Mickie Cathers
When the latest drugs to treat Alzheimer disease are expensive, hard to get, and backed with little evidence, how do pharmacists and other clinicians help patients?
Alzheimer disease affects more than 6.7 million Americans. Due to the nature of this neurodegenerative condition, treating it is much broader than prescribing medications.
“Progression of cognitive impairment starts to go downhill after our mid to late 20s,” said Jeff Sherer, PharmD, MPH, clinical professor at the University of Houston College of Pharmacy. In his talk at APhA2023 in March, Sherer said, “[s]ome people lose some cognitive function but might never hit the level of mild cognitive impairment, which is not dementia. And others might find they’ve progressed through mild cognitive impairment into Alzheimer disease. These designations come into play regarding who gets prescribed medication.”
Current treatment options for Alzheimer disease include pharmacological and nonpharmacological methods.
Pharmacological approaches
There are only a handful of FDA-approved drugs available, including cholinesterase inhibitors (ChEIs), memantine, aducanumab, and lecanemab.
ChEIs—that is, donepezil, rivastigmine, and galantamine—are still first-line treatments for patients as they help with symptoms. They are generally well-tolerated and come in varying dosages. ChEIs have been shown to slow the advancement of symptoms of Alzheimer disease by the equivalent of 6 to 12 months.
ChEIs inhibit acetylcholine turnover and restore synaptic levels of this neurotransmitter. Acetylcholinesterase inhibitors are known for being the most effective, but a patient needs to take the drug four times a day, which isn’t easy for someone struggling with memory issues. They can also adversely affect the liver.
“Alzheimer disease is a progressive condition,” said Sherer. “It’s a win if the patient doesn’t feel different. But how do you explain to a patient that they are 6 to 12 months ‘better’ than where they were predicted to be? People need to understand that you don’t ‘go back to your old self.’ ”
Memantine, an N-methyl-d-aspartate receptor antagonist, is an excitatory that FDA approved in October 2003 for moderate to severe Alzheimer disease. While this drug is well-tolerated by patients and can be used with donepezil, it’s unclear from the data how effective it is.
Changing landscape
In 2018, Pfizer announced it was abandoning research into new drugs aimed at treating Alzheimer disease. “This was a big deal in the Alzheimer disease community and set the stage for the two new amyloid b-directed monoclonal antibodies, aducancumab and lecanemab,” said Sherer.
Aducancumab addresses inflammation and memory loss and is given to patients by I.V. every 4 weeks for the treatment of mild cognitive impairment. Its approval was based on two studies showing a reduction in amyloid b plaque.
However, not only is there insufficient evidence of meaningful clinical benefit for patients, but significant adverse effects, including cerebral edema in 35% of patients and microhemorrhage in 19% of patients, have been reported. MRIs are required at baseline and before the seventh and twelfth doses, per FDA labeling.
Lecanemab is similar to aducanumab. Approved on January 6, 2023, for mild cognitive impairment and mild dementia, and administered by I.V. every 2 weeks, this drug presents insufficient evidence of clinical benefit and significant adverse effects.
Sherer has concerns about the adverse effects, but also about access issues to these drugs.
At this time, Medicare generally only covers both of these drugs as part of a clinical trial, and with the high price tag these newer agents may be out of reach for many patients.
“Since CMS is basically only paying for the newer drugs in the setting of a clinical trial, that’s the only way most patients have even a possibility of accessing them,” said Sherer.
The Alzheimer’s Association has a service named Clinical Trial Match available at: www.alz.org/alzheimers-dementia/research_progress/clinical-trials/trialmatch.
Nonpharmacological approaches
“Nonpharmacologic approaches are way more helpful than the drugs available today,” said Sherer.
Today, many health care providers focus the most on caregiver support for patients with Alzheimer disease and dementia.
These methods might include nonconfrontational redirection, environmental modification (e.g., turning off the gas to the house), and distraction such as giving the patient a way to focus energy on things that won’t harm them.
Written reminders, pet therapy, and reminiscence therapy are also helpful. Short-term memory is what goes first, and so talking with the patient about what they can remember from the past provides comfort as well as going through photo albums together.
Future directions
While research on better drugs, earlier identification, and prevention continue, health care providers can still do a lot to help their patients with Alzheimer disease and their caregivers using both nonpharmacological and pharmacological treatments together.
“Right now, we study patients at the curve from mild cognitive decline into Alzheimer disease, but we should be looking earlier,” said Sherer. “Plaque starts forming in your 40s and 50s. Should we look at that age group? Those are the patients who will clearly benefit. How do you operationalize this? Make them get an MRI once a year? Ask them to start a $56K/day drug now?” ■