Scanning the brain - uncovering the root cause of memory loss and Alzheimer’s disease.

Nobody’s memory is perfect or complete. We jumble things up, we lose track of time. We are in one place, then another and sometimes it can feel like one big inescapable moment. 

Memory problems, however, may be a sign of a more serious diagnosis, such as Alzheimer’s disease. 

Sometimes memory loss starts with simply forgetting what you need to get at the store, then over time you may experience the following: 

• Unable to remember familiar things or people
• Trouble remembering recent events
• Trouble doing familiar things, such as cooking

Research shows up to 20% of those aged 65 and older, already have detectable symptoms of memory loss and mild cognitive impairment (Lopez, 2013). However, diagnosing the cause of memory loss can be very challenging. What if there was a solution for early detection of memory loss? What if we could map your brain to detect conditions such as Alzheimer’s disease, mild cognitive impairment, and other cognitive disorders? 

Evoke Neuroscience has developed an FDA-cleared system called eVox(R). It is an objective test that evaluates cognitive capacity, physiological aging, and brain plasticity. All of these biomarkers can be used to allow for early detection of memory loss. 

Before we get into the article, let’s take a glance at what Alzheimer’s disease is, how it starts, and when to rush to your nearest eVox specialised clinician for your test. 

How Does Alzheimer’s Disease Affect the Brain?

The brain typically shrinks to some degree as a result of healthy aging but, surprisingly, does not lose neurons in large numbers. In Alzheimer’s disease (AD) however, damage is widespread, as many neurons stop functioning, lose connections with other neurons, and die. Alzheimer’s disrupts processes vital to neurons and their networks, including communication, metabolism, and repair.

What Are the Main Characteristics of the Brain with Alzheimer’s?

Amyloid Plaques

Amyloid plaques build up, over time, between nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments that the body produces normally. Beta amyloid is a fragment of a protein snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments would break down and be eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.

 Neurofibrillary Tangles

Neurofibrillary tangles are insoluble twisted fibers found inside the brain's nerve cells. In the case of an Alzheimer’s brain, the molecules of Tau protein disarrange into filaments, which further result in the formation of tangles. As a result, the microtubules fail to remain parallel and straight, and the entire structure collapses. Collapsing of the microtubule structure disrupts the transportation mechanism of the nerve cell, and this results in the degeneration of the cell. 

One important note to consider is, people with Alzheimer's notice symptoms 20-25 years after amyloid plaques and tau neurofibrillary tangles have built up and taken over which makes the eVox test especially exciting!

According to the Alzheimer’s Association, early detection of cognitive impairment offers a wide range of benefits for people with the disease, their caregivers, families and their team of doctors. One major benefit of early detection includes lifestyle interventions. 

Risk factors for developing AD have been identified including health conditions, dietary habits, genetics and heredity, gender, education, age, and lifestyle. Interventions targeted at some of these risk factors may offer opportunities for development of an optimal preventive strategy. Lifestyle habits which include dietary habits and physical activities appear to have a positive effect on modifying many risk factors. 

Now that we understand Alzheimer's disease and we know early detection is the best, let’s have a look at how memory works before we dive into the eVox test: 

 In this article I will discuss 3 things:

1. Memory formation and memory loss
2. What is an EEG and why is it useful?
3. The eVox test - A solution to early detection of cognitive memory impairment

Memory formation and memory loss

The hippocampus is important for memory. It is located in the temporal lobe, which is responsible for receiving auditory information, language, and comprehension. Memory formation involves the strengthening of pre-existing connections, potentiating them so they last long term. This is called long term potentiation, which is important in formation and retrieval of memory (Purves, 2001). An increase in ease in which neurons communicate with each other across synapse causes an increase in excitability. This is the cellular building block of memory formation. 

When people are sleep deprived or stressed, this ability goes straight out the window. 

What happens when stress is involved? 

Short term stress does great things for memory and learning. It increases your heart rate, loosens up blood vessels in the critical area of the brain, delivers more oxygen and glucose to the brain and your brain starts working more efficiently. Stressors make it easier to remember certain things. Neurons become more excitable in the hippocampus and long-term potentiation happens more readily. 

However, during chronic stress, more memory disruption occurs. Once stress goes on for a few hours you are no longer delivering more glucose and oxygen to the brain – you’re delivering less. You are no longer enhancing long-term potentiation, you’re disrupting it, in the hippocampus. With more sustained stress, you change the structure of neurons in the hippocampus and cause them to shrink (Sapolsky, 2018). Chronic stress can potentially worsen neurological outcomes, and further lead to cognitive impairment. 

Now that we understand how memories are formed and lost, how can we enhance the current standard subjective measurements of brain function and activity? 

 What is EEG? 

An EEG, short for electroencephalogram, is a test to evaluate the electrical activity in the brain. Brain cells communicate with each other through electrical impulses. EEG scans are performed by placing small metal discs called EEG electrodes on your scalp. These electrodes pick up and record the electrical activity of your brain. The collected EEG signals are amplified, digitized, and then sent to a computer for storage and data processing. 

 Why is it useful? 

Currently, no cure or drug exists for cognitive impairment. Therefore, detecting cognitive impairment at its early stages is needed for therapeutic treatment to slow or halt progression. Current general techniques such as clinical patient interviewing, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are expensive, not readily available and invasive. The use of EEG for diagnosis has proven potential in identifying the earliest signs of brain dysfunction due to its non-invasive and inexpensive characteristics (Choi, 2019).

In addition, there are several reasons why EEG is an exceptional tool for studying neurocognitive behaviour (Cohen, 2011):

• EEG has very high time resolution and captures cognitive processes in the time frame in which cognition occurs.
• EEG directly measures neural activity.
• EEG is inexpensive, lightweight, and portable.
• EEG monitors cognitive-affective processing in absence of behavioural responses.

The Solution – eVox Test

The eVox test is a portable brain-computer interface that allows doctors to assess the extent and specific locations of cognitive impairment by conducting an EEG test using a 19-sensor electrode cap. It provides a neurocognitive report and brain map of biomarkers that indicate areas of dysfunction. 

The eVox Brain Map can help your doctor develop your optimal treatment plan which can include interventions to fix reversible dementia such as hormonal imbalances and vitamin deficiencies. For example; your doctor might check your thyroid function. Hypothyroidism is one of the most important metabolic causes of reversible cognitive impairment. 

High and high-normal thyroid function is linked to greater risk of developing dementia, but not vascular brain disease, according to research published in Neurology. 

Cardiovascular risk factors are being investigated as a possible modifiable risk factor for dementia, researchers led by Layal Chaker, MD, MSc, of Erasmus University Rotterdam, the Netherlands investigated the role of thyroid function in dementia, cognitive decline, and vascular brain disease.

Another intervention that may be inclusive in a post eVox test plan is a blood test to detect vitamin deficiencies. For example, Vitamin deficiencies have long been known to cause various effects on human health. Vitamin B12 deficiency has been correlated to various neurologic problems; however, research has suggested that abnormally low levels of vitamin B12 can be the cause of significant cognitive dysfunction. Vitamin B12 deficiency is linked to impaired cognition and memory along with a sensation of tingling and numbness, an outcome of poor myelination (Jatoi S, Hafeez D, Riaz S, et al. 2020)

Doctors may use the following biomarkers to recognize early dementia conditions, identify the root causes of memory loss and perform differential diagnosis. 

What are biomarkers? 

A biomarker is an objective measurement of biological processes, used to monitor responses to therapy. E.g. Antibodies are a biomarker of infection. Brain biomarkers that provide insight into how the brain is functioning include: 

• Peak Alpha Frequency (PAF), which reflects cognitive and memory performance. Slow PAF is often seen in patients with Mild Cognitive Impairment and dementia. Fast PAF can be seen in patients with chronic stress, anxiety and insomnia. 
• P300 latency (working memory). According to the results of a controlled trial published in Clinical Electroencephalography, P300 latency accurately predicts memory impairment (Braverman, 2003). Low scores reflect an inability to categorize stimuli, problems with information processing, inattention, lack of focus and cognitive decline. 
• Alpha3/Alpha2 is another brain biomarker that is reflective of long-term memory encoding and information processing. A study showed an increase of Alpha3/Alpha 2 ratio is associated with hippocampal atrophy (Moretti et. Al, 2009)

If the patient has areas that are outside normal limits or that have changed from their baseline, then those are identified in the report. Doctors can then individualize treatment and interventions specifically to those areas. 

 What to expect at your doctor’s visit

The doctor will ask you a lot of question about your memory, including:

• how long you or others have noticed a problem with your memory
• what kinds of things have been difficult to remember
• whether the difficulty came on gradually or suddenly
• whether you’re having trouble doing ordinary things

The doctor also will want to know what medications you’re taking, how you’ve been eating and sleeping, whether you’ve been depressed or stressed lately, and other questions about what’s been happening in your life. If your memory problem needs more evaluation, your doctor may perform the  eVox test to measure brain-based biomarkers that can help them develop an accurate and timely diagnosis.

To find an eVox doctor near you, visit https://evoxbrainmap.com/evox-doctors/

References: 

Al-Qazzaz NK, Ali SH, Ahmad SA, Chellappan K, Islam MS, Escudero J. Role of EEG as biomarker in the early detection and classification of dementia. ScientificWorldJournal. 2014;2014:906038. doi:10.1155/2014/906038

Braverman, E. R., & Blum, K. (2003). P300 (Latency) Event-Related Potential: An Accurate Predictor of Memory Impairment. Clinical Electroencephalography, 34(3), 124–139. https://doi.org/10.1177/155005940303400306

Chaker L, Wolters FJ, Bos D, et al. Thyroid function and the risk of dementia: The Rotterdam Study. Neurology. 2016 Sep 16. doi:10.1212/WNL.0000000000003227 [Epub ahead of print] 

Choi, J., Ku, B., You, Y. G., Jo, M., Kwon, M., Choi, Y., Jung, S., Ryu, S., Park, E., Go, H., Kim, G., Cha, W., & Kim, J. U. (2019). Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals. Scientific reports, 9(1), 10468. https://doi.org/10.1038/s41598-019-46789-2

Jatoi S, Hafeez D, Riaz S, et al. (February 13, 2020) Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia. Cureus 12(2): e6976. DOI 10.7759/cureus.6976 

Lopez OL. Mild cognitive impairment. Continuum (Minneap Minn). 2013;19(2 Dementia):411–424. doi:10.1212/01.CON.0000429175.29601.97

Mistur R, Mosconi L, Santi SD, et al. Current Challenges for the Early Detection of Alzheimer's Disease: Brain Imaging and CSF Studies. J Clin Neurol. 2009;5(4):153–166. doi:10.3988/jcn.2009.5.4.153

Moretti, Davide Vito et al. ‘Increase of Theta/Gamma and Alpha3/Alpha2 Ratio Is Associated with Amygdalo-Hippocampal Complex Atrophy’. 1 Jan. 2009 : 349 – 357.

Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Long-Term Synaptic Potentiation. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10878/

Sapolsky RM. Doubled-Edged Swords in the Biology of Conflict. Front Psychol. 2018;9:2625. Published 2018 Dec 20. doi:10.3389/fpsyg.2018.02625