No-Brainer

Have you ever broken glass and tried to glue it back together? It may be the short-term solution but is not a long-term fix. This is similar the current situation with Alzheimer’s disease, there are short term solutions for the broken brain, but no long-term resolutions. Wondering what these short-term solutions may be, continue to follow along as we doctor the disease of Alzheimer’s.

Alzheimer’s is a progressive mental deterioration disease that is characterized by severe memory loss and confusion. Although this disease has been identified since 1906, researchers are still trying to identify the why, what, and how of this disease. The brain of an Alzheimer’s disease patient undergoes an attack causing severe brain deuterations and abnormal protein growth (More information on the Alzheimer’s brain characteristics here). Each day researchers and medical professionals are working towards improving and inventing possible treatments to stop or slow the neurodegeneration caused by this disease. Currently, there’re two main approaches in doctoring the disease, pharmacological treatments, and non-pharmacological treatments.

Pharmacological treatments are amongst the most common method for treating diseases and sickness. Pharmacological is a fancy name for medication/drug treatment. Many different forms of medications have shown promising effects at slowing down the neurodegeneration, but no known drug can cure this disease.  Donepezil is a drug that affects the cellular and molecular process of the neurodegeneration. Donepezil is the most potent drug for mild to moderate Alzheimer’s patients. It works by inhibiting cholinesterase, a chemical neurotransmitter which plays a role in the communication between neurons. The donepezil works by breaking down the acetylcholine allowing for longer neuron to neuron communication. A second drug is donanemab which is a humanized igG1 monoclonal antibody developed from a mouse. This drug has yet to be approved by the FDA, but in research has shown to reduce the amyloid plaques found in Alzheimer’s disease brain (more information on the donanemab advancement can be found here).  A second antibody drug used is aducanumab. Aducanumab is the only-disease-modifying medication currently approved to treat Alzheimer’s. Like donanemab aducanumab works by entering the brain, connecting to amyloid tissue and breaks down the soluble and insoluble amyloid plaque deposits. For individuals who experience mild to moderate Alzheimer’s disease have been given the drug memantine, a NMDA receptor antagonist. Memantine works by blocking the glutamate receptors within the brain.  Excess glutamate causes abnormal brain activity and further accelerates the existing neuronal death.

Overall, each drug shows positive short-term effects on reducing the neurodegeneration of Alzheimer disease, but long-term solutions are still under investigation. Every pharmacological treatment available target different aspect of this disease, but due to the complicated and unknown pathogenesis of Alzheimer’s disease one pharmacological method has not proven to be enough. Researchers are suggesting that a multicomponent drug that targets many aspects of Alzheimer’s pathogenetic features (i.e., targeting amyloid plaques, misfolded tau, and excess glutamate) is needed to have a long-term solution to this disease.

Figure 1: Each pharmacological drug type covered in this blog post and their associated functions in regards to Alzheimer’s Disease.

(Further information on the drug treatments with limited scientific language can be found here)

Associated with all pharmacological treatments are negative side effects. Ever medication used to treat Alzheimer’s disease causes patients to experience symptoms like but not limited to, sleepiness, dizziness, mood swings, nausea, weight loss and confusion. To eliminate these side effects a non-pharmacological treatment would be needed.

Researchers have investigated the idea of non-pharmacological treatments to help slow the progression of this disease, while reducing the negative side effects of medication.  The non-pharmacological treatments include, but are not limited to exercise and motor rehabilitation, cognitive rehabilitation, assistive technology with virtual reality, gaming, and telemedicine. Although research on all treatment methods for Alzheimer’s disease is limited and needs further investigation, each treatment method has shown positive correlations with decreasing the effects of Alzheimer disease, both the behavioural and neurological characteristics. Exercise and motor rehabilitation have had positive correlations with reduced brain atrophy(reduction) in the hippocampus, along with the frontal and temporal regions. Each of these regions are involved heavily in higher cognitive functioning and are at the greatest risk when diagnosed with Alzheimer’s disease. Along with physical rehabilitation cognitive rehabilitation is a robust treatment within Alzheimer’s disease. Cognitive rehabilitation includes cognitive stimulation, cognitive training, and cognitive rehabilitation. Cognitive stimulation works to arouse all cognitive domains while cognitive training focuses on a particular cognitive function. A large limitation with cognitive rehabilitation it shows little to no effect on reducing the neurological deuterations within the patient’s brain. However, this treatment type has shown to improve mood, behaviours, and quality of life which in return decrease caregiver stress. Cognitive rehabilitation is recommended to be paired with another intervention method that has shown positive results in slowing the neurodegeneration. Motor and Cognitive rehabilitation are two of the key types of non-pharmacological treatments available, but there are many other methods under trial. (To review other methods, visit non-pharmacological treatments). Like pharmacological treatments non-pharmacological treatments have shown positive short-term effects on the disease.  Further research into a combined approach is need, it is hypothesized that having both treatment methods would allow for both the neurological (medication) and behavioural (therapy) aspects to be targeted.

Throughout the No-Brainer blog we have covered the neurological and behavioural effects, the risk factors, the advancements within the field and to finish we investigated the methods of doctoring the disease. Although we have not found a cure for the disease, the pharmacological treatments have shown to have positive short-term effects on the diseases neurodegeneration, whereas the non-phrenological treatments have shown to have the greatest effect on decreasing the negative behavioural characteristics associated with Alzheimer’s disease. Alzheimer’s disease research is important as we need to find a cure and not just identify the glue!  

To review the research of each drug in greater detail, click on the drug of your choice: Donepezil, Memantine, Aducanumab

That is all for now!

Alzheimer’s Advancements

Alzheimer’s is a chronic neurodegeneration disease that lacks an available treatment. The neurodegeneration within the brain is caused by an increased presence of amyloid plaques and neurofibril tangles (explained further in last blog post The Villain Brain), which interrupts the functioning of our neurons further leading to neuronal death. As neurons die individuals with Alzheimer’s begin to suffer from significant memory loss and confusion. Still to this day the treatment to stop this disease is missing, but in 2021 a team of researchers completed an experiment investigating a medication treatment to help slow down the neurodegeneration. The treatment used a drug called donanemab, which targets the amyloid plaques found within the brain of a patient with Alzheimer’s disease.

The antibody treatment was given to individuals with early symptomatic Alzheimer’s disease  who shown to have both tau and amyloid build up found by a Positron-emission tomography (PET). A PET is an brain imaging technique that uses radioactive substances to visualize and measure brain activity and structure. After the completion of a PET scan the participants were randomly assigned to receive a dose of donanemab or a placebo, a treatment that has no active ingredients. To measure the effectiveness of donanemab the researchers measured the changes in scores on the Integrated Alzheimer’s Disease Rating Scale, the Clinical Dementia Rating Scale–Sum of Boxes, the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale, the Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Inventory, and the Mini–Mental State Examination, as well as the change to the amyloid and tau clusters based of the PET.

Over the course of the 76 weeks, the donanemab participants showed positive results compared to the placebo group counterparts.  Each measurement system helped demonstrate the effectiveness donanemab had in conjuction with targeting the amyloid plaques. Although this treatment is not yet the cure it is an important advancement with Alzheimer’s research as we are taking steps in the correct direction.  

Check out the articles below for More information!

https://www.nejm.org/doi/full/10.1056/NEJMoa2100708?query=recirc_curatedRelated_article

Mintun M., et al (2021). Donanemab in early alzheimer’s disease. New England Journal of Medicine, 385(7), 666–667. https://doi.org/10.1056/nejmc2109455

Remember a time when you have forgotten about an important; meeting/appointment, conversation, or where you placed an object,  these are daily challenges individuals with Alzheimer's disease encounter. Through the progression of Alzheimer's disease daily tasks like eating and grooming will become difficult, familiar places will become terrible unworked mazes, their loved ones will become strangers. These are just a few of the challenging characteristics associated with Alzheimer’s disease. A big unanswered question is why? Why are individuals facing Alzheimer’s disease?  Let’s find out!

The human brain can be so powerful yet so deadly. Alzheimer’s is a neurodegenerative disease that is not fully understood. Researchers have not nailed down a definite cause or cure, but researchers do know that the brain undergoes a wild attack. With each growing day, 1 in 6 of us are closer to a diagnosis of Alzheimer’s disease. Through years of investigation, researchers have seen protein transformation within the brain that occurs with the onset of Alzheimer’s Disease, but have yet to identify the causes of the protein transformation/accumulation.

It was in 1906, a man named Alois Alzheimer identified strange brain proteins among a group of individuals. The brain proteins were identified as neurotic plaques and neurofibrillary tangles. The plaques and tangles formed similar patterns among a specific group of individuals, who were all experiencing different behavioural characteristics, like memory loss and confusion. This pattern recognition led to a diagnosis of Alzheimer’s disease. The inconsistent proteins formations found within the Alzheimer’s brain is directly connected to the neurons. Neurons are the communication system of our brains, they communicate through electrical impulses and chemical signals. Found within and between the neurons are neurotic plaques and tangles, but the question is how do these formations occur within our brain? Well I blame it on a villain. A villain is a pathogenetic driver that creates an abundance of amyloid plaques and tangles within and around the brain’s communication and nutrient transport system. When the villain begins to invade the healthy brain its first victim is the brain's communication networks. The villain will increase the amyloid β-peptide within the brain. The amyloid β-peptide comes from larger proteins found in the fatty membrane surrounding nerve cells. Amyloid β-peptide begins its peptide journey in the brain as a solitary molecule, in nature, it is chemically “sticky”. The pathogenetic villain allows the sticky peptides to stick together to formulate the amyloid plaques. The amyloid plaques form clusters around and between linking neurons making the communication between each neuron impossible. Communication is interrupted as the plaques will form between the electrical and chemical channels between neurons.

In conjunction with the amyloid β-peptide, the villain also causes a pathogenetic attack by increasing Tau protein within the neuron. Tau protein exists every day within our neuron, it binds to and stabilizes microtubules. Microtubules give internal support and transport nutrients and other essential materials through our neurons.  The pathogenetic villain causes the tau protein to become abnormally hyperphosphorylated and aggregated into bundles of filaments. The hyperphosphorylation causes an abnormal chemical change, signalling for the existing tau protein to detach from the microtubules and join with other tau proteins. When the like proteins (tau-tau) attach within the neuron they create bundles of filaments that eventually take form as neurofibrillary tangles. The Tau connection threads are of neurofibrils in nature and create a tangled mess, similar to unbrushed hair. These massive tangles block the neuron's transport system and weaken the support system. So first the villain attacks our communication and now the nutrient transport system. What will the villain attack next? Thankfully, as far as research shows the pathogenetic villains are done for now, but the effects are long last, meaning the misfolding and tangling continues, blocking more communication and nutrients, further leading to neuronal death.

As neurons die communication between the brains neurons becomes impossible, leading to the many cognitive side effects of Alzheimer’s disease. It has been found that the amyloid plaques drive the neurodegeneration(neuron death) in Alzheimer’s disease. The accumulation of the misfolded Aβ-protein and increased neuron death leads to brain atrophy. Brain atrophy is commonly known as brain shrinkage. The brain area most affected by the atrophy is noted within the medial temporal lobe (side of the brain) more specifically the hippocampus. In a later progression of the disease, brain atrophy can be seen in the cerebrum (cerebral cortex). It stands to reason why Alzheimer's is connected with memory loss as the hippocampus's core responsibility is memory. The chemical change within the tau protein causes a degeneration in learning and memory circuits which are required for cognitive functions.

Figure 1: The left side of the figure represents how a typical healthy brain and neuron appear. The right hand side represents the brain and neuron of an individual with Alzheimer’s disease. Noted in the picture is the relative brain atrophy and increased protein structures associated with Alzheimer’s disease.

To summarize Alzheimer’s disease is not to be taken lightly, the cognitive impairments brought on by this disease cause many challenges for both the individual and their loved ones. The pathogenetic villain creates amyloid plaques to terminate all communication between neurons. Hyperphosphorylation of Tau protein leads to degeneration of the neuronal structure and nutrient transport system. Without proper nutrient flow within the neuron, the neurons begin to die. Neuron death cause wide spread neurodegeneration within the relevant brain structures.

If you or a loved one begins to have large memory lost and/or confusion be sure to visit a doctor to ensure that the pathogenetic villain has not began its invasion within your brain. In the event that villain attacks we must understand ways to stop or slow down these villains. So, stick around the No brainer blog as we will investigate the possible ways to be considered a hero against the pathogenetic villain.

Until Next Time I’m Alaina M.

To read further into the biological changes visit these research articles:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638769/

Alzheimer’s disease, the 6th leading cause of death in the United States. A disease causing many negative side effects to daily life with no known cure.

Research on the experience of receiving and living with a diagnosis of Alzheimer’s is sparse. Existing studies have focused on the initial reactions to the diagnosis, but not the psychological impacts surrounding the diagnosis.

If you or a loved one were experience symptoms of Alzheimer’s disease would you like to receive a diagnosis? The questions of whether, when and how to disclose a diagnosis of Alzheimer’s continues to be debated. Doctors debate the idea of disclosing a diagnosis to their patients with concerns about patients’ welfare and ability to cope.

Are you surprised a doctor could withhold a diagnosis? Any diagnosis can be scary and have a large psychologic impact on individuals, but this article will highlight many positive aspects of receiving/giving a diagnosis. One major reason is it will allow people to adjust to having the disease by employing a range of cognitive and behavioural coping strategies. In my opinion I think disclosing diagnosis is important, I do however think the stigmatism around diagnosis should not exists within society. A diagnosis will allow individuals access to more treatment and therapy. Proper therapy can assist individuals with the psychological impact the diagnosis can have, and allow them access to proper treatments to help slow the cognitive impairments one would experience. After you have read about the benefits of receiving a diagnosis follow up by reading the personal blog in the link below to see how a diagnosis of Alzheimer’s is not the end of the world for a couple. Be prepared that the couple will share details about their experience with Alzheimer’s Disease (the good and the bad).  http://alzheimersocietyblog.ca/the-world-doesnt-end-when-you-have-alzheimers/

I hope to catch you here next time where we will dive into the cognitive impartments and effects of the disease!

Hello Fellow Bloggers!

You are probably wondering why or how you have landed here, but it’s really a No-Brainer. I am Alaina M, a fourth-year science student working towards a major in psychology, a minor in Biology, and a certificate in Applied Behavioural Analysis.

Throughout my degree, I have also had the chance to work in a experimental psychology research lab that focused on cognitive psychology, more specifically language development and reading processes. During this experience, I was able to be a part of the early stages of a new research project. A unique experience I had during my time in the lab was that I received training on how to complete an Electroencephalography (EEG), and had the chance to record brain waves of individuals. After my BSc I hope to pursue an MSc in Science Communications and Disorders and become a Speech-Language Pathologist. Outside of academics, I enjoy reading, baking and going on family vacations (of course before Covid ruined that).

That’s enough about myself, now for the real reason you are here, Science talk. Throughout my time of studying science I have covered a large variety of courses from basic Biology and Chemistry, Biochemistry, Genetics, Immunobiology and Biological Psychology. Through all these courses topics surrounding the brain, diseases, and antibodies have sparked my interest. That is why I have chosen to talk about a disorder that largely effects the brain.  It amazes me how our brains can be so powerful, but also sometimes be our biggest enemy. Throughout this blog, I will be communicating the good, the bad and the ugly about Alzheimer’s disease. A disease that affects 1 in 9 people age 65 and over. A disease with no concrete cause and no cure. Alzheimer’s is a brain disorder, in which the brain slowly destroys its memory and thinking skills, more specifically neurons are injured and die throughout the brain making the communication connections impossible.

Have I lost you yet? I hope not, I understand that research papers can be filled with ridiculous jargon that only the authors understand. This blog intends to communicate scientific research at a new level,  allowing individuals of different backgrounds to understand the message, themes, facts, and research advancement surrounding Alzheimer’s disease.

Can’t wait to catch you next time where we will dive deeper into the brain of Alzheimer’s disease!

--

Alaina M.