Alzheimer’s: From a Grandson's Perspective

Author: Eric Kolp, PharmD Candidate
Editor: Brentsen Wolf, PharmD, RUCIF

As I step into the office racked with anxiety, I repeatedly recite my five talking points. I must get this right to have a fighting chance of getting into the school of my dreams. After my bumbling introduction, the interview starts. My grizzled biochemistry professor, the interviewer, divulges the first question “What inspired you to pursue pharmacy?”

This, thankfully, is an easy question for me to answer. My “why” started seven years ago with my grandmother making an offhand comment regarding her burdensome medication regimen. “Why do they have me taking all of these?” she asked, frustrated that she couldn’t quite get that hearty fish oil capsule down. Then and there, I decided that I would learn everything I could about medications and patient care.

My grandmother had early-onset dementia at the time and had quite a few medications, including a number of drugs well known for their risk of side effects like Zoloft (sertraline) and Seroquel (quetiapine). Seeing the way she interacted daily with her medications made me look at how vital they are to a patient’s health regimen. My perspective at the time was that they had a more consistent impact on her life than the doctor visits she had every two months. Pharmacy school gives me a unique opportunity to impact the true day-to-day life of a patient through medications in a way that even physicians can’t always reach.

Dementia is an unusual disease, and even our best medications (including LEQEMBI - recently FDA approved) don't have any “cure” potential. In terms of pharmacotherapy, there aren't many options available. For example, my grandmother was only on two medications throughout her entire disease progression.

Aricept (donepezil), a cholinesterase inhibitor, was her original medication prescribed at diagnosis. Why would a cholinesterase inhibitor be used for dementia? Cholinesterase inhibition is used mainly to offset one of the associated factors with the mental decline seen in dementia. That is, loss of cholinergic neuron production of acetylcholine, resulting in a deficiency seen in patients. Increasing acetylcholine can, in certain patients, decrease symptoms and maintain activities of daily living. It is important to note that donepezil, and other cholinesterase inhibitors, are not able to impact disease progression.

Namenda (memantine), an NMDA receptor antagonist, was only given later as it was FDA approved for moderate to severe Alzheimer’s. The NMDA (N-methyl-D-aspartate) G protein receptor’s main function is to regulate the primary excitatory neurotransmitter in the human brain, glutamate. So, the drug is inhibiting that neurotransmitter to prevent the progression of a disease whose main symptom is mental decline? That makes no sense! The catch: excessive NMDA activity causes excitotoxicity (uncontrolled activation of neuronal amino acid receptors) and promotes cell death. Thus, memantine has efficacy in reducing the overactive NMDA receptors as an uncompetitive, low-affinity antagonist. Unlike cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine), which are strictly for symptomatic relief, there is reason to believe that memantine could potentially be neuroprotective and slow down Alzheimer’s. This was especially true with my grandmother, who started these medications early in the process and was able to decelerate advancement so much that we had a precious extra few years with the woman I loved.

As stated in the previous few paragraphs, there is no cure for this unfortunate illness. Knowing this, it is of the utmost importance for pharmaceutical companies to continue researching and developing molecules so that other families do not have to go through our experience. When a loved one gets diagnosed, the knowledge that we have so few tools can be crushing. I am lucky to have had her for so long, but it does take a toll on caretakers who bear the brunt of the responsibility for care.

Lastly, I want to share an anecdote about my grandmother. Arriving in late June at her “historic” (to me) house on the west side of Indianapolis and seeing her in the hospital bed in a gloomy side room, I knew there wasn’t much time left. Medications had progressed to the point of palliative care, with morphine and diazepam given by syringe at as-needed intervals. Even with the sedating medicines, she was able to crack a smile at seeing my face and raised her hands for a hug. Life doesn’t prepare you for those moments, and it's hard seeing someone who used to be so strong in a moment of weakness. That gesture gave me closure for the most impactful role model of my life.

Through this struggle, my grandmother unknowingly gave me purpose in my career and life. Thank you for reading my story. I hope you gained useful pharmacological knowledge and a unique perspective of chronic disease from an aspiring pharmacy student.

Author Bio:
Eric Kolp is a 3^rd year pharmacy student at Purdue University. He is currently interning in Global Labeling – Oncology at a large pharmaceutical company and will be pursuing a post-doctoral fellowship or full-time position in the pharmaceutical industry. Feel free to reach out to him at ekolp@purdue.edu with any inquiries.

Citations:

1. Wang, Rui, and P Hemachandra Reddy. “Role of Glutamate and NMDA Receptors in Alzheimer's Disease.” Journal of Alzheimer's disease: JAD vol. 57,4 (2017): 1041-1048. doi:10.3233/JAD-160763
2. Kumar A, Gupta V, Sharma S. Donepezil. [Updated 2021 Dec 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513257/