- The amyloid protein, which plays a key role in the progression of Alzheimer’s disease, can be found in a variety of forms in the brain.
- Certain subtypes of the amyloid protein have been linked to the development of brain diseases seen in Alzheimer’s disease, according to specialists.
- A new study reveals the discovery of a novel location on a subtype of amyloid protein that could allow antibodies or vaccination to preferentially target this subtype of amyloid protein.
- The ability to target this amyloid-protein subtype selectively may lessen negative effects.
- Researchers used this strategy to develop monoclonal antibodies and vaccine candidates that significantly reduced symptoms in two mouse models of Alzheimer’s disease.
Alzheimer’s disease (AD) is the sixth greatest cause of death in adults in the United States, accounting for 60–70% of all dementia cases.
The disorder is defined by a steady deterioration in cognitive functions such as memory, reasoning, thinking, and language, according to doctors. Except for the controversial medicine aducanumab, which can halt the advancement of the disease, there are no treatments for Alzheimer’s disease, despite the fact that a few drugs can alleviate symptoms.
Scientists have done a significant number of clinical trials in order to develop medications to cure Alzheimer’s disease, but nearly all of them have failed.
Researchers from the University of Leicester in the United Kingdom, the University Medical Center Göttingen in Germany, and Life Arc, a UK medical charity, have now developed two novel candidate immunotherapies that could slow or stop the progression of the disease.
According to the amyloid hypothesis, the amyloid-beta (amyloid- or A) protein has a causative role in Alzheimer’s disease.
Multiple variations of the amyloid protein have been identified by scientists. Certain variations may be more hazardous to brain cells and may play a larger role in the development of Alzheimer’s disease, according to evidence.
“We have identified the form of the amyloid-beta protein responsible for driving AD and have shown that specifically targeting this form of the protein in two mouse models of AD results in substantial improvements in key markers of disease progression,” study co-author Dr. Mark Carr, a professor at the University of Leicester, told Medical News Today.
The researchers created two innovative medicines that target a specific kind of amyloid protein in the current investigation.
TAP01 monoclonal antibodies against this protein could aid in the treatment of Alzheimer’s sufferers. The TAPAS vaccination, on the other hand, would teach the immune system to recognize this protein and help healthy people from developing the disease.
“Both [monoclonal] antibodies and peptide vaccines targeting the type of amyloid-beta found to drive AD progression have been shown in two mouse models of AD to dramatically reduce [or] prevent disease progression.” “The highly favorable benefits shown in mouse models on AD development are significantly greater than any prospective therapeutic antibodies that target amyloid-beta plaques,” Dr. Carr explained.
The findings have been published in the journal Molecular Psychiatry.
The accumulation of the amyloid protein into insoluble aggregates between neurons, known as amyloid plaques, is a characteristic of Alzheimer’s disease.
The amyloid protein’s single units, or monomers, bind together to form oligomers, which are tiny chains of multiple units. These soluble oligomers self-assemble into fibrils, which cluster to form insoluble plaques.
Previously, experts believed that the creation of these amyloid plaques started neurodegenerative processes, resulting in the functional and cognitive impairments associated with Alzheimer’s disease. Drugs that eliminate plaques, on the other hand, have failed to improve the symptoms of the disease in animal models and certain clinical trials.
Instead, studies over the last two decades reveal that amyloid-oligomers are responsible for the amyloid-neurotoxic protein’s effects.
In the brain, there are several types of amyloid protein that vary in length. The full-length forms, A1-42 and A1-40, and the shorter forms, ApE3-42 and A4-42, are the distinct variations of the amyloid protein.
Although A1-42, one of the therapeutic targets for Alzheimer’s disease, can form oligomers, these oligomers assemble quickly to create less toxic plaques.
Shorter or truncated amyloid-protein variations, on the other hand, tend to produce soluble oligomers that last longer.
These truncated amyloid-protein variations are particularly common in the brains of Alzheimer’s patients. Furthermore, the oligomers of these truncated variants are neurotoxic and can disrupt brain cell communication.
Immunotherapies for AD
Antibodies that target amyloid-protein monomers have been created to prevent harmful oligomers from developing, according to experts. However, there are a few flaws in this strategy.
These antibodies also attach to full-length amyloid proteins, which play an important part in normal brain biological processes. As a result, these antibodies are likely to cause negative side effects.
Furthermore, they have the ability to attach to amyloid plaques. One of the first antibodies created to treat Alzheimer’s disease revealed that the antibody’s binding to amyloid plaques was linked to negative effects in some people.
The researchers had previously discovered a mouse antibody that selectively attaches to shortened amyloid proteins but not full-length versions or amyloid plaques, according to the findings.
In the current investigation, the researchers created TAP01 04, an engineered or humanized form of this antibody. Humanized antibodies attach to the same target as mice antibodies but are altered to look like human antibodies.
Humanized antibodies, unlike mice antibodies, do not elicit a robust immune response when given, resulting in less adverse effects. Experts may be able to use the TAP01 04 antibody to help people with Alzheimer’s disease slow down their illness progression.
The researchers also aimed to develop a vaccination that would prevent healthy people from Alzheimer’s disease.
Vaccines teach the body to create an immune response to a disease-causing or pathogen-causing target protein. The goal of this study was to train the immune system to recognize and eliminate shortened amyloid proteins.
The researchers, however, were unable to employ the shortened amyloid proteins for direct vaccination. This was due to the fact that these proteins were not stable in solution and tended to agglomerate.
As a result, the researchers used X-ray crystallography to identify the binding location on the truncated amyloid-proteins that the TAP01 04 antibody recognized.
Although many antibodies can attach to these shortened amyloid proteins, TAP01 04 targeted a specific location. This could explain why TAP01 04 binds to truncated amyloid proteins but not full-length amyloid proteins or plaques, unlike other antibodies.
This information was used to create a stable version of the amyloid-protein fragment. The TAPAS vaccine, a designed protein, shared the TAP01 04 antibody’s binding site with shortened amyloid proteins.
Dr. Thomas Bayer, a professor at University Medical Center Göttingen and a study co-author, said:
“For both drugs, we expect fewer side effects as compared to antibody treatments currently tested in clinical trials or even [the one which has been] approved. Both our vaccine and antibody do not react with Alzheimer’s plaques, which is a great advantage. All other competitor antibodies react with plaques and dissolve the toxic amyloid material after binding, thereby causing side effects.”
“Our drugs detect the soluble precursor amyloid peptide before they aggregate in plaques. In the paper, we describe the discovery of a unique and novel crystal structure, the TAPAS epitope, which is only detected by the vaccine antibody and the TAP01_04 antibody and not by any other comparator antibody. For drug developers, this is important to better understand the binding properties,Dr. Bayer added.
Effectiveness in mouse models of AD
In two animal models of Alzheimer’s disease, the researchers tested the therapeutic effects of the cyclic designer protein (the TAPAS vaccination) and the TAP01 04 antibodies.
The AD mouse model’s brains had lower levels of amyloid plaques after being immunized with either the cyclic designer protein or the humanized TAP01 04 antibody. This demonstrates that, while neither strategy directly targets plaques, both can limit the production of these aggregates by focusing on amyloid monomers.
The researchers then looked at how these immunization techniques affected glucose metabolism in the brain, which is affected by Alzheimer’s disease. In a mouse model of Alzheimer’s disease, both immunization techniques were able to reverse the decline in glucose metabolism.
Memory loss and the death of neurons in certain brain regions, including those involved in memory, are the hallmarks of Alzheimer’s disease, according to specialists.
In a mouse model of Alzheimer’s disease, the researchers discovered that both the TAPAS vaccination and the humanized TAP01 04 antibody enhanced performance in a memory task. Both techniques, at the same time, reduced the loss of neurons in the hippocampus, a brain region that is critical for memory formation.
These findings imply that the TAPAS vaccine and the TAP01 04 antibody were both effective in lowering brain markers linked to Alzheimer’s disease progression.
Clinical trials and their intended applications
Following the success of the two immunization techniques, the researchers plan to undertake more animal investigations and clinical trials.
“Within 3–6 months of finding a good pharmaceutical partner, the humanized TAPAS therapeutic antibodies might be taken into human clinical trials,” Dr. Carr added. Human clinical trials of the TAPAS vaccine are less clear, and would almost certainly require primate safety testing first, but could be doable within two years of finding a commercial partner with vaccine experience.”
“A few more research on which adjuvant works best in humans are needed for the vaccination.” We used a standard mouse adjuvant. “At the time, we don’t know how long the triggered immunological response will last,” Dr. Bayer added.
Dr. Bayer also discussed how the two vaccine techniques will be used to treat Alzheimer’s disease. “The TAP01 04 antibody is ready for clinical trials, has less expected adverse effects, but must be given to patients on a regular basis, such as once a month,” Dr. Bayer added. As a result, like all other antibody medicines, it will be pricey to the health-care system.”
“On the other hand, it will be beneficial to [older] individuals, who frequently have a weak immune system.” TAP01 04 is best used as part of a therapeutic treatment plan once patients have acquired clinical symptoms. We feel it will be beneficial for acute Alzheimer’s treatment rather than long-term use. This translates to “for a shorter period of time.”
“The TAPAS vaccine is ideally suited for use as a preventative treatment method before the onset of Alzheimer’s disease.” Importantly, it is generated at a reduced cost, making it better suited to treating a bigger population,” Dr. Bayer explained.
Dr. Jeffrey Fessel, a professor at the University of California, San Francisco, was also interviewed by Medical News Today. “Clearing cerebral amyloid, even completely, is no guarantee that AD would be reversed. ” noted Dr. Fessel, who was not involved in the study.
“That is for several reasons, chief among which is that AD is multicausal and amyloid is only one of the causes, which implies that the anti-amyloid compound needs support from several other drugs.”
“Another major reason is that the brains of mice differ in several highly important ways from the human brain, e.g., astrocytes comprise 50% of human brain cells, but only 20% of mice brain cells. Those are the two main reasons why pharma has fruitlessly spent billions of dollars, but no anti-amyloid compound has done more than induce minor benefit in AD patients.”
“Unfortunately, the amyloid hypothesis still captivates researchers, most of whom seem to have a narrow-angle field of vision. Another pyroglutamate-modified anti-amyloid-β is welcome but is not game-changing because we already have donanemab, which, given alone, provides minor benefit, but if it were administered with helper drugs, might have a chance at reversing AD, according to Dr. Fessel.
Dr. Fessel emphasized the significance of pursuing prophylactic measures, such as thiamine supplementation, in addition to developing effective techniques for treating AD.
Uses of vitamin B-12 level test: Normal ranges, and results
The amount of vitamin B-12 in the blood or urine is measured in a vitamin B-12 level test to determine the body’s overall vitamin B-12 reserves.
Vitamin B-12 is required for a variety of body functions, including neuron function, DNA and red blood cell formation.
Treatment is required if a person’s vitamin B-12 levels fall outside of the usual range. Vitamin B12 deficiency can cause neurological symptoms as well as fatigue, constipation, and weight loss. B-12 levels that are too high could indicate liver disease, diabetes, or another condition.
Continue reading to learn more about B-12 testing and what the results indicate.
Purpose of a vitamin B-12 level test
The vitamin B-12 level test determines the amount of vitamin B-12 in your body. Doctors can use the data to see if low vitamin B-12 levels are causing symptoms.
If a person exhibits any of the following symptoms, a doctor may recommend a vitamin B-12 level test:
Vitamin B-12 insufficiency
Vitamin B-12 deficiency is thought to affect up to 15% of people in the United States, according to research. The following are signs and symptoms of a deficiency:
- fast heartbeat
- numbness and tingling in the hands and feet
- poor memory
- a sore mouth or tongue
- difficulty maintaining balance
Vitamin B-12 deficiency in infants can cause them to underachieve. They may have mobility issues in addition to developmental delays.
A vitamin B-12 level test may be required for people who have signs of low iron. Pernicious anaemia is caused by a lack of vitamin B-12 absorption, resulting in poor red blood cell causes.
It usually affects the elderly or people who are deficient in intrinsic factor. Intrinsic factor is a gastric material that binds to vitamin B-12 and allows it to be absorbed by the body.
The following are signs and symptoms of pernicious anaemia:
- pale skin
- weight loss
- loss of appetite
High levels of folate in the blood
They can also make you more susceptible to anaemia.
Symptoms of other illnesses
Vitamin B-12 levels that are unusually high can be a symptom of liver disease, diabetes, or certain types of leukaemia. The findings of a vitamin B-12 test may be used by a doctor to help them make a diagnosis.
Vitamin B-12 deficiency is more common in some people than in others, especially those with low stomach acid or other digestive problems. Stomach acid helps the body absorb vitamin B-12 more effectively by separating it from meals.
Low vitamin B-12 levels are more common in the following groups of people than in others:
- people with conditions that reduce vitamin B-12 absorption, including celiac disease and Crohn’s disease
- people who have had gastric bypass surgery
- those who are breast-feeding
- people who are taking medicines such as chloramphenicol, proton pump inhibitors, or H2 blockers
- older adults
- vegans and vegetarians
- people with diabetes
How does the B-12 vitamin level test work?
Vitamin B-12 status is normally determined by a blood test, but home urine tests are now available. Vitamin B-12 levels can be checked as part of a routine blood test by a doctor.
Although fasting is not required before a B-12 test, it may be necessary if the doctor is utilising the test to check at other blood components.
It is important that patients inform their doctors about any medications or supplements they are taking, as some may have an impact on the outcome.
Acknowledging the results
The following are possible results:
- Low. Vitamin B-12 levels below 200 pg/mL are considered low. This indicates that you may have a vitamin B-12 deficiency, pernicious anaemia, or an overactive thyroid. Neurological symptoms are common in people who have low vitamin B-12 levels.
- High. Anything over 900 pg/mL is considered excessively high vitamin B-12 status. This result could indicate problems with the liver or kidneys, diabetes, or certain types of leukaemia.
Because the ranges of results differ from one laboratory to the next, it’s important to talk to a doctor about the results and what they signify.
To rule out vitamin B-12 deficiency, the doctor may measure levels of methylmalonic acid (MMA) and other chemicals. These lab results aid in the early detection of vitamin B-12 deficiency.
Vitamin B-12 deficiency treatment
Vitamin B-12 injections are frequently required by people who have low amounts of the vitamin. These shots are more successful at boosting vitamin B-12 levels than supplements, especially when people have medical issues that make supplements difficult to absorb.
High doses of vitamin B-12 supplements may help some people improve their B-12 status. Supplements are sold in the form of capsules or liquids in pharmacies, supermarkets, health food stores. It may also be beneficial to consume extra vitamin B-12-rich foods.
Treatment for high vitamin B-12 levels
There is no upper limit on vitamin B-12 consumption because high amounts do not cause problems. Having naturally high levels of vitamin B-12 in the body, on the other hand, could be cause for alarm, since it could indicate a serious underlying condition. Doctors will focus on treating the underlying medical condition rather than the vitamin B-12 levels.
Vitamin B-12 foods.
Although low vitamin B-12 levels are frequently caused by absorption problems and other medical conditions, some people may be deficient because they do not acquire enough vitamin B-12 through their food. This is especially true for vegans and vegetarians who have been vegetarian for a long time.
Vitamin B-12-rich foods include:
- fortified plant-based dairy alternatives
- fortified breakfast cereals
- fortified nutritional yeast
- fish and seafood
- dairy products
Vitamin supplements can help vegans and strict vegetarians make up for dietary deficiencies. Older persons should seek to achieve their vitamin B-12 needs through fortified meals and vitamin supplements, as supplements are simpler for their bodies to absorb than naturally occurring vitamin B-12.
Vitamin B-12 dietary recommendations
Vitamin B-12 is required in 2.4 micrograms (mcg) per day for adults and adolescents over the age of 14. During pregnancy, this rises to 2.6 mcg, and breast-feeding raises it to 2.8 mcg.
Vitamin B-12 is an essential nutrient that is necessary for good health. The status of a person’s vitamin B-12 is determined by a vitamin B-12 level test. This test may be recommended by a doctor to people who have symptoms of a deficiency or who are at risk of having low vitamin B-12 levels in their bodies.
Vitamin B-12 deficiency can be avoided by eating a well-balanced diet that includes many sources of the vitamin on a daily basis, or by taking supplements. If they have trouble absorbing vitamin B-12 from food, oral supplements or injections can help them avoid symptoms and consequences.
What are the signs and symptoms of Alzheimer’s disease in its early stages?
Alzheimer’s disease is a type of dementia that affects mostly older people. Alzheimer’s disease strikes people before they reach the age of 65.
Alzheimer’s disease causes memory loss as well as a slew of other symptoms. It is a progressive condition, meaning that the symptoms will worsen over time. The most frequent type of dementia is Alzheimer’s disease.
Experts assume that early-onset Alzheimer’s disease accounts for fewer than 10 percent of all cases. It is usually caused by an inherited genetic trait. It usually appears in people in their 40s or 50s, but it can start as early as their 30s.
Although there is currently no cure, medication can help manage symptoms and slow the condition’s progression.
The symptoms, causes, and treatment options related to early-onset Alzheimer’s disease are discussed in this article.
Providing assistance to a loved one
People can help a loved one with Alzheimer’s disease in a variety of ways. They could, for example, try:
- To gain a better grasp of the person’s situation, learn about Alzheimer’s disease.
- speaking with the individual and partaking in activities that are enjoyable to both parties.
- providing practical assistance, such as food preparation or transportation to appointments
- through support networks, you can connect with other people.
- keeping in mind that this is the same person.
- enquiring about the person’s well-being.
- talking to a counselor or another trustworthy person about your changing relationship is a good idea.
According to Genetics Home Reference, genetic factors are most likely to blame for early onset Alzheimer’s disease.
Some people are born with mutations in specific genes and acquire familial Alzheimer’s disease at a young age. The alterations cause the brain to create harmful proteins, which stack up in the brain and form amyloid plaques, which are clumps of protein.
The genes are passed down through the generations in an autosomal dominant pattern, which means that a person only has to inherit one copy of the mutated gene from a parent to acquire the condition. Frequently, the father suffers from the same condition.
Others don’t have these modifications, and it’s unclear why some people have the condition; nevertheless, additional genes may be implicated.
Symptoms and signs
Memory loss is the most common symptom of Alzheimer’s disease, but other changes can also occur. Other types of dementia can have symptoms that are similar to Alzheimer’s disease, and other illnesses can cause symptoms that are similar to Alzheimer’s disease.
The following are some of the most common signs and symptoms.
1. Impaired daily tasks due to memory loss
Memory loss is frequently the most visible indication of Alzheimer’s disease. A person may begin to forget communications or recent occurrences in ways that are out of character for them. They may ask the same question again, forgetting either the answer or the fact that they asked it previously.
People forget things as they become older, but with early-onset Alzheimer’s disease, this happens earlier in life, more frequently, and appears out of character.
2. Difficulty carrying out routine tasks
It’s possible that the person will struggle to complete a task that they’re used to. For example, they may struggle to:
- prepare a simple meal
- follow the rules of a familiar game
- get to a grocery store, restaurant, or place of employment
As people get older, they may want assistance with new or unfamiliar items, such as the settings on a new phone. This, however, does not always imply a problem.
If, on the other hand, the person has been using the same phone for years and suddenly forgets how to make a phone call, they may be suffering from Alzheimer’s disease-related memory loss.
3. Difficulties with problem-solving or planning
Following directions, solving issues, and concentration may be challenging for the individual. They could find it challenging, for example, to:
- keep track of monthly bills or expenses
- follow directions on a product
- follow a recipe
These issues are common in some people, but if they begin to occur when they did not previously, it could suggest early onset Alzheimer’s disease.
4. Vision and spatial awareness problems
Vision impairments associated with Alzheimer’s disease might cause it difficult for people to assess distances between objects. The person may have difficulty distinguishing contrast and colors, as well as judging speed and distance.
The combination of these eyesight issues can impair a person’s ability to drive.
Because normal aging impairs eyesight, it’s critical to see an eye doctor on a frequent basis.
5. Confusion over time and location
The person may be unsure of where they are or what time it is. Seasons, months, and times of day may be difficult for them to remember.
In a strange environment, they may become perplexed. They may become confused in familiar settings or wonder how they got there as Alzheimer’s disease worsens. They may also begin to wander and become disoriented.
6. Misplacing stuff frequently and being unable to retrace steps
Most people lose things from time to time, but they can generally find them by searching in logical places and retracing their actions.
Someone with Alzheimer’s disease, on the other hand, may forget where they put something, especially if it’s in an unusual location. They may also be unable to track down the missing object by retracing their steps. This might be upsetting and cause to the victim believing that someone is robbing them.
7. Issues with writing or speaking
Words and communication may also be a problem for the individual. They could have trouble following or contributing to a conversation, or they might keep repeating themselves. It’s also possible that the person has trouble writing down their thoughts.
They might come to a halt in the middle of a conversation, unsure of what to say next. They could also have trouble finding the right word or mislabel things.
It is not uncommon for people to have difficulty finding the proper word at times. They usually remember it after a while and don’t have the problem again.
8. Symptoms of reduced judgment
The person’s ability to make sound decisions may have shifted. For instance, they could begin by saying:
- Spending a lot of time on chores that aren’t necessary.
- displaying a lack of interest in personal grooming, including washing
- putting items away in unexpected places, such as placing keys in the refrigerator
9. Mood swings or personality changes
A person with Alzheimer’s disease may notice a change in their mood. They may be irritated, perplexed, worried, or melancholy. They may also lose interest in activities that they previously enjoyed.
They may become annoyed by their symptoms or unable to comprehend the changes that are occurring. Aggression or anger toward others could be a sign of this.
10. Stepping away from social or work activities
As Alzheimer’s disease progresses, a person’s ability to participate in social or work activities may diminish.
|Memory loss||Forgetting things and repeating questions in a way that is unusual||Slowly becoming more forgetful|
|Completing tasks||Difficulty completing familiar tasks such as buying groceries or preparing food||Potentially needing help with new or unfamiliar things such as new technology|
|Problem-solving||Difficulty following instructions such as a new recipe or keeping track of bills||Being a little slower to react to things or juggle multiple tasks|
|Vision||Problems with vision and spatial awareness||Decreasing clarity of vision that may make it harder to distinguish shapes from a distance|
|Timekeeping||Difficulty keeping track of what day it is and becoming confused in an unfamiliar place||Forgetting the reason for entering a room before remembering again|
|Misplacing items||Misplacing items in unusual places and struggling to retrace steps||Momentarily misplacing items before remembering where to find them|
|Communication||Losing track of conversations, repeating sentences, and struggling to write down thoughts||Occasionally struggling to find the right word or needing to concentrate harder to keep up with conversation|
|Decision making||Spending a long time doing unnecessary tasks and neglecting personal grooming||Being a little slower in decision making|
|Mood changes||Experiencing low moods and feelings of irritableness, anxiety, confusion, and depression||Sometimes feeling weary or becoming irritable when there is disruption to a routine|
|Socializing||No longer participating in social activities that previously brought enjoyment||Sometimes feeling tired and worn out by social interactions|
If a person develops one or more of the symptoms listed above, they should see a doctor very away. Early detection may assist to slow the condition’s progression.
Because there is no definite test for Alzheimer’s disease at this time, a doctor will diagnose it based on the symptoms that can be seen. They could try:
- asking certain questions to the person, such as where they live, and evaluating their answers
- conversing with family members to learn about the person’s actions.
- taking into account the individual’s personal and family medical history
- performing various tests to rule out other probable causes, such as blood tests and brain imaging
Because there is presently no cure for Alzheimer’s disease, treatment focuses on symptom management. Among the treatment options available are:
- cognitive stimulation therapy, which may help with memory, speech, and problem solving
- support for living independently
- treatments for insomnia
- behavioral therapy to make life easier for the individual and their loved ones or caregivers
- medications to help with memory loss and possibly slow the progression of the condition
- counseling or medications to help manage depression or anxiety
Better therapy alternatives are constantly being researched.
After being diagnosed with Alzheimer’s disease, most people can expect to survive for another 8–10 years, however the outlook varies from 1–25 years. It will be influenced by the person’s age at the time of diagnosis, with younger people often living longer.
Pneumonia, malnutrition, or body wasting are common causes of mortality.
Alzheimer’s disease has no cure at this time, however medication can help manage the symptoms.
Alzheimer’s disease is more likely to develop as people get older, but people with a family history of the disease may be at a higher risk.
Anyone who feels they or a loved one is suffering from Alzheimer’s disease should consult a physician.
Is there a link between TBI and dementia?
The question of whether traumatic brain injury causes dementia has long been debated, and the results of various research are sometimes contradictory. However, there is increasing evidence that severe brain injury can result in long-term brain damage.
Traumatic brain injuries (TBIs) cause the brain’s normal function to be disrupted. According to the Centers for Disease Control and Prevention, they are caused by a blow or jolt to the skull, or an injury that penetrates it (CDC).
In the United States in 2013, 2.8 million people had a TBI, with around 56,000 of them dying. Small children under the age of four, teens and young adults between the ages of 14 and 25, and people over the age of 75 were the age groups most impacted by TBI. Falls, being struck by an item, and automobile accidents were the most prevalent causes of TBI.
Headaches, blurred vision, slurred speech, and short-term memory impairments are just a few of the early symptoms. TBIs can potentially have long-term health consequences, including an increased risk of seizures and infections.
TBI has been linked to numerous kinds of progressive neurodegeneration, including dementia, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease, according to research, however the evidence is mixed.
Why is it so difficult to come up with irrefutable proof? What are the long-term prospects for TBI victims?
The latest findings
The researchers reviewed medical notes of working-age adults under the age of 65 who had mild or moderate to severe TBI and later got dementia, Parkinson’s disease, or ALS, using the Finnish Care Register for Health Care.
They detected a correlation between moderate to severe TBI and dementia, but no such association was found with Parkinson’s disease or ALS.
Importantly, they discovered that dementia rates in moderate to severe TBI patients were comparable to those in the general population. However, dementia primarily affects the elderly, indicating that TBI raises the risk from old age to working age.
Finland has a tax-funded healthcare system, hence the dataset utilized in this study was extensive. All acute TBI cases are treated in public hospitals, according to the authors, and hence would have been included in the research.
However, data was only accessible for TBI patients who had been hospitalized to the hospital with neurodegenerative symptoms afterward. Other individuals with a diagnosis of neurodegeneration may have been overlooked if they had not been hospitalized at the time, according to the authors.
The findings of the Finnish study matched data published in the Asian Pacific Journal of Public Health last year. Dementia rates were greater among Taiwanese TBI patients than among non-TBI patients in this study.
Another research, just published in the Journal of Alzheimer’s Disease, found no association between TBI and Alzheimer’s disease.
The scientists studied 706 seniors in the United States with and without TBI and discovered that TBI had no effect on cognitive deterioration. However, because TBI was self-reported rather than assessed in the research participants’ medical records, the results may not have been reliable.
The Annals of Physical and Rehabilitation Medicine released a systematic study earlier this year that struggled to identify a relevant link between TBI and Alzheimer’s disease.
Although the evaluation contained 18 trials, the authors were unable to categorize TBI according to severity. It may not have been able to establish a link between TBI and Alzheimer’s disease if mild and moderate to severe TBI were lumped together.
Other disease, on the other hand, has discovered clear correlations between TBI and Alzheimer’s and Parkinson’s disease.
TBI, neurodegeneration link supported
According to a recent study published in the journal The Clinical Neuropsychologist, people with histories of moderate to severe TBI began to experience symptoms and obtained their diagnosis 2.5 years earlier than non-TBI patients in an Alzheimer’s disease patient cohort. However, in this study, TBI was self-reported.
While there was no association between TBI and dementia or Alzheimer’s disease, there was a correlation with Parkinson’s disease, according to a study published in JAMA Neurology last year.
After their deaths, several of the research participants agreed to have their brains autopsied. Both mild and moderate to severe TBI patients displayed evidence of Lewy bodies, a hallmark of Parkinson’s disease, in their brains, as well as signs of cerebral microinfarcts in the moderate to severe TBI patients.
Importantly, while the majority of research participants were 65 and older, a third of mild TBI patients and almost half of moderate to severe TBI patients were 25 or younger at the time of their injury. This shows that TBI may have long-term neurodegenerative consequences.
The difficulty with this sort of study is that it relies heavily on association measurements. This implies that researchers use data to determine whether or if there is a relationship between TBI and neurodegeneration in a certain study group.
However, because cause and effect cannot be shown in these investigations, additional biological pathways may be implicated in producing neurodegeneration in these patients.
Animals are used by researchers to investigate what occurs in the brain after a TBI. The events that followed TBI are starting to be pieced together here.
How can TBI cause neurodegeneration?
A recent paper in Reviews in the Neurosciences detailed what is known about the neurological damage that occurs after a TBI to date.
Blood arteries, neurons, and other cell types are all damaged in the first insult. Neurons get overstimulated as a side consequence, resulting in oxidative stress and cell death. The brain’s water metabolism is also disrupted, resulting in edema.
The blood-brain barrier is compromised, enabling immune cells to invade the injured brain, which is ordinarily resistant to most drugs.
The brain can be permanently harmed by a combination of oxidative damage, neuroinflammation, edema, and poor blood flow.
A recent research published in The Journal of Neuroscience used a mouse model of brain damage to analyze the long-term repercussions of TBI in greater depth.
The areas surrounding the injury site suffered immediate damage. Importantly, persistent neuroinflammation was found to cause long-term damage in distant areas of the brain.
Long-term consequences following TBI were also detected in a mouse model of Alzheimer’s disease, according to a study published in Neuroscience Letters. There were no immediate alterations in the brains of older mice who had received TBI vs those who had not.
For the first week of the trial, both wounded and uninjured mice acquired senile plaques, a characteristic of Alzheimer’s disease. The mice, on the other hand, had much more plaques 28 days after the TBI. There was also a problem with spatial learning.
The researchers deduced that TBI hastens the onset of Alzheimer’s disease symptoms.
What do these findings imply for people who have had a TBI?
The need for long-term monitoring
While it is feasible to examine the cellular processes that occur after TBI in model systems, applying these findings to real patients is more problematic.
Many studies show that TBI has long-term repercussions on the brains of animals and people, but the amount of the damage and its consequences are unknown.
Regardless of their findings, most studies agree that TBI patients, particularly those who have suffered moderate to severe TBI, require long-term monitoring. There is also a request for more precise diagnostic criteria that would allow doctors to detect TBI-related neurodegeneration earlier.
This would allow doctors to keep a close eye on their patients and provide therapies or interventions as soon as possible, therefore delaying the process of cognitive deterioration.
More research is clearly needed, particularly studies that look into cause and effect and can relate the findings to large-scale, reliable demographic data.
It’s also important to keep in mind that not everyone who has had a TBI will develop progressive neurodegeneration.
A total of 1.6 percent of patients with a history of moderate TBI developed dementia in the Finnish research. Even while individuals with moderate to severe TBI were 90 percent more likely to be diagnosed with dementia, the rate was still just 3.5 percent.
While there is solid evidence that a TBI may cause long-term brain damage, concerns remain about why certain patients acquire progressive neurodegeneration and how many people are likely to be impacted.