nurse, you will likely receive questions from friends and relatives surrounding AD and its potential treatment options. (Lequembi®) is the latest medication approved by the U.S. Food and Drug Administration (FDA) to treat Alzheimer’s.
Alzheimer’s Disease Pathophysiology
First, let’s start with a review of the pathophysiology behind Alzheimer’s. The exact mechanism of AD is unknown, but it prevents cerebral nerve cells from functioning effectively, leading to permanent changes in the brain. Patients with AD appear to have lower levels of choline acetyltransferase resulting in reduced acetylcholine synthesis and impaired cortical cholinergic activity, processes that are important in learning, memory and cognitive function (Press & Buss, 2021). In addition, the development of plaques and tangles within the brain contribute to neuron damage. Plaques are deposits of beta-amyloid proteins that build up in the space between nerve cells, while tangles are twisted fibers of tau proteins that accumulate within cells. These proteins block communication among neurons and play a role in cell damage leading to mental decline. This process naturally occurs in most of us as we age, however in individuals with Alzheimer’s, there’s an increased accumulation of plaques in areas of the brain responsible for memory function.
AD is marked by progressive memory loss and cognitive decline that interferes with activities of daily living. Advanced symptoms include disorientation; mood and behavior changes; confusion surrounding events, time, and place; false suspicious feelings; and difficulty talking, swallowing, and walking (Alzheimer’s Association, n.d.). There is no cure for Alzheimer’s, however advances in research have led to the approval of several medications that have shown to slow the progression of the disease. Cholinesterase inhibitors have been available since the late 1990’s and are often the first-line drugs to treat mild to moderate AD. Three are currently available in the US: galantamine (oral), rivastigmine (oral and transdermal) and donepezil (Aricept®) (oral and transdermal); all work by increasing levels of acetylcholine. Memantine (Namenda®), an N-methyl D-aspartate (NMDA) receptor antagonist, was approved in 2003 to treat symptoms of moderate to severe AD. Both drug classes have shown to produce a small improvement in cognitive abilities, neuropsychiatric symptoms, and activities of daily living (Press & Buss, 2021), however, individual patient responses are highly variable.
NEW! Monoclonal antibodies
Two monoclonal antibodies have been approved by the FDA to slow the progression of AD in patients with mild disease: Aducanumab (Aduhelm®) in 2021 and more recently, lecanemab (Leqembi®) in July, 2023. Both treat and remove specific types of beta amyloid proteins that develop into plaques in the brain but they work differently at distinct stages of plaque formation (Alzheimer’s Association, n.d.). Clinical efficacy data is limited and conflicting among clinical trials for aducanumab. Lecanemab met all primary and secondary efficacy endpoints, meaning it showed meaningful clinical outcomes. For the purposes of this blog, we’ll focus on lecanemab.
Lecanemab (Leqembi®) FAQ
Since lecanemab is new to the market, you are likely to receive many inquiries. Below are some frequently asked questions and simple answers to provide to your patients, family, and friends.
Are all patients with AD candidates for lecanemab?
If in the early stages of AD (mild cognitive function) as assessed by a healthcare provider, lecanemab may be an option. A positron emission tomography (PET) scan or lumbar puncture (spinal tap) will be required to confirm the presence of beta amyloids in the cerebrospinal fluid. In addition, testing for the apolipoprotein E gene variant called APOE4 may be indicated. Approximately 25% of people carry one copy of APOE4, and 2 to 3% carry two copies. APOE4 is the strongest risk factor gene for AD and can lead to severe side effects (Bryan, 2021).
Will lecanemab cure Alzheimer’s disease?
Lecanemab will not cure Alzheimer’s nor will it improve memory or cognitive abilities. In research studies, lecanemab slowed cognitive decline by 27% at 18 months compared to placebo, however it will not completely stop AD from getting worse.
How is lecanemab administered and how long will the patient be on the medication?
Lecanemab is administered by the intravenous (IV) route once every 2 weeks. Treatment will be halted once there is evidence of progression to moderate or severe stages of AD.
Is any additional testing needed?
Magnetic resonance imaging (MRI) of the brain is required prior to starting lecanemab and periodically for the duration of treatment to identify potential side effects.
What are the side effects?
Lecanemab can cause diarrhea and cough. Close monitoring for signs of an infusion reaction such as fever, chills, aches, shaking, joint pain, hyper- or hypotension, headache, changes in eyesight, or allergic reaction is important.
Are there any risks associated with lecanemab?
Lecanemab can cause mild to moderate cerebral edema or bleeding (microhemorrhages) that may resolve on its own or could be life-threatening. These risks are known as amyloid-related imaging abnormalities (ARIA). Irregular gait, dizziness, focal neurologic deficits, headache, nausea, and visual disturbance may result. People taking blood thinners and those with the APOE4 gene (particularly two copies) are at higher risk of these side effects.
How much does it cost?
At the time of this writing, the cost of lecanemab is $26,500 annually. The additional cost of regular clinic visits, periodic MRI and other tests required should also be considered.
Will my insurance cover it?
Private insurance will not cover lecanemab, however Medicare will cover 80 percent of the cost for those who are enrolled in Medicare, diagnosed with mild cognitive impairment or mild Alzheimer’s disease dementia, with documented evidence of beta-amyloid plaque in the brain, and currently being treated by a provider who participates in a qualifying registry with an appropriate clinical team and follow-up care (Centers for Medicare & Medicaid Services [CMS], 2023). A registry is the collection of data about how these drugs work outside of clinical trials.
In conclusion, while these drugs offer a glimmer of hope in the fight against Alzheimer’s, it is important to emphasize that these drugs do not provide a cure. Patients and their families should consult with their healthcare provider to carefully weigh the risks and benefits to determine whether lecanemab or other treatments are clinically appropriate options.
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