Traditional Medications for Cognition
In 1907, Dr. Alois Alzheimer published the first case report of a disease which would later bear his name. It wasn’t until 1993 that the first medication, tacrine, would be approved by the FDA to treat this devastating disorder. Although tacrine has been largely discontinued, it has been replaced by other medications which help manage the cognitive symptoms of Alzheimer’s and are collectively known as Cognitive Enhancers. Today, the most commonly prescribed FDA-approved Cognitive Enhancers are Aricept® (donepezil), Exelon® (rivastigmine) and Namenda® (memantine).
Disease Modifying Therapies for Alzheimer’s Disease
The medical treatment of patients with Alzheimer’s Disease has moved beyond modest symptom management to the ability to alter the progression of this disorder through Disease Modifying Therapies (DMTs). Leqembi® (lecanemab, VIDEO) and Kisunla® (donanemab) are FDA-approved monoclonal therapies which treat patients with early-stage Alzheimer’s Disease. Although there are some key differences between these two therapies, both have been demonstrated to remove amyloid protein from the brain and slow disease progression.
The efficacy, or clinical benefit, of Kisunla® and Leqembi® can’t be compared directly because of differences between the studies which formed the basis for approval of these drugs. However, the primary endpoints of the key studies for both demonstrated a slowing of cognitive and functional decline between 25 and 35%. In other words, the average patient treated with either drug might be expected to decline 25 to 35% more gradually than someone who didn’t receive treatment. Of particular interest, however, is that some data suggests that people in whom treatment began especially early might see their cognitive function stabilize or even improve for months or longer. Unfortunately, neither drug is considered to be a cure or able to permanently halt disease progression.
Both Leqembi® and Kisunla® are initially administered as scheduled IV infusions. Leqembi® is initially administered every two weeks. After 18 months of treatment, Leqembi® been approved to convert to monthly infusions or to weekly injections (which can be administered at home). In the case of Kisunla®, there is an approved indication for treatment to be stopped once there is evidence that amyloid has been cleared from the brain. Whether or not to stop or change therapy should be considered on a case-by-case basis after consultation with the treating prescriber.
Both Leqembi® and Kisunla® can cause changes in the brain called ARIA (amyloid-related imaging abnormalities). ARIA is characterized by leakage of blood (ARIA-H) or other fluid (ARIA-E) into or around the brain. ARIA probably occurs because these medications also remove amyloid protein from blood vessels in the brain, causing them to get leaky. ARIA is usually asymptomatic and, if so, is only demonstrated on brain MRI. However, ARIA can sometimes produce symptoms including headache, confusion, and rarely seizures and even death. Although ARIA can occur at any time, it is most likely to occur within the first 6 months of treatment. While all medications in this class of drug can cause ARIA, it is even more likely to occur in patients with certain genetic markers, patients with more advanced dementia, and those who have blood deposition and certain other MRI abnormalities even before treatment is initiated.
For a variety of reasons, most people who are ultimately diagnosed with Alzheimer’s Disease are not going to be appropriate candidates for either of these infusion therapies. Fortunately, additional options are available for patients who can’t receive either of these treatments. Centers around the country are enrolling patients into clinical trials of experimental medications, some of which are given by mouth and may have a better safety profile than that of the current medications. Research centers in Central Texas which are currently enrolling patients with Alzheimer’s Disease into clinical trials include Senior Adults Specialty Research and Central Texas Neurology Consultants.
The future of treatment of patients with Alzheimer’s is bright, although new treatments can’t come soon enough to help all of today’s patients.