Cobbers on the Brain

Memories make up who we are as individuals. When memories are interrupted, degraded, or inhibited, we see cases of dementia such as Alzheimer’s Disease–what we discussed last week. There are many different types of memory that people may form (Fig. 1). Explicit memory refers to memories that individuals can consciously discuss whereas implicit memories cannot be distinctly defined or stated. A type of implicit memory is procedural memory. This type of memory exists for skills and actions–like remembering how to ride a bike or play a sport. Procedural memories may also be referred to as “muscle memory” in popular language. Episodic memory is a type of explicit memory that refers to memories regarding autobiographical events–the who, what, when, where, and why. Semantic memories tend to involve facts and concepts.

This week in class, we discussed traumatic memory in regards to PTSD, Anxiety, Depression, and other psychiatric illnesses. Traumatic memory, also called somatic memory, are strong, resilient memories formed following traumatic, psychologically damaging events. In order for an individual to form a traumatic memory, that same individual has to personally experience the trauma. If a societally traumatic event happens around an individual, a memory formed for that event would be considered a flashbulb memory. As defined in 1977 by Brown and Kulik, flashbulb memories refer to emotionally charged memories formed upon learning about a public emotionally charged or traumatic event. These memories are not autobiographical in nature–they did not occur to the person, but around the person. The name, “flashbulb memories,” stems from their nature of allowing the individual to visualize themselves as they were when the event happened, as if they had taken a picture of themselves during that moment.

Although the nature of the memories may differ, flashbulb memories may be similar to trauma or stress induced memories. Originally, Brown and Kulik, 1977, hypothesized that due to their emotional strength, flashbulb memories might be formed using a unique pathway. The researchers also believed that flashbulb memories were not subject to change–that they were stronger than normal memories and not susceptible to the inevitable forgetting and reforming that other memories experience. More recent research has shown the opposite of Brown and Kulik’s claim regarding the resilience of flashbulb memories. A study by Talarico and Rubin, 2003, used a test-retest methodology to find substantial inconsistencies in flashbulb memory recall–from the initial to the latter recall of the memory.

When it comes to traumatic memories, the study of flashbulb memories has helped researchers understand memories that stem from psychological stress. Specifically, one study looked at the memories made by individuals who were not directly impacted, but lived in New York City during the events occurred on September 11th, 2001. The study assumes that the individuals created flashbulb memories of 9/11 and found, using brain imaging, that their amygdalae still showed increased activity levels three years following the events. These individuals were not at Ground Zero, but lived or worked near the epicenter of the attacks. This finding is important for the distinction between flashbulb memories and traumatic memories. Due to their similar nature, it remains unclear if molecular differences exist between the two types of memory.

When discussing these two types of memory, their similarities seem to outweigh their differences. The major difference between the two seems to be whether the individual themselves experienced the traumatic event or if the individual witnessed the traumatic event as an outside observer. Regardless of this characteristic difference between traumatic memories and flashbulb memories, they likely utilize the same formation pathway (Fig 2). Research understands that once formed, both types of memory may lead to the onset of PTSD, Anxiety, Depression, or other psychiatric illnesses if not properly treated soon after the traumatic event. Although different treatment options exist such as pharmaceuticals like SSRIs, atypical antipsychotics, or mood stabilizers, treatment that utilizes psychotherapy tends to be more successful. Common psychotherapy treatment options include Cognitive Processing Therapy (CPT), Prolonged Exposure (PE), and Eye-Movement Desensitization and Reprocessing (EMDR). Each therapy aims to address and process the negative thoughts one possesses due to the traumatic event. Regardless of the treatment process, it remains important to address negative thoughts–as a result of the trauma–as soon as they appear. The earlier the intervention, the less likely an individual is to develop psychiatric illness following a traumatic event.

The Relationship:

When considering an individual suffering from Alzheimer’s Disease (AD), one doesn’t often associate Type II Diabetes (T2D), or vice versa. However, this may become the new norm as studies are now showing a link between these two diseases. When you take a closer look, many similarities exist, turning this relationship toxic.

What is Alzheimer’s:

Alzheimer’s is a neurodegenerative disorder characterized by progressive mental deterioration due in part to the buildup of amyloid plaques and neurofibrillary tangles in the brain. This type of dementia is the most common worldwide, causing problems with memory, thinking, and behavior. There is no treatment currently capable of reversing, stopping, or significantly slowing down the progression of this disease, making the study of its origination crucial to future treatment.

http://az616578.vo.msecmd.net/files/2016/04/10/635958482997470921934663329_alzheimers1.jpg

What is Type II Diabetes:

Type II Diabetes, or noninsulin-dependent diabetes, is a disease that affects the way that the body metabolizes sugar. This disease is characterized by high blood sugar, insulin resistance, and relative lack of insulin. T2D primarily occurs as a result of obesity and lack of exercise and is seen to be becoming far more prevalent in recent years, likely due the poor diet and lifestyle exhibited by the American society.

The Connection:

Insulin, as we know, plays a large role in the body as a regulator of blood glucose. However, it also has an important role in brain function. Insulin is now understood to play a large part in neuroplasticity, neuromodulation, as well as memory and cognition. Lack of insulin function, as characterized by T2D, can disrupt these pathways, leading to common symptoms seen in Alzheimer’s disease.

Insulin function has been found to be disrupted by prolonged inflammation in the brain as seen in both T2D and AD. In individuals experiencing T2D, the accumulation of fat causes the accumulation of inflammatory molecules. It is likely that obesity associated systemic inflammation causes excesses circulating free fatty acids. These circulating cytokines, free fatty acids, and immune cells reach the brain and initiate local inflammation, including microglial proliferation. This chronic inflammation not only disrupts the insulin pathway in the brain, but also causes synaptic remodeling and degeneration through the overactivation of microglia.

In Alzheimer’s, prolonged inflammation of the brain is a characterizing factor of the disease. This chronic inflammation is largely due to the overactivation of microglia, as seen in T2D. Microglia work to degenerate the buildup of amyloid plaques commonly found in the brain of individuals suffering from Alzheimer’s. When these macrophage-like molecules can’t keep up, they continue to release pro-inflammatory cytokines in response, often damaging neurons and synapses in close proximity. This leads to neurodegeneration. Inflammation itself, such as from T2D, can also trigger the activation of microglia as they both respond to, and cause, neuroinflammation.

Importance:

Though there is no cure for Alzheimer’s, we have found that due to its strong link to T2D, diet may play a role in in alleviating the onset and progression of this neurodegenerative disease. It is important for not only your physical heath, but also future neurological heath, to be cautious of the food you put into your body as it may have a long-term effect.

For those of us who have experienced the terrors of watching a loved one suffer through the horrors of AD, we know the impacts that this knowledge could have. Alzheimer’s is not only detrimental for the individual, but also significantly traumatic for the family as well. Though it is easy to say, “that won’t happen to me” or “I’ll deal with that when I get there”, it may be vastly beneficial to both you and your loved ones to be aware and proactive as it could affect your future and quality of life.

Bibliography:

https://www.sciencedirect.com/science/article/pii/S0889159114000889

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237995/

https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2

https://moodle.cord.edu/pluginfile.php/723477/mod_resource/content/0/2018%20AD%20and%20insulin%20signaling.pdf

Alzheimer‘s disease or AD is a degenerative disease that leads to memory loss, and decline of cognitive functions. Type 2 diabetes (T2D) is caused by problems due to insulin resistance. How are these two different diseases related? Is glucose regulation related to neurons dying? Research has shown that having type 2 diabetes is a major risk factor for AD, and vice verses. These two diseases are more alike than they appear. The inflammation and insulin pathway are two molecular mechanisms that explain the correlation between the two diseases.

 The Insulin Pathway

In order to understand the insulin pathway we must first talk about insulin resistance. This resistance takes place in both AD and type two diabetes.

Type 2 Diabetes: In order to breakdown glucose the body needs insulin. In T2D insulin does not work properly. This leads to high levels of glucose in the body, which causes high blood sugar. Having problems with insulin production can lead to other problems in the body, like in the brain for example.

 Alzheimer’s: Insulin resistance can be shown in postmortem brains of people who suffered from AD. This impaired insulin signaling can be seen clearly in the hippocampus region of the brain. It is thought that insulin resistance in an AD brain may be caused by the build up of amyloid beta plaques. However, this is one hypothesis. There are many more hypotheses being developed surrounding the topic of insulin resistance in the brain.

Inflammation

Insulin resistance plays a large role in the inflammation found in type 2 diabetes, and AD.

Type 2 Diabetes: Obesity, due to poor diet is often linked to the development of insulin resistance, and ultimately T2D. When fat cells accumulate, inflammatory cells follow. One of the main inflammatory cells involved in T2D is the cytokine TNF-α. 

Alzheimer’s: Chronic inflammation is one of the characteristics of AD. The inflammation seen in AD is caused by the immune cell called microglia. The microglia are responsible for the protection and remodeling of synapses in the brain, and help contribute to neuroplasticity. Microglia often produce inflammatory cells in response to increased accumulation of amyloid beta plaques. Research has shown that in order for amyloid beta to cause insulin resistance, and therefore inflammation the cytokine TNF-α must be present.

What does this have to do with my diet?

Our society values convenience, so when given the choice between fast food and taking the extra time to pack food it is not surprising that many of us would choose the fast food option. These poor dietary choices combined with spending your free time watching Netflix can lead to serious problems. Nearly 40% of Americans are obese, and 30% of those who are overweight or obese have type 2 diabetes. While maybe these statistics alone aren’t enough to change your mind maybe this next statistic will make you question whether that extra piece of cake is truly worth it. Having T2D doubles your chances of developing Alzheimer’s Disease. Now I am not saying to ditch fast food entirely, I enjoy treating myself too, but the next time I am given the option of packing my lunch or get fast food, I’ll be packing my own.

 Why should you care?

There is no cure for Alzheimer’s Disease, so it is important to take preventative steps now. Remember, little changes can make all the difference.

• Pack a meal for on the go instead of getting fast food
• Watch TV or Netflix while you work out
• Find health snacks that you enjoy
• Take time for yourself!! Whether it by cooking dinner, or working out try to find healthy practices to implement now. Trust me, your future self will thank you.

Image 1  https://www.psychologytoday.com/us/blog/diagnosis-diet/201609/avoiding-alzheimer-s-disease-could-be-easier-you-think

Source: https://www.ecowatch.com/dr-mark-hyman-why-scientists-now-call-alzheimers-type-3-diabetes-1882174730.html

Alzheimer’s Disease (AD)

Alzheimer’s Disease (AD) is seen throughout popular culture today and is one of the most well known neurodegenerative disease there is. AD is the most common type of dementia, and is what most people often associate the disease with. Symptoms of AD include memory issues, confusion, problems speaking and writing, alterations in mood and personality. Despite how prevalent AD is and how much research is been put behind it, there is still very much that is not known about the progress of AD and why individuals with AD are being affected.

Neurofibrillary tangles

In understanding AD there are several aspects of disease that are essential to bigger picture. Neurofibrillary tangles (NFT) are one of these. In AD one of the major issue that occurs is proteins in the brain called Tau are hyperphosphorylated. This is one of the markers that is used to diagnose AD, as the malformed Tau proteins build up there is so malfunction associated with the cells. Exactly how this happens in not known but scientists are investigating how NFTs are directly associated with AD. It is believed that some or most of the communication between neurons are blocked because of these.

AB plagues

Amyloid is often used to describe proteins that are naturally produced by the body. The specific amyloid that is observed in AD is referred to as beta amyloid (BA) and is built up because the of incorrect cutting on amyloid precursor protein (APP). This incorrect cutting causes there to be longer BA in the brain which accumulates together to form plaques that cannot be broken down.

Figure 1: This image depicts the two most common identifiers of AD in the brain. There is also an observed loss of mass of brain mass, especially in the hippocampus which is an area associated heavily with memory.

Source: http://weeklyhealthtip.blogspot.com/2015/11/the-link-between-type-2-diabetes-and.html

What else do we know?

One of the major players scientists associated with AD are the cytokines of the immune system. Inflammation is seen in individuals who have AD and the response of the immune system to lower this inflammation is to send in cytokines. These are cells that have response on another cell, in this instance to give a response to inflammation. Thinking about the relationship between AD and cytokines is much like pondering the age old question of the chicken and the egg. Increased amounts of cytokines are associated with mutated APP molecules and Tau phosphorylation and eventually leads to neuron death which is a major culprit in neuroinflammation. So was it the inflammation and BA plaques that called the cytokines or excess cytokines that started the inflammation? A bigger question lays behind this, why is there a strong relationship between AD and type 2 diabetes? What about the two strings them together?

Type 2 Diabetes (T2D)

What is it?

Type 2 Diabetes (T2D) which is also known as adult onset diabetes, is when the body no longer processes glucose properly because of insulin resistance or the lack of the production of insulin. Insulin is the molecule in the body that is response for regulating the sugar molecule glucose in and out of the cells. Although T2D is more common in adults, as childhood obesity increases so does the chance of developing the disease. There is no cure for T2D but can be regulated through healthy eating and exercising.  

Figure 2: The connection between the brain and body is undeniable but eating healthy not only helps with the regulation of T2D it also increases the overall sense of wellbeing and may help the brain in the long run, much longer than some people may think.

Source: https://www.medindia.net/patients/lifestyleandwellness/diet-and-alzheimers-disease.htm

Diet and Diabetes

As seen through ways to live with T2D, diet plays a large role. It is important for individuals with T2D to take insulin shots to increase the amount of insulin in the body but in addition to this, as stated above, taking careful notice of the food that you put into your body. As seen with younger individuals, those who experience or are on the verge of obesity are at risk of developing T2D, suggesting there is some relationship between T2D and food associated with obesity. Although the exact reason for T2D diabetes is unknown to researchers there is some evidence to suggest that weight gain and unhealthy eating are apart of the cause. What most people don’t associate with this however, is AD even though there is a clear link between the two.

Figure 3: A venn diagram shows the relationship between T2D and AD by comparing the similarities between the two. As seen above, there are more things in common than many people realize. The major classifiers of AD are seen listed as well but are not observed in T2D.

Source: https://www.mdpi.com/2072-6643/7/9/5341

Insulin in Alzheimer’s Brain: Type 3 Diabetes

Insulin is so well known in the development of T2D, as well as type 1, that many people do not often realize that it plays a major role in other parts of the body, including the brain. Insulin can increase spatial memory, is essential in cognitive and memory functions, as well as influencing feeding behavior. In patients with AD less insulin is seen as well. There is also a correlatory 80% of individuals who have AD also have insulin resistance of T2D, prompting AD to be called type 3 diabetes. Although there is much more research required behind this notion, scientists urge individuals (especially those with T2D or at risk of developing it) to eat better.

Another culprit in the development of both diseases is leptin. Leptin is a hormone that is made by the body to regulate caloric intake and feeding behaviors. In one study in particular, researchers found that there mice with high fat diets did not allow leptin to bind to neurons which never alerted the body that it was full and the mice continued to eat until they were overweight. Leptin also plays a role in the insulin pathway in the brain. Mutated leptin pathways often led to insulin resistance in individuals. This suggests that high fat diets that change the structure and purpose of leptin are not only associated with diseases related directly to insulin, such as T2D, but others like AD that have less information but what is known is the lack of insulin in the brain. This shows that there is no one common link between the three but rather may remain interconnected to each other.

Figure 4: Many individuals with T2D or at least insulin resistance are at risk of developing AD.

Source; https://ediblearia.com/2016/09/11/alzheimers-disease-is-type-3-diabetes/

Many people don’t realize that changing diet now may make a difference later in life. Not only in AD and the progression of the one not only the most debilitating diseases known to man but also the hardest to watch a loved one endure. It is so important for people to understand the connection between these diseases because in doing so it may aid for them to alter their lifestyle now so that they are able to experience the best possible future.

References:  

https://www.alz.org/alzheimers-dementia/10_signs

https://www.brightfocus.org/alzheimers/infographic/amyloid-plaques-and-neurofibrillary-tangles

http://www.diabetes.org/diabetes-basics/type-2/

http://www.mwhomecare.com/diabetes-alzheimers-study/

What is Alzheimer’s Disease? Most likely when you first encountered Alzheimer’s, you heard that it was an individual forgetting things that they had previously known, such as names, events, or even large portions of their lives. The first thought after that is probably: Why? How does this happen in a person’s head? There are two big things that have been found to contribute to Alzheimer’s: neurofibrillary tangles and Aβ plaques.

Neurofibrillary tangles are hyperphosphorylated aggregates of tau protein that come together as insoluble clumps due to problems caused by insulin resistance. These insoluble tangles increase toxicity in the brain and cause neurons in the brain to die. With less neurons in the brain, connections are less easily made and symptoms of Alzheimer’s start to show.

Aβ plaques are collections of amyloid beta peptide oligomers that clump together because of improper cutting of an amyloid precursor protein (APP). This improper cutting is due to a buildup of the GM3 ganglioside. This also causes the insulin receptor to be unable to receive insulin. Then insulin resistance increases.

https://healclinics.com/a-relationship-between-diabetes-and-alzheimers-disease/

Now how does this relate to Type 2 Diabetes? The answer is insulin resistance. Type 2 Diabetes is characterized as your body being unable to use insulin in the correct way. When it can’t be used, it can’t regulate our blood sugar levels causing hyperglycemia, or higher blood sugar levels than normal. We know that insulin is important in maintaining our blood sugar levels; but being a big part of the brain? That is a new idea. Insulin is made in two parts of the body: the pancreas and the brain. It is an important regulator of brain physiology and works as a cognitive enhancer. So if there is resistance to this cognitive enhancer, there will be breakdown in the brain: Alzheimer’s Disease. We see that both the neurofibrillary tangles and Aβ plaques are fundamentally involved in some way, shape, or form with insulin resistance.

http://www.drugood.com/2018/05/30/is-alzheimers-disease-called-type-iii-diabetes/

Now that we have talked a little bit about both Alzheimer’s and Type 2 Diabetes, we can see that there is a connection between the two. That connection being insulin resistance. However, it goes even deeper. Studies show that 70% of all individuals that have Type 2 Diabetes will develop Alzheimer’s Disease at a later time in their lives. That number is staggering to me and it makes me think we need to make some changes at both the individual and societal levels. Individually we need to think about what we eat and get more exercise. Since Type 2 Diabetes is largely characterized by unhealthy eating and lack of exercise, this would be the obvious place to begin. At the societal level, we need to have healthy options available as fast options, not only unhealthy options. Though much of our society is in a “go-go-go” mode, we still need to have a healthy food to fuel us through our days. Though this won’t completely fix the problem, it will likely be worth it to slow down the large numbers that are developing Type 2 Diabetes and in the future Alzheimer’s. I feel that this ‘risk’ of healthy eating and exercise is worth it to remember loved ones and large events that happen in your life.