A New Drug Could be Approved for Alzheimer's in June

Background

It has been 115 years since Dr. Alois Alzheimer noted the differences between his patient Auguste D.’s brain tissue and the brain of a healthy person. However, we still do not know the causes nor have we a cure. There have been five drugs for Alzheimer’s that have been approved by the FDA. These drugs are prescribed to treat symptoms of memory, judgment, language, and thinking. Unfortunately, these drugs were only a few points more effective than placebo versions and have serious side effects.

Aducanumab, a new drug currently under review by the FDA, would be the first Alzheimer’s medication to be approved in 18 years (since 2003). Better yet, rather than just treating the symptoms of AD, this drug could change the course of the disease.

Alzheimer’s Disease and Amyloid Plaques

If you were to look at the brain of an Alzheimer’s patient, you would notice many abnormal clumps and bundles comparing that to a healthy brain. The clumps are known as amyloid plaques. They are abnormal clusters of sticky protein fragments that build up between nerve cells and they are thought to lead to brain cell death. The bundles are tau proteins that tangle up in dead or dying nerve cells. While the exact cause of Alzheimer’s is still unknown, scientists suspect that these amyloid plaques have a role in causing Alzheimer’s (this theory is called the amyloid hypothesis).

How does Aducanumab work?

Aducanumab is a monoclonal antibody, a man-made protein that acts as a specific human antibody. It targets amyloid plaques, binds to them, and removes them.

What Symptoms Could it relieve?

While Aducanumab cannot reverse the damage of Alzheimer’s disease, it can slow the progression and some of the symptoms of the disease. Memory loss and general cognition can be reduced with Aducanumab in patients with early symptoms of cognitive decline. The drug can also improve how people with Alzheimer’s engage in daily activities such as going shopping or doing chores, which would allow them to have more independence.

Side Effects?

Around 35% of patients that were given a high dosage of Aducanumab experienced ARIA (amyloid related imaging abnormalities). This is a type of brain swelling that can cause headaches and nausea. People who were APOE-e4 (a gene that increases the risk of Alzheimer’s) carriers had a higher frequency of the ARIA side effect.

Price?

Aducanumab would cost about $ 50,000 a year and would be given as an IV infusion monthly.

Controversy?

In November 2020, Aducanumab’s data was reviewed by the Peripheral and Central Nervous System Drugs Advisory Committee. This committee is the FDA’s outside expert advisory committee. In assessing the evidence of the efficacy of the drug, they overwhelmingly voted no. There were two stage III trials under discussion: ENGAGE and EMERGE. Although the designs of these trials were identical, the results contradicted each other.

In the ENGAGE trial, there was a significant improvement in dementia patients who took the highest dose of Aducanumab. However, in the EMERGE trial, patients who were given the highest dose experienced worse outcomes than the placebo group. Regardless of the advisory committee's consensus, the FDA (Federal Drug Administration) has the final say. Currently, the FDA is reviewing the drug and extended the final decision three months to June 2021. This is because Biogen submitted (per-request of the FDA) more clinical data. The FDA stated that this new data was a “major amendment” and that they would need more time to review.

What to learn more?

https://www.alz.org/national/documents/topicsheet_betaamyloid.pdf

https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2

https://www.biopharmadive.com/news/aducanumab-biogen-alzheimers-drug-ctad-presentation/568583/ https://consultqd.clevelandclinic.org/aducanumab-alzheimers-putting-prime-perspective-video/

http://www.pmlive.com/pharma_news/icer_extends_evaluation_of_biogens_aducanumab_after_fda_delay_1363093

Current Alzheimer's Drugs on the Market

Currently, there are five available drugs for Alzheimer’s. These drugs are made with the purpose to treat symptoms rather than cure the disease.

Donepezil, Galantamine, and rivastigmine are known as cholinesterase inhibitors. This prevents the breakdown of a neurotransmitter called Acetylcholine.

Acetylcholine is a chemical messenger that helps with short-term memory, learning, the formation of memories, and judgment. Acetylcholinesterase is one enzyme that breaks Acetylcholine down and recycles it (after its messages reach the next cell).

In Alzheimer’s disease, cells that produce and use acetylcholine, are damaged and destroyed. So, the cholinesterase inhibitors prevent Acetylcholinesterase from breaking down the acetylcholine so that more acetylcholine remains in the brain.

For those in the mild stages of Alzheimer’s, these drugs can slightly delay the loss of mental abilities. However, these drugs tend to cause many side effects, some of them severe such as insomnia, fainting, nausea, and confusion.

Memantine, a different kind of drug, is used to treat symptoms such as memory, attention, and language in Alzheimer’s patients in the moderate to severe stages. It works by regulating another neurotransmitter called glutamate, which plays a role in learning and memory.

Alexa A Valuable Device for People with Alzheimer's Disease (opinion piece)

My grandmother was diagnosed with Alzheimer’s Disease back in 2015. I have visited her almost every month, and it is difficult to watch her deteriorate from being the most intellectual and outgoing at dinner to barely being able to hold a conversation. She lives in a beautiful old house by herself. Her sense of routine, familiarity, and memory is grounded in that house, where she raised two energetic boys. Over 50 years of her life have been in that house, so it would be very harmful to remove her from that environment now as it would cause immense confusion and possibly lead to depression. It is hard for us to visit her often because she lives a two-hour drive away, so we got a part-time caregiver for her. However, this service is extremely expensive.

If my family’s story at all relates to your family’s, know that we are not alone. The vast majority of people with Alzheimer’s (80%) get care at their homes rather than in nursing homes, as shown by the CDC. This is hard on families as they struggle to provide care for their loved ones with Alzheimer’s: it is very exhausting and takes a lot of time, patience, and money. So, if families can afford it, they hire a caregiver. Unfortunately, caregivers often burn out when working with Alzheimer’s patients. As shown by the Alzheimer’s Association Report, “compared with caregivers of people without dementia, twice as many caregivers of those with dementia indicate substantial emotional and physical difficulties.” This issue in supporting people with Alzheimer’s is becoming more and more of a problem as the prevalence of the disease is skyrocketing. Right now in 2022, around 6.5 million people 65 and up have Alzheimer's Disease in the US. In 2050, this number is projected to be 12.7 million, meaning in a matter of a few decades the prevalence of Alzheimer's Disease is projected to double. We need to find a way to combat this problem that millions of families are having trying to support their loved ones with Alzheimer’s, especially since this issue is only going to grow. I strongly support using Amazon’s Alexa to help fill this support gap because of the help this technology can provide with symptoms of memory loss and agitation along with the cheapness of Alexa compared to full-time care, despite the potential privacy concerns.

Alexa can aid Alzheimer’s patients through reminders, helping with memory, and music, helping with agitation, therefore decreasing the tasks of the caregiver, which can be beneficial for families struggling to care for their loved ones with Alzheimer’s. My family set up Alexa for my grandmother several years ago. For those of you unfamiliar with this technology, Alexa is Amazon’s popular AI device that is activated through voice. Alexa can carry out a large range of tasks, such as saying the weather and sports updates, playing music, and having conversations. One feature that our family has found valuable for our grandmother is setting reminders. The caregiver or one of us sets a reminder with a description of a certain task, for example, “your uber is outside for your physical therapy appointment”. Alexa will simply remind my grandmother out loud when and what she has to do, which avoids worry from our family and caregiver and confusion and frustration from my grandmother. Another Alexa feature that our family has found valuable for my grandmother is its ability to play music. We have created a playlist of songs that my grandmother enjoys listening to, mainly songs from the 40s and 50s. As you probably know, people with Alzheimer’s can sometimes get agitated, and this can be difficult to deal with as a caregiver. When my grandmother gets agitated, our caregiver will ask Alexa to play this playlist, and it helps calm her down a lot. Many people with Alzheimer's respond well to music. The Mayo Clinic reported that it was proven that listening to music can provide emotional benefits for Alzheimer’s patients as well as their caregivers, reducing agitation and stress. For families that are struggling to provide for their loved ones with Alzheimer's, these two features of Alexa, setting reminders and playing music, can be very helpful.

The benefits that this technology provides are complemented by its low price. Alexa can be purchased for $39.99 from Amazon. When compared with the cost of caregivers for Alzheimer’s, this price is an amazing deal, given the benefits it can provide, as mentioned above. According to Seniors Living, the average cost of Alzheimer’s care per month across the states is around $5,000 or $60,000 a year. This is an immense amount of money, considering the fact that the vast majority of families have to pay out of pocket for their Alzheimer’s caregivers as this is not covered by insurance. Getting an Alexa can save a large amount of money for you, just like it has for my family, as this technology decreases the workload and dependence on the caregiver, thus lessening their hours.

Despite the benefits that this technology can provide paired with its low price, concern over privacy often prevents people from testing out Alexa for their family members with Alzheimer’s. This is a viable concern. When my family first purchased an Alexa for my grandmother, we were hesitant as well. In the journal article, “Hey Alexa, is this Skill Safe?: Taking a Closer Look at the Alexa Skill Ecosystem,” Christopher Lentzch, a researcher at Ruhr University Bochum, examined 90,194 Alexa skills for data privacy, and found that around 23% of the Alexa skills had misleading or no privacy policies. That large number is disturbing. Another source of privacy concern over Alexa centers upon the fear of voice recording. Many people fear that Alexa will record conversations and think back to the intrusive telescreens in Orwell’s 1984. While Amazon has assured us that Alexa does not record conversations, it can still be difficult to bring such an advanced AI device into a loved one’s home, which is supposed to be a safe space. If you are worried about privacy, I suggest the caregiver turn off the microphone button when they are not using the device for their Alzheimer’s patient. All this does is that it mutes what is going on so Alexa can not hear anything you say, however, it will still give the Alzheimer’s patient their needed reminders out loud.

Alexa’s reminders and music features can assist families that are struggling to care for their loved one with Alzheimer’s by decreasing the workload as these features help with symptoms of memory loss and agitation. All this comes at a low price. The only hesitancy would come from a privacy concern. I suggest for those of you that are hesitant to purchase an Alexa for a loved one with Alzheimer’s at least try it out. Amazon has a free returns policy for the first 30 days. Set it up in your loved one’s home and see how it works. You never know, it could turn out to be an invaluable device for your loved one with Alzheimer’s, as it did for our family.