Category: Alzheimer’s Disease

Alzheimer’s disease, a type of dementia, is a neurodegenerative health condition which causes memory failure and other brain-related functions, such as speech, behaviour and awareness of surroundings. (Colin L. Masters, 2015) Alzheimer’s disease is a degenerative and progressive disease therefore increasing risk significantly in the older generations and tends to be more prevalent among women. Potential risk factors could include; family history, genetics, head injury, heart-head connection, lifestyle. (ALZ, 2020)

Prevalence/ Mortality/ Incidence

In 2017 Dementia was the second leading cause of death in Australia, with 13,700 deaths and from these deaths 31% were caused by Alzheimer’s disease. (AIHW, 2019) Alzheimer’s is also the most prevalent type of dementia ranging from 50-75% of all cases. (ANU, 2012) The leading cause of death for women in 2017 was also Alzheimer’s disease at 11%, hence, it is certainly not surprising that Alzheimer’s/dementia is on the National Health Priority List in Australia. (AIHW, 2019) In 2018 it was estimated that between 376,000 and 436,000 had dementia. (AIHW, 2019) In 2011 The Australian National University stated that there were approximately 298,000 cases of dementia, they also hypothesised that in 2020 the number of cases would be close to 400,000 cases. (ANU, 2012) This is cause for the government to worry as it seems that in 2018 the number of cases already seems to have surpassed the target number for the year 2020. The incidence rates are only increasing and it’s estimated that by the end of 2058 cases will reach over 1,000,000.

Subgroup – Older Women

Two sub-groups that are more likely to experience Alzheimer’s disease in Australia are older women and Aboriginal and Torres Strait Islander Australians. As seen in figure 1, not only is Dementia and Alzheimer disease the leading cause of death (as said previously) for women, but also the percentage of female deaths is 64.5% and this percentage has not changed since. (Dementia Australia, 2020) Unfortunately, scientists have yet to determine the reason as to why Alzheimer’s, and dementia in general, is more predominant in women. However, according to Alzheimer.net some scientists believe other factors including the hormone change after menopause could be a potential cause but further research must be done to obtain a definitive answer. (Alzheimer.net, 2018) However the outcomes of having the disease can also affect the sexes differently, women tend to feel more guilty but appreciative (Alzheimer.net, 2018). Whereas men, even though less at risk of obtaining the disease, tend to be more aggressive and harder to control when they’re unfamiliar with their surroundings. Only recently a nurse was attacked at Modbury Hospital in Adelaide, South Australia by an elderly man whom had severe Alzheimer’s. (ABC news, 2020) This again shows that more concern should be showed for those suffering with severe cases of Alzheimer’s for both men and women, so medical staff don’t have to deal with such beatings from patients and should therefore maintain its place in the National Health Priority list. Figure 1: Figure 1 shows the leading causes of death in Australia in 2017 between men and women.

Subgroup – Aboriginal and Torres Strait Islander people

The Aboriginal community in Australia has a dementia prevalence of approximately 3 to 5 times more than the non-indigenous Australian population all while also obtaining the disease earlier. Alzheimer’s also being the most prevalent within the Aboriginal community, also, despite such high number’s dementia in these communities is often overlooked by health authorities. The reasons as to why dementia is so prevalent in Aboriginal communities is still being explored, however, dementia has very similar risk factors to many other chronic illnesses which are also predominant are; heart disease, type 2 diabetes, stroke, etc. These risk factors all of which Aboriginal communities prevail in include; obesity, little physical activity, diabetes, poor diet, alcohol consumption, etc. (L Flicker, K Holdsworth, 2014) The amount of people over the age of 55 years is expected to double by 2021 therefore heavily increasing the prevalence of dementia in these communities even further. In the 2008 National Aboriginal and Torres Strait Islander Social Survey it was recorded that over 30% of citizens over 15 years old had problems accessing health care systems. (AIHW, 2011) This is particularly problematic if these groups of people ae to reduce their chances of gaining dementia.

Therefore, Dementia and Alzheimer’s should definitely remain on the National Health Priority list as it is currently the leading cause of death for older women, and extremely prevalent Aboriginal communities. With cases expecting to grow drastically in the near future due to Australia having an ageing population.

Reference list

1. Masters, CL, Bateman, R, Blennow, K, Rowe, CC, Sperling, RA & Cummings, JL 2015, ‘Alzheimer’s disease.’, Nature Reviews., vol. 1.
2. Barnard, ND, Bush, AI, Ceccarelli, A, Cooper, J, de Jager, CA, Erickson, KI, … Squitti, R 2014, ‘Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease.’, Neurobiology of Aging., vol. 35 Suppl 2, pp. S74–S78.
3. Nebel, RA, Aggarwal, NT, Barnes, LL, Gallagher, A, Goldstein, JM, Kantarci, K, … Mielke, MM 2018, ‘Understanding the impact of sex and gender in Alzheimer’s disease: A call to action.’, Alzheimer’s & Dementia : the Journal of the Alzheimer’s Association., vol. 14, no. 9, pp. 1171–1183.
4. Radford, K., Lavrencic, L., Delbaere, K., Draper, B., Cumming, R., Daylight, G., Mack, H., Chalkley, S., Bennett, H., Garvey, G., Hill, T., Lasschuit, D. and Broe, G., 2019. Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians. Journal of Alzheimer’s Disease, 70(s1), pp.S75-S85.
5. Radford, K, Lavrencic, LM, Delbaere, K, Draper, B, Cumming, R, Daylight, G, … Broe, GA 2019, ‘Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians.’, Journal of Alzheimer’s Disease., vol. 70, no. s1, pp. S75–S85.
6. Healthdirect.gov.au. 2020. Dementia Statistics. [online] Available at: https://www.healthdirect.gov.au/dementia-statistics [Accessed 1 April 2020].
7. Aihw.gov.au. 2019. [online] Available at: https://www.aihw.gov.au/getmedia/bfdc9f09-2f31-4ea4-aa31-c20ce76bf828/Dementia-factsheet.pdf.aspx [Accessed 1 April 2020].
8. HealthEngine Blog. 2007. Alzheimer’s Disease (Dementia, Memory Loss) Information | Myvmc. [online] Available at: https://healthengine.com.au/info/alzheimers-disease#What_is [Accessed 1 April 2020].
9. Association, A., 2020. Alzheimer’s & Dementia Help | Australia | Alzheimer’s Association. [online] Alzheimer’s Association. Available at: https://www.alz.org/au/dementia-alzheimers-australia.asp#about [Accessed 1 April 2020].
10. Australian Institute of Health and Welfare. 2019. Deaths In Australia, Leading Causes Of Death – Australian Institute Of Health And Welfare. [online] Available at: https://www.aihw.gov.au/reports/life-expectancy-death/deaths-in-australia/contents/leading-causes-of-death [Accessed 1 April 2020].
11. Anuadri.anu.edu.au. 2013. Types Of Dementia – ANU-ADRI – ANU. [online] Available at: https://anuadri.anu.edu.au/alzheimer-s-disease-facts-figures/types-of-dementia.html [Accessed 1 April 2020].
12. Dementia.org.au. 2020. Dementia Australia | Dementia Statistics. [online] Available at: https://www.dementia.org.au/statistics [Accessed 1 April 2020].
13. ABC News. 2020. Nurse Knocked Unconscious And Needed CPR After Attack By Patient, Union Says. [online] Available at: https://www.abc.net.au/news/2020-02-27/sa-nurse-reportedly-knocked-unconcious-in-modbury-hospital/12006510 [Accessed 1 April 2020].
14. Dementia.org.au. 2014. [online] Available at: https://www.dementia.org.au/files/Alzheimers_Australia_Numbered_Publication_41.pdf [Accessed 1 April 2020].

Abstract

This paper will delve into a few published articles that discuss the various treatments for Alzheimer’s Disease (AD) and the benefits they provide. The articles mention several treatments and assess their effectiveness. Some articles discuss similar treatments, but each article offers an interesting perspective on how effective they can be. The treatments mentioned in the article may not directly treat AD itself, because there is no cure, but can help mediate some of the side effects and accompanying illnesses. This paper examines the known treatment options to help patients with AD cope with the disease and to combat the many side effects that AD brings with it. Most of the information regarding treatments presented in the three articles agree with each other. However, there are slight variations among the articles in how the treatment can be implemented, effectiveness, etc. This paper will analyze those differences and try to understand which of the discussed treatments is most beneficial.

Various Treatments for Alzheimer’s Disease and Their Benefits

Alzheimer’s Disease (AD) is a brain disease that causes memory loss over time, inhibited thinking skills and abilities, and changes and mood or behavior. AD is a serious disease and affects millions of people around the world. Sadly, there is no cure for AD. However, there are a variety of treatment options to help those suffering. It is important to understand how beneficial each treatment may be and if some are more effective than others. This paper examines three different articles that discuss treatment regarding AD. Some articles are more detailed and elaborative about certain treatments than others.

Literature Review

The first treatment option mentioned is improving diet and taking supplements. In Rowland and Davidson’s (2014) article on AD, they mention diet and supplements as a treatment for AD. It is recommended that patients with AD add fish and essential fatty acids to their diet as they have been shown to improve mood and mental function in patients (Rowland and Davidson, 2014). Adding said elements to a diet will not necessarily solve every problem, but it is a nice and easy way to possibly ease some of the side effects. Also, Rowland and Davidson (2014) mention in their article that other supplements can be beneficial. Vitamin E, Thiamine, Cobalamin, and Melatonin are among other supplements that have been found to delay disease progression, improve mental function, improve memory, and reduce sleep disturbances (Rowland and Davidson, 2014, p. 6). Improving diet and taking certain supplements is one way to treat AD and the various problems it causes. However, there are more treatment options available.

Another way to treat the symptoms of AD is medication. This form of treatment is highlighted in Fundukian and Wilson’s article on AD. The medications that are most frequently given to AD patients are Donepezil, Galantamine, and Rivastigmine (Fundukian and Wilson, 2008). These medications benefit the patients by slowing progression of the disease by blocking cholinesterase. It is important to mention that many medications that are recommended for AD cause side effects of their own, which should be factored in when deciding on treatment. Taking medication is a viable treatment option for AD, but there are other treatments that can be pursued to help AD. Gulli and Mallory (2006) also highlight medication of the same goal. In their article, Gulli and Mallory (2006) believe that the best medication for AD are cholinterase inhibitors. This medication stops the process of Acetylcholinesterase within the patient’s body and leads to improved brain function in those in the early stages of the disease (Gulli and Mallory, 2006, p. 70). Since AD causes many other problems in patients -such as depression, delusions, aggression, etc.- there are a plethora of medications that can be taken to reduce various symptoms. Overall, medication as a treatment on its own will only have limited effectiveness, and the same can be said for other treatments as well. However, combine medication with other forms of treatment and the benefits can start to pile up.

To continue, AD can also be treated through different types of therapies. One type of therapy is music therapy. Fundukian and Wilson (2008) say in their article that there are a variety of complementary therapies to treat AD, and music therapy is among them. “Music therapy has been found to calm agitated patients with AD, to improve mood, and to enhance long-term memory” (Fundukian and Wilson, 2008, p. 44). Also, Fundukian and Wilson (2008) say that old songs from the patient’s past that are familiar to them have been found more effective in providing the previously mentioned benefits than any other music. Rowland and Davidson (2014) also talk about music therapy as an option for treatment. A music therapy group is a smart idea to treat AD symptoms and is more beneficial than a verbal group (Rowland and Davidson, 2014). Rowland and Davidson (2014) also mention more advantages of the participation in music therapy. Reduced sleep cycle disturbances, reduced negative perceptions, and an increased awareness of their condition are some of the many potential benefits that music therapy can provide (Rowland and Davidson, 2014).

The known treatment options are certainly important, but the unknown options are just as important. The unknown treatment options refer to treatment that will be much more powerful in combating AD. There are some experimental treatment options that, ideally, will one day lead to a cure. An example of an experimental treatment is gene therapy (Gulli and Mallory, 2006). The idea behind gene therapy is transplanting a gene from a healthy brain and replacing it with a gene in a brain with AD (Gulli and Mallory, 2006). The goal for this specific treatment process is to slow down the process of AD. Gulli and Mallory (2006) said “In April of 2001 the first use of human gene therapy for the treatment of Alzheimer disease was undertaken” (pg.71). However, this particular treatment has since been discontinued due to the adverse side effects on humans (Fundukian and Wilson, 2008). On the bright side, Fundukian and Wilson (2008) say “research on new treatment approaches continues.”

It should be pointed out that two of the sources mention the importance of taking care of the caregivers to a certain degree. The caregivers must not be forgotten when it comes to treating patients of AD. Rowland and Davidson (2014) highlight the challenges that the caregivers face when treating patients with AD. “It is common for caregivers to develop feelings of anger, resentment, guilt, and hopelessness…” (p. 82). Constantly having to care for someone who is likely constantly getting worse is a big burden for caregivers to deal with. To provide for the problems that caregivers might endure, Rowland and Davidson (2014) suggest becoming a part of a support group to help. Gulli and Mallory (2006) also understand that caregivers will need support and relief from constantly caring for AD patients. “Community organizations that offer help should be sought (p. 70).” Caring for the caregivers may be overshadowed when someone is suffering from AD, but it shouldn’t be. The caregiver’s needs are also very important, and there are ways to treat them as well as the AD patient.

Analysis of Credibility (Strengths and Weaknesses)

The credibility of the reviewed sources is overall reliable. Some sources didn’t explore all possible treatment options for AD, which did not limit much. The strengths of the sources lie within the fact that they provided valuable information about the treatment options that were mentioned. The main limitation of the sources is when they were published. All the sources are at least 5 years old, which potentially makes the information outdated. However, the content of the articles is still useful today because most if not all the treatments discussed are relevant to this day. The experimental treatment discussed in the paper is almost two decades old. However, it is the most recent experimental treatment option for AD as there have not been many significant advances of the same caliber since said treatment option. Overall, the sources are very credible and offer a great deal of information on everything AD. The only thing limiting the sources in any way is the date of publication.

Conclusion

Alzheimer’s disease is very complex and dangerous. There is no cure but there are some ways to treat it by reducing side effects and making life easier overall. Patients can add specific nutrients to their diet while taking supplements such as Vitamin E and Thiamine that have been known to ease symptoms. Another treatment possibility is taking medications. Patients can take medication that can block and hinder the process that causes AD to progress. These medications, like dieting and supplementing, can provide many benefits. Some medications are more effective than others, but medication is certainly a feasible treatment option. One more available treatment is music therapy, which is having the patient listen to familiar songs to reduce agitation and improve long-term memory. In conclusion, there are many ways to treat AD, and each are effective in their own way. By using one of the various treatment options, the patient could have a longer life and the time they have left will could be more peaceful and enjoyable. If multiple treatment options were to be implemented at once, the benefits and improvements in the patient are likely to be clearer. Regardless of how many treatments are used, just as little as one can have surprisingly profound benefits for the patient and improve quality of life.

References

1. Alzheimer’s Disease. (2008). In L. J. Fundukian & J. Wilson (Eds.), The Gale Encyclopedia of Mental Health (2nd ed., Vol. 1, pp. 37-45). Detroit, MI: Gale. Retrieved from https://link.galegroup.com/apps/doc/CX2699900022/GVRL?u=fl_sarhs&sid=GVRL&xid=6e86928b
2. Gulli, L. F., & Mallory, N. (2005). Alzheimer Disease. In B. Narins (Ed.), The Gale Encyclopedia of Genetic Disorders (2nd ed., Vol. 1, pp. 67-72). Detroit, MI: Gale. Retrieved from https://link.galegroup.com/apps/doc/CX3451500032/GVRL?u=fl_sarhs&sid=GVRL&xid=664da8c4
3. Rowland, B., & Davidson, T. (2014). Alzheimer’s Disease. In L. J. Fundukian (Ed.), The Gale Encyclopedia of Alternative Medicine (4th ed., Vol. 1, pp. 77-83). Farmington Hills, MI: Gale. Retrieved from://link.galegroup.com/apps/doc/CX3189900034/GVRL?u=fl_sarhs&sid=GVRL&xid=2475a03f

There are many benefits to drinking coffee. According to a new study by the Krembil brain institute, there are many health benefits to having a good morning. In addition to boosting energy and concentration, drinking coffee may help reduce an individual’s risk of developing alzheimer’s and Parkinson’s disease.

After human beings enter the old age stage, there will be a variety of degenerative aging changes, especially in the psychological aspect, such as sensory perception degenerative changes obvious, memory decline, intelligence change, personality change and so on.The most common is alzheimer’s disease, now known as cognitive impairment, a primary degeneration of the central nervous system that cannot be reversed once it has occurred.

Lewy body dementia (DLB) is a group of neurodegenerative diseases whose clinical and pathological manifestations overlap between Parkinson’s disease and Alzheimer’s disease. Most scholars believe that this disease has formed an independent disease, more common in the elderly, male slightly more than female.The etiology and pathogenesis of DLB are unclear.It has been found that DLB and Parkinson’s disease Lewy body are formed by the abnormal aggregation of alpha-synuclein from soluble to insoluble, and the factors affecting the expression and metabolism of alpha-synuclein may be related to the pathogenesis of DLB, which usually has little family genetic tendency. The experiment confirmed that the damage of cholinergic and monoaminergic neurotransmitters in DLB may be related to cognitive impairment and extrapyramidal movement disorder.

EHT is a compound extracted from coffee. Studies have shown that EHT works with caffeine to reduce the incidence of alzheimer’s and Parkinson’s. Alzheimer’s disease (AD) is an insidious and progressive neurodegenerative disease. Clinical manifestations of generalized dementia include memory impairment, aphasia, apraxia, agnosia, impaired visuospatial skills, executive dysfunction, and personality and behavior changes. The disease may be a heterogeneous group of diseases that develop under the influence of multiple factors, including biological and psychosocial factors. According to current studies, there are more than 30 possible factors and hypotheses for the disease, such as family history, female, head trauma, low education level, thyroid disease, high or low childbearing age of the mother, virus infection, etc. Recent statistics show that about 50 million people worldwide suffer from alzheimer’s or other forms of dementia. According to the world health organization, about 60 percent of dementia patients worldwide come from low – and middle-income countries. ‘The total number of dementia cases is expected to reach 82 million by 2030 and 152 million by 2050,’ the who said. As a reference point, the U.S. population is now 329 million.

Caffeine, a xanthine alkaloid compound, is a central nervous stimulant that temporarily dispels drowsiness and restores energy. It is clinically used to treat neurasthenia and coma resuscitation. Caffeinated coffee, tea, soft drinks and energy drinks are so popular that caffeine is the most widely used psychoactive drug in the world. In North America, 90% of adults use caffeine daily. Many natural sources of caffeine also contain a variety of other xanthine alkaloids, including the cardiac drugs theophylline and theobromine, as well as other substances such as tannins. For decades, caffeine has been known to be a powerful stimulant. Its action is especially apparent in central nervous system. Because of the stimulant effect of caffeine and the anxiety it causes in a small number of people, it is often thought that older people and children should consume as little caffeine as possible. But new research suggests that caffeine may be effective in preventing alzheimer’s and Parkinson’s. So, daily coffee consumption or caffeine intake is a good thing for the elderly. Scientists now hope that caffeine and EHT can be combined into a drug to help treat Parkinson’s disease and lewy body dementia (DLB), two incurable conditions.

Studies have shown that coffee can fight Parkinson’s disease and some forms of dementia. Two compounds, including caffeine, work together to prevent the accumulation of toxic proteins in the mice’s brains. The protein, called alpha-synuclein, has been linked to Parkinson’s disease and lewy body dementia (DLB). Tests on rodents genetically at risk for both diseases have shown that the combination of caffeine and compound EHT prevents alpha-synuclein accumulation after just six months. Scientists now hope that caffeine and EHT can be combined into a drug to help treat Parkinson’s disease and lewy body dementia (DLB), both of which have no cure. The study was led by Dr. M Maral Mouradian, a neuroscientist at Rutgers University. According to the figures, nearly one million americans are expected to be diagnosed with Parkinson’s disease by 2020. About 145,500 people have been diagnosed in the UK. PD is a neurodegenerative disease that affects the dopamine-producing brain networks in the substantia nigra. Symptoms include shaking, stiffness, difficulty walking, and a loss of balance and coordination. Lewy body dementia (DLB) is a form of dementia that shares some of the same symptoms as Parkinson’s and alzheimer’s. This happens when alpha-synuclein appears in nerve cells in the brain. The function of alpha-synuclein in healthy brains is unclear. When it clumps, it causes cell death, which is associated with PD and DLB. Treatment for both diseases focuses on reducing the gene expression of the protein and preventing its aggregation. DLB affects about 1.3 million people in the United States, according to the lewy body dementia association. The alzheimer’s association says this is between 10 and 15 per cent of the 850,000 cases of dementia in the UK. Researchers analyzed newborn mice that expressed a gene that causes alpha-synuclein to accumulate in the brain. The rodents were given 50mg/kg of caffeine, 12mg/kg of EHT, or a mixture of the two in their food or water for six months. Tests were then carried out to assess the animals’ ability to move, learn and remember, skills that reflect activity in different parts of the brain. Alone, neither caffeine nor EHT worked. But mice that combined the two compounds had higher test scores. The rodents were then euthanized and their brains examined. This suggests that EHT and caffeine together enhance the activity of the protein PP2A, thereby preventing the accumulation of alpha-synuclein clumps.

Another research shows that when coffee beans are roasted, a chemical called phenyllindane is released, which blocks the release of proteins linked to dementia and Parkinson’s disease.However, phenyllindane does not cure or prevent dementia completely, but it does reduce the risk of dementia.Phenyllindane can inhibit the release of amyloid beta and tau proteins, which are released in tandem between neurons in the brain, and increase the risk of dementia. (glass dish) in vitro tests, the scientists found that two depth after roasting coffee can be particularly effective to prevent protein fragment condensation beta-amyloid and tau protein.The condensation of these brain segments is thought to be a major cause of alzheimer’s and Parkinson’s disease.

In an analysis of all the compounds in the coffee tested, the scientists found that only one, phenyllindane, had an anticlotting effect.And the longer coffee is roasted, the more phenyllindane it contains, so the protective effect is more obvious.Interestingly, both beans showed the same effect when roasted at the same depth, regardless of whether the beans contained caffeine or not, suggesting it was not related to the amount of caffeine.This has helped scientists understand that it is not caffeine but other compounds produced during baking that produce the effect.The substance is the antioxidant phenyllindane, which prevents the formation of so-called amyloid plaques – neurofibrillary tangles that aggravate alzheimer’s disease.

The results suggest that it’s still not clear which compounds in coffee inhibit and prevent alzheimer’s. Because so far, the results from different experiments are not consistent. Overall, there are three conclusions: caffeine has an inhibitory effect on alzheimer’s disease; Caffeine and EHT work together to suppress alzheimer’s disease; And phenyllindane can inhibit alzheimer’s disease. But it’s safe to say that drinking moderate amounts of coffee every day is a healthy lifestyle, as it has been linked to lower rates of alzheimer’s and Parkinson’s disease.

References

1. Kolahdouzan, M, Hamadeh, MJ. ‘ The neuroprotective effects of caffeine in neurodegenerative diseases.” CNS Neurosci Ther 23:4 (2017):272-290.
2. Hussain, A, Tabrez, ES, Mavrych, V, et,al. ‘ Caffeine: A Potential Protective Agent Against Cognitive Decline in Alzheimer’s Disease.” Crit Rev Eukaryot Gene Expr 28:1 (2018):67-72.
3. Nehlig, A. ‘ Effects of coffee/caffeine on brain health and disease: What should I tell my patients?” Pract Neurol 16:2 (2016):89-95.
4. Mancini, RS, Wang, Y, Weaver, DF. “Phenylindanes in Brewed Coffee Inhibit Amyloid-Beta and Tau Aggregation” Frontier in Neuroscience (2018)
5. Rivera, OM, Diaz, RM. “Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review.” Life Science 101:1-2 (2014) 1-9

The most common neurodegenerative disease worldwide is Alzheimer’s and impacts millions of people. This neurodegenerative disease is irreversible and there is currently no known cure: there are only palliative treatments to slow down ever worsening symptoms. The first discovery of Alzheimer’s disease was in 1906 by Dr Alois Alzheimer. It is primarily known for its most obvious symptom of memory loss caused by abnormal changes in the structure of the brain and for this reason is categorised under the broad spectrum of dementia, it accounts for 60-80% of all cases (Kamboh 2018, p133-135). Up to now, research has shown there are three primary risk factors for Alzheimer’s: genetics, age and cardiovascular health.

In Alzheimer’s an abnormal build-up and clumping of proteins called plaques in between neurones severs cell function and this combined with neurofibrillary tangles which disrupt the synaptic communication between neurones. Such physiological alterations, over time, cause changes in behaviour and a decline in the capacity to complete activities of daily life, ADLs (National Institute of aging, 2017). Alzheimer’s typically affects people over the ages of 65 and every five years on from this start point the risk of developing the disease doubles (Alzheimer’s Society 2019). However, there are exceptions. Symptoms of Alzheimer’s can be exhibited in adults as young as 40. This is referred to as early onset Alzheimer’s disease and is thought to be caused by mutations in genes Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) and Amyloid Precursor Protein (APP), in chromosomes 1, 14 and 21 respectively (Bhushan 2018, p3).

Late onset Alzheimer’s disease (AD) can also be caused by genetic alterations and even has a greater risk in terms of polygenetic inheritance because heritability is estimated to be as high as 79% in 95% of late onset Alzheimer’s cases as demonstrated by the research of Gatz M, et al (2006, p133-135). The gene responsible is apolipoprotein E (APOE) which exists as three variants (APOE 2,3 and 4) and found in chromosome 19 (Zhang et al. 2006, p168-174). Each human inherits two of these genes (one from each parent), but is the combination of these which determines the risk of disease. Research suggests there are other genes which are risk factors associated with fat metabolism, inflammation and cellular transport such as MS4A, CD33, PICALM, BIN1, ABCA7, CLU, CR1, EPHA1 and CD2AP. However, the risk is lesser than that of APOE variants. Genetics alone doesn’t cause Alzheimer’s, instead it is a combination of other factors: age and cardiovascular health (Alzheimer’s Society 2019).

Cardiovascular disease (CVD) is the umbrella term for disorders in the heart, circulatory system and blood vessels (Felman 2018). Antecedent risk factors including hypertension (high blood pressure) (Cheng et al. 2011, p424-430) smoking and lipid disorders increase the risk of developing AD (Tosto et al 2016, p1231-1237). CVD has been shown to affect dementia by reducing cerebral blood flow which causes poorer cognitive performance (Bangen et al. year?). Additionally, it is thought to decompose the blood-brain barrier which is important as its purpose is to protect the brain from changes in plasma compositions (Abbott N.J. 2002 p629-638). Interestingly, a study conducted by the Jama Neurology Network suggested that hypertension could possibly protect against AD and lower its risk. However, it could also lead to stroke which in turn increases the risk of AD greatly. This is because stroke is predisposing with a diagnosis of Alzheimer’s if in combination with other CVD diseases.

Symptoms of Alzheimer’s are categorised in stages, ranging from mild to moderate and moderate to severe. The National Institute on Ageing (year?) states that mild symptoms encompass: memory loss, lack of initiative, taking longer to complete ADLs, asking repetitive questions, getting lost and losing personal belongings. They also appear to have an increase in aggressive behaviour and anxiety. It is usually at this stage that the disease is diagnosed. Bature et al. (2017) discovered that in all cases of people with late-onset AD 98.5% suffered from the primary symptoms of depression and 99.1% suffered from cognitive impairment as primary symptoms, respectively. Memory loss typically begins 12 years before official clinical diagnosis and worsens to the extent of losing all motor skills but this is in the very last stage of Alzheimer’s disease.

AD is diagnosed through numerous methods, such as biomarkers, memory tests and changes in behaviour. The disease is generally hard to detect and goes unnoticed in the beginning as behavioural and memory changes are generally unreported and instead concluded as being coincidence. In addition, it cannot be definitely identified by one singular physical scan, or examination. In fact, for a definite diagnosis, autopsy confirmation is required which means the patient has already become deceased (Shaw et al. 2009, p403-413). The current methods of identification are cerebrospinal biomarkers, such as; phospho-tau, total-tau and beta amyloid in the 42 amino acid form. These differentiate and determine different neurological diseases. Another diagnostic is the use of vector machines to differentiate AD from frontal-temporal lobar degeneration and normal aging which has a 95% accuracy level (Brain, 2008 p2969-2974).

The cure for Alzheimer’s disease is currently non-existent. Instead current medical research just allow for the management of the disease to maintain the well-being and functionality of the patient as an individual for as long as possible. Such medications include cholinesterase inhibitors and memantine which help to recuperate memory and attentiveness. Alternatively, natural treatments would include making modifications to diet and lifestyle to reduce cardiovascular risks and in turn reduce Alzheimer risks: Weller and Budson (2018) found that it is possible to prevent overall cognitive atrophy by just improving the patient’s lifestyle. In fact, this is the first thing diagnosed patients are recommended to change regardless of their stage in AD (Weller J. and Budson A. 2018).

The cholinesterase inhibitors utilized are donepezil, rivastigmine and galantamine which act to decrease the chemical breakdown of acetylcholine which is a chemical responsible for the transmission of signals between nerve cells. However, nerve cells are progressively lost from the use of acetylcholine because it breaks down in the brain. A decrease in acetylcholine and the worsening of AD symptoms are inextricably linked. The drugs mentioned above are called inhibitors because they inhibit the enzyme acetylcholinesterase which decomposes acetylcholine in the brain. Consequently, the transient increase of acetylcholine in the brain results in better communication between nerve cells which temporarily alleviate symptoms. On average the palliative treatment is effective for 6 to 12 months. Unfortunately, after this period, symptoms slowly worsen. The benefits of the drug outweigh the inevitable damage which proceeds it. However, there are contradictory thoughts about these drugs even though most people benefit from improved ability to complete ADLs, motivation, memory, concentration and reduced anxiety (Alzheimer’s Society 2014). Memantine is another drug used to treat AD, although unlike the other drug treatments it is usually administered to patients in the moderate to severe symptom category because of evidence suggesting it can help decrease delusions, agitation and aggression as recommended by The NICE guidance (2011). Memantine functions by blocking the brain from exposure of excess glutamate, a chemical which in excess causes damage to brain cells but otherwise transduces signals to and from nerve cells). Unfortunately, glutamate is released excessively after brain cells are damaged by AD creating a cycle of damage (Alzheimer’s Society 2014).

The research can suggest that the battle against Alzheimer’s disease is far from over. Drugs without side effects and with higher effectiveness need to be created. Presumably, the next steps to tackling the disease involves a method to detect the beginning of the formation of tau tangles and tangles in the neurofibrils, after all it is these factors which are the start point of a plethora of symptoms: the aftermath being possible incontinence and the inability to walk, move and talk. Additionally, other drugs need to be developed because the inhibitors only provide temporary relief. AD is primarily associated with age. But questions still remain: why do humans begin a process of degeneration? why are human bodies susceptible to degenerative changes when aged over 65 years? Perhaps looking at Alzheimer’s from a different angle will lead to results and hopefully one day a real cure.

Bibliography

1. Abbott N.J. (2002), Astrocyte-endothelial interactions and blood-brain barrier permeability. Journal of Anatomy, 200 (6), pp.629-638.
2. Alzheimer’s Society n.d. Available at: https://www.alzheimers.org.uk/about-dementia/types-dementia/alzheimers-disease [Accessed:]
3. Bangen K.J, Nation D.A, Clark L.R, Harmell A.L, Wierenga C.E, Dev S.I, Delano-Wood L, Zlatar ZZ, Salmon D.P, Liu T.T, Bondi M.W. (2014), Interactive effects of vascular risk burden and advanced age on cerebral blood flow, Frontiers in Aging Neuroscience, 7(6), pp.159.
4. Bature F, Guinn B, Pang D, Pappas Y (2017), Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016, BMJ Open, 7(8).
5. Bhushan I, Kour M, Kour G, Gupta S, Sharma S, Yada A (2018), Alzheimer’s disease: causes and treatments- a review, Annals of Biotechnology, 1(1), pp.1-8.
6. Blennow K, (2004), Cerebrospinal fluid protein biomarkers for Alzheimer’s disease, NeuroRX, 1(2), pp.213-225.
7. Drug Treatments for Alzheimer’s Disease, Available at: https://www.alzheimers.org.uk/sites/default/files/pdf/factsheet_drug_treatments_for_alzheimers_disease.pdf [Date Accessed:]
8. Felman (2018), Medical News Today: Everything you need to know about heart disease. Available at: https://www.medicalnewstoday.com/articles/237191.php [Accessed:]
9. Gatz M, Reynolds C.A, Fratigliioni L, Johansson B, Mortimer J.A, Berg S, Fiske A, Pedersen N.L (2006), Role of genetics and environments for explaining Alzheimer’s disease, Arch Gen Psychiatry, 63(2), pp.168-174.
10. Geriatr J, Bekris L.M, Yu C.E.Y, Bird T.D, Tsuang D.W (2010), Genetics of Alzheimer’s disease, Journal of Geriatric Psychiatry and Neurology, 23(4), pp.213-227.
11. Kamboh I. (2018), A brief synopsis on the genetics of Alzheimer’s disease, Current Genetic Medicine Reports, 6(4), pp. 133-135.
12. Kloppel S, Stonnington C.M, Barnes J, Chen F, Chu C, Good C.D, Mader I, Mitchell L.A, Patel A.C, Roberts C.C, Fox N.C, Jack C.R, Ashburner J, Frackowjak R.S.J (2008), Accuracy of dementia diagnosis- a direct comparison between radiologists and a computerised method, Brain, 131(11), pp.2969-2974.
13. National Institute on aging, (2017), Available at: https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease [Date Accessed:]
14. Shaw L.M, Vanderstichele H, Knapik-Czajka M, Clark C.M, Aisen P.S, Petersen R.C, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee V.M.Y, Trojanowski J.Q (2009), Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects, Annals of Neurology, 65(4), pp.403-413.
15. Tosto G, Bird T.D, Bennett D.A et al (2016), The role of cardiovascular risk factors and stroke in familial Alzheimer’s disease, Jama Neurol, 73(10), pp.1231-1237.
16. Weller J, Budson A, (2018), Current understanding of Alzheimer’s disease diagnosis and treatment, F1000 Research, 7.
17. Xu J, Patassini S, Rustogi N, Riba-Garcia I, Hale D.B, Phillips A.M, Waldvogel H, Haines R, Bradbury P, Stevens A, Faull R.L.M, Dowsey A.W, Cooper G.J.S, Unwin R.D (2019), Regional protein expression in human Alzheimer’s brain correlates with disease severity, Communications Biology, 2
18. Zhang W, Luo T, Qiu S, Ye J, Cai D, He X, Wang J (2018), Identifying genetic risk factors for Alzheimer’s disease via shared tree-guided feature learning across multiple tasks, IEEE Transactions on Knowledge and Data Engineering, 30(11), pp.2145-2156.

INTRODUCTION

Alzheimer’s disease (AD) was first diagnosed by Dr. Alois Alzheimer in 1906, it has become the most prevalent neurodegenerative disease overall. Alzheimer’s disease (AD) is clinically defined as the appearance of progressive deficits in cognition and memory. The two types of AD are Familial AD (FAD) and Sporadic AD (SAD). Both have the clinical and pathological similarities, exhibiting progressive cognitive dementia, senile plaques consisting of amyloid β (Aβ) peptide and neurofibrillary tangles (NFTs) consisting of phosphorylated tau protein. Axonal transport defects, synapse loss and selective neuronal death are others cellular phenotypes shared by FAD and SAD.FAD is early-onset which accounts for 5% of cases and is caused by highly penetrant and rare autosomal mutations of the PS1, PS2 and, less frequently, amyloid precursor protein (APP) genes. APP protein is fundamental for central nervous system (CNS) function acting in the formation of synapses, neurogenesis, axonal transport, signalling and plasticity. SAD is late-onset that has established risk factors beyond age including cardiovascular disease, low education, depression, and the apolipoprotein-E4 (ApoE4) gene. There are no clear dominant or recessive SAD mutations; however, many genetic variants have been identified and there is clearly a strong heritable component to the disorder. Thus, SAD has multifactorial origins, driven in part by a complex genetic profile and in part by environmental factors and the interaction of the two. AD reaches the central nervous system (CNS) it is difficult to obtain samples of the patient’s nervous tissue before his death to study the disease. It is possible, using the relatively recent technique called induced pluripotent stem cells (iPSCs),which allows to reprogram the patient’s somatic cells to a pluripotent state by the forced expression of a defined set of transcription factors.

INDUCED PLURIPOTENT STEM CELLS

After the discovery of the iPSCs in 2006 by Yamanaka and colleagues, it became possible to reprogram the patient’s somatic cells back to a pluripotent state, forcing the expression of a defined set of transcription factors. The induced pluripotent stem cells showed similar colony morphology, gene expression, cell surface marker expression, and the ability to self-renew. For this reprogramming, four transcription factors (OCT4, SOX2, KLF4, and c-MYC) need to be introduced into fibroblasts through retroviruses. The cells acquire a pluripotent stage with characteristics extremely similar to the embryonic stem cells. The first transfection was performed on mouse fibroblasts, followed by transfection into human fibroblasts. Considering the difficulty with AD, the discovery of iPSCs shows a great potential and advantage to enable the modelling of in vitro diseases. Parkinson’s disease, amyotrophic lateral sclerosis, smooth muscle atrophy, and family dysautonomia were the diseases initially studied using the iPSCs approach to model neurological diseases. These are monogenic disorders or versions of complex diseases caused by known mutations.

IMPORTANT ADVANCES IN ALZHEIMER’S DISEASE USING iPSCs

Using iPSCs allowing a better understanding of cellular and molecular target. One of the studies involving iPSCs generated for AD were carried out in 2011 by Yahata et al., and Yaqi et al. Yahata et al., successfully generated forebrain neurons from human iPSCs cells, and showed that Aβ production in neuronal cells was detectable and inhibited by some typical secretase inhibitors and modulators. According to the authors, hiPSCs cell-derived neuronal cells express functional β- and γ-secretases involved in Aβ production. Anti-Aβ drug screening using these hiPS cell-derived neuronal cells requires sufficient neuronal differentiation. Also, Yaqi et al. generated iPSCs from fibroblasts of FAD patients with mutations in PS1 and PS2 and characterized the differentiation of these cells into neurons. They demonstrated that patient-derived differentiated neurons have increased Ab42 secretion, recapitulating the pathological mechanism of FAD with PS1 and PS2 mutations. These two studies represent, thus, critical first steps in assessing the potential of AD iPSCs to model AD. iPSCs is a pre-clinical tool for screening therapeutic compounds. The approach is central to toxicity and efficacy testing, in the new drug development landscape and the precise engineering of the genome and transcriptional and proteomic analysis.

FUTURE CONCERN

With the advance of research using the iPSCs, the customization of the treatment for patients with AD is possible, reaching new insights associated with the pathogenesis and discovery of new drugs for the treatment. At present, we can model in vitro diseases to allow patient-specific therapies from newly derived AD-iPSCs to be used by considering the appropriate characterization of AD patient groups through genetic profiles and biomarkers. In iPSCs, we can highlight the level of maturity of the neurons, lack of efficient protocols to generate microglia, and few protocols of 3D differentiation that appropriately mimic the in vivo environment of the brain . To generate and differente iPSCs are still a time-consuming and expensive processes. iPSCs can be used from an individual to direct their appropriate treatment through personalized medicine, improving the patient’s life. During the formation of iPSCs, there are a concern about introducing harmful mutations. Therefore, new genome editing techniques, such as the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) nuclease system, reduce the risk of introduction and spread of undesired mutations.

APPLICATION OF iPSC IN ALZHEIMER’S DISEASE

In light of the important benefits conferred by their self-renewal and multidirectional differentiation capacity, iPSCs are valued in the context of regenerative medicine and disease modeling, especially for neurodegenerative disorder. iPSCs is a relevant tool to study the fundamental etiology of neurological diseases and also perform high-throughput drug screening for CNS disorders. In fact, several neurological diseases have been modeled using iPSCs, such as monogenic disorders and versions of complex diseases caused by known mutations have been modeled by iPSCs. Similarly, AD is another slow progressing disease with a poorly understood etiology and a lack of efficient therapeutic strategies.

Abstract

Buckyball is the first nanoparticle discovered in the year 1985 by the trio scientists Richard Smalley, Harry Kroto, and Robert Curl. Fullerene is a powerful antioxidant that reacts with free radicals that cause cell death. Fullerenes and their derivatives have the Antiviral activity to treat the HIV infection. Brain changes occur with these proteins are β-amyloid and tau tangles. The changes in Cerebrospinal fluid and blood indicate the earliest sign of Alzheimer’s disease (biomarkers) but the symptoms have not appeared. Ukrainian scientists discovered Carbon 60 or C-60 or Fullerene or Buckyballs. They are water-soluble, made progress on Alzheimer’s treating it with a Fullerene water solution.Through the Microinjection C60HyFn (0.46nmol/µl) is injected into the hippocampus reduces the deposition of β-amyloid in the pyramidal neurons of hippocampal CA1 neurons.

Introduction

Buckyballs also called Fullerene (C60). It is the first nanoparticle discovered in the year 1985 by the three scientists who work at the Rice University named Richard Smalley, Harry Kroto and Robert Curl. Buckyball is a common name for the molecule called Buckminsterfullerene [1]. These three scientists awarded a Nobel Prize in chemistry in 1996.

History of discovery of fullerene

Carbon atoms in a single hexagonal sheet of graphite are completely naked above and below. In the periodic table, we are having one atom which satisfies the bonding of the nearest neighbor’s in two dimensions. Carbon makes chemically stable two-dimensional, one-atom-thick membrane in a 3D [2]. Vaporization of carbon species is a technique used to produce and detect this molecule from the surface of a solid disk of graphite using a focused pulsed laser into a high-density helium flow. This resulting forms the carbon cluster [3].

C60 form is called a truncated icosahedron, which looks like a soccer ball. It consists of 12 pentagons and 20 hexagons. These 3 scientists conducted the study, with 3 graduate students. Smalley has started the experiment by guiding the local carbon in the apparatus. This is before the Kroto’s arrival, after 4 days Kroto has arrived. While Kroto directing the experiment the students ran the machine.

Two significant results arise in ten days of the experiment. Smalley put the first one as ‘Kroto’s long carbon snakes’, the second one is ‘a previously unknown molecule of pure carbon’. By using the helium as the carrier gas, the students noticed in Kroto’s words ‘something quite remarkable takes place” an odd peak in the mass spectroscopy of the molecule formed into vapour [4]. The peak occurred at sixty carbon atom and seventy carbon atom. C60 and C70 are very strong. Most experiments are focused on C60.

Alzheimer’s disease

Alzheimer’s disease is a type of brain disease. This disease cannot be noticeable quickly. Only after a few years the symptoms arises such as memory loss, language problem. The neurons in the brain get damaged which are involved in the thinking, memory, and learning. As time passes the symptoms get increased and the person is unable to do his daily activities. In the final stage of the disease, the person requires care. At this point, the individual is said to have dementia [7].

Brain changes occur with these proteins are β-amyloid present outside the neuron may contribute to cell death by interfering with neuron-to-neuron at the synapse, while tau tangles present inside the neuron does not allow any nutrients or other molecules inside the neuron [8].

Stages of Alzheimer’s disease

There are 3 stages. Preclinical stage, Mild Cognitive Impairment (MCI), Dementia.

Preclinical stage

This stage is still under investigation. The changes in Cerebrospinal fluid and blood indicate the earliest sign of Alzheimer’s disease (biomarkers) but the symptoms do not appear. Most research is required to identify the symptoms before it gets widespread in hospitals [9].

Mild Cognitive Impairment due to Alzheimer’s disease

People with MCI have brain changes i.e. elevated levels of β-amyloid. Non- modifiable risk factors and modified risk factors are identified for MCI. The non-modifiable risk factors include sex, age, and genetic factors, and modifiable risk factors such as level of education, vascular risk factors and imagining biomarkers. Only parents and friends can recognize the symptoms. A recent analysis found that after 2 years people with age 60 will develop dementia [10].

Dementia due to Alzheimer’s disease

Dementia can be noticeable by memory, thinking and behavioral symptoms identified in daily life. The person with dementia experiences multiple symptoms changing from period to period. These symptoms changes from mild to moderate to severe from person to person [11].

Diagnosis of Alzheimer’s disease

Doctors use several methods to determine whether a person is having a memory problem has ‘possible Alzheimer’s dementia’ or ‘probable Alzheimer’s dementia’. The doctor may ask the person or family or friends about the past reports. Overall health, diet, daily activities, changes in behavior and personality. Doctors conduct tests like Blood or Urine tests, CT or MRI scans, memory tests, genetic tests. The doctor prescribes the medicine to suppress the disease to some extent. It is not completely cured. For this reason, to treat Alzheimer’s disease, Ukrainian scientists discovered C60 water-soluble treatment.

Drinking Ukrainian Buckyballs [12]

The invention of drugs for the preparation and treatment of Alzheimer’s disease is the most important challenge for researchers in the 21st century. Synthesis of water-soluble fullerene and carbon nanotubes for drug development is growing rapidly in U.S.A, Asia, and Europe. Ukrainian scientists discovered Carbon 60 or C-60 or Fullerene or Buckyballs. They are water-soluble, made progress on Alzheimer’s treating it with a Fullerene water solution. This was approved as the Dietary Supplement by the Ukrainian Ministry of Health in 2010. They started producing drinking water in Ukraine with 0.0002mg/100ml of fullerenes.

The project aims to investigate the properties of stable antiamiloidn molecular colloidal aqueous solution of fullerene C60HyFn. The experimental models of Alzheimer’s disease is conducted under the direction of Igor Jakovljevic Podolsky. In 2007, he first discovered the neuroprotective properties of water molecules. He published his work in 2012 January revealed the influence of fullerene water causes the neurodegenerative process of memory loss.

For the first time by using transmission electron microscopy in vitro they found that water-soluble fullerene prevents and destroys the β-amyloid. By this, they concluded that the C60 in vitro anti-aggregation has a strong effect on the β-amyloid peptides.Through the Microinjection C60HyFn (0.46nmol/µl) is injected into the hippocampus reduces the deposition of β-amyloid in the pyramidal neurons of hippocampal CA1 neurons.

Conclusion

Alzheimer’s disease is a brain disease, which is occurring 15 to 20% of individuals after the age of 60. The symptoms are memory loss, unable to think and learn. Doctors use several methods to identify and diagnosis the disease. But it cannot be completely cured. For this reason the Ukrainian scientist discovered the Fullerene Water Solution and is injected into the hippocampus to reduce the β-amyloid peptide. We can assume that in the first half of the 21st century will be based on fullerene development for effective prevention and treatment of Alzheimer’s disease.

References

1. Smalley, Richard (1996-12-07) Discovering the fullerene. Nobel lecture p.97.nobelprize.org.
2. Kroto, H.W; Health, J.R; Brien, S.C; Curl, Smalley, R.E (1985). “C60 : Buckminsterfullerene”. Nature. 318(6042): 162-163.
3. Smalley, R.E. (1997). Discovering the Fullerenes (Nobel lecture). Angewandte chemie. International Edition in English, 36(15), 1594-1661.
4. Smalley, Great Balls of carbon, p.115
5. B.C.Yadav and Ritesh Kumar, International journal of Nanotechnology and applications: 2008; 1(2): 15-24
6. Ranian Bakry, Rainer M vallant, et al. International journal of Nanomedicine: 2007 Dec; 2(4): 639-649
7. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloids deposition, neurodegenerative and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol 2013; 12 (4): 357-67
8. Jack CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: Implications for sequence of pathological events in Alzheimer’s disease. Brain 2009; 132(5) 1355-65
9. Knopam DS, Parisi JE, Salviati A, Floriach-Robert M et al. Neuropathology of cognitively normal elderly. J Neuropathol EXP. Neurol 2003; 62:1087-95
10. Roberts R, Knopman DS. Classification epidemiology of MCI. Clin Geriatr Med 2003; 29:753-72.
11. Ward A, Terdiff S, Dye C, Arrighi HM. Rate of conversion from prodromal Alzheimer’s disease to Alzheimer’s dementia; A systematic review of the literature. .Demnt Geriatr Cogn Dis Extra 2013; 3:322-32
12. https://www.wired.com/2013/02/drinking-ukrainian-buckyballs-to-treat-alzheimers-disease/.

The film Still Alice deals with a very serious subject matter of a person whose life is turned upside down when she gets a diagnosis of early-onset Alzheimer’s disease. Throughout most of this film we can see an accurate portrayal of the symptoms associated with this crippling brain disease. During the course of the entire movie Alice Howland progressively goes through the three stages of Alzheimer’s disease. Although this movie depicts the human aspects of this degenerative condition exceptionally well, from a psychological standpoint there are some plot points that prove contradictory to the current real-world research findings for this condition.

When the film starts Alice is a world-renowned professor in linguistics studies at Columbia University and well known for conducting groundbreaking research on language acquisition in children. Later on, in the film it can be seen how her academic specialization has an ironic twist as she begins to suffer from language impairments which is one of the most severe hallmark symptoms of Alzheimer’s disease (What Are the Signs of Alzheimer’s Disease? n.d.). At first glance Alice seems to almost have a perfect life as she has a great marriage with a successful medical researcher and has three grown up children. But as the movie progresses Alice’s life begins to become an emotional rollercoaster as she starts to notice some unusual forgetfulness in her daily living. It first starts when she was speaking at UCLA and she momentarily could not think of a word during her speech. Alice seems to dismiss this incident but she becomes more worry when all the sudden she couldn’t figure out for a moment where she was while jogging close to Colombia where she teaches.

As someone who is well educated Alice refuses to dismiss her symptoms and decides to consult with a neurologist. He tells her that she is suffering from sporadic memory impairment which is not common for someone like her who has just turned fifty. The neurologist ask Alice questions regarding her family history and administers some cognitive test on Alice to see if she is able to recall or at best recognize a name and an address. Base on his observations the neurologist tells Alice that there is evidence of a sharp decline in her level of mental functioning and that she will need to be subjected to some brain imaging testing because she fits the criteria for early-onset Alzheimer’s disease (Glatzert & Lutzus, 2014). From there the film follows Alice’s every trial and tribulation as she tries to fight this vicious disease but as it progresses Alice is no longer able to continue living her normal everyday life. This can be best seen by how Alice meets with her department chair at Colombia and he tells her that her student evaluations were very negative and reads her some comments: One student wrote, “I was thoroughly disappointed. The content was muddled, and delivered with little focus or care.” Another one said that “The course was erratic. I had a hard time following Dr. Howland’s lecture. It seems like even she gets lost in them” (Glatzert & Lutzus, 2014). Alice then has no choice but to tell him that she has Mild Cognitive Impairment, and that she had been diagnosed with Early-Onset Alzheimer’s Disease. She tried to convince her chair that she will do a better job in the coming semester and that she would like to remain in the department for “as long as we all think it’s possible.” However, Alice memory ability begins to deteriorate at a fast pace and it becomes clear that many things in her life are no longer in her control. Consequently, Alice has to stop working. Alice’s condition also begins to take a toll on her personal life as she forgets a dinner date with her husband’s boss and spouse. As a result, her husband becomes frustrated and upset, Alice then becomes defensive and tells him that she has Alzheimer’s and that’s why she forgets. It seems that Alice is trying to avoid any social situations because she says that maybe that’s for the best: “I don’t know what I would have been like at a dinner party. I might not be able to remember names or answer simple questions—never mind get through an anecdote” (Glatzert & Lutzus, 2014).

Being face with a rapid deterioration Alice does her best to cope with her condition but also decides to formulate a plan to end her life once she comes to that point in her disease where she can no longer remember the answers to the questions that define who she is. Despite being a dramatic work of fiction “Still Alice” proves to hold many truths about people who are living with Alzheimer’s disease. Albeit there were instances throughout the film where there were some contradictions and inaccuracies to what current research says about Alzheimer’s disease. For instance, Alice seems to deteriorate way too quickly compare to most people who suffer from early-onset Alzheimer’s. Since there is data that shows that most Alzheimer’s patients tend to decline slowly, and most can live up to 10 years or more once diagnosed (Schwartz, 2018, chap. 10). Alice’s deterioration would appear to be quite extreme to anyone who has basic knowledge about how Alzheimer’s progresses. In the movie there was a scene that stood out to me where Alice’s neurologist presents an contradictory explanation as to why Alice is declining so quickly. When John her husband tells the neurologist that they are alarmed of how rapidly the decline was taking place the doctor explained that this was commonly seen in people with Early-Onset Alzheimer’s additionally he said that among people who have a high level of education, the progression can become much faster. However, this goes against the idea of cognitive reserve in which research shows that people like Alice who are highly educated and intellectually well versed have a greater cognitive reserve which gives them the ability to off set and fight some of the symptoms of the degenerative brain changes and neuronal damage associated with Alzheimer’s or other brain diseases (Harvard Health Publishing, n.d.).

Although this film takes some liberties in portraying Alzheimer’s disease for the most part it sticks to the truth and does a good job at presenting the overall human struggles and limitations that stem from this condition. For instance, in the movie Alice is not only burden with her own condition but also the idea that her kids could inherit it from her. This and other ideas presented in this film appear to be back up by real-world research on the genetic and environmental component that could contribute to the development of Alzheimer’s (Alzheimer’s Disease Genetics Fact Sheet, n.d.). Additionally there is a scene where the neurologist discusses the idea of how amyloid plaques within the brain is a common feature of Alzheimer’s but not a determining factor because even people who don’t have the disease can have such plaque buildup, hence why brain scans are used in conjunction with other indicators of the disease to make a final diagnosis (Glatzert & Lutzus, 2014). In closing, as a viewer I enjoyed this film because it does an exceptional job at conveying what it’s like to have Alzheimer’s disease and takes us through each of the three main stages associated with the condition.

The film makes emphasis of what it feels to be in the shoes of someone with Alzheimer’s by having scenes in which Alice is asked to speak about the disease and her journey. Some of the scenes which demonstrate this is when Alice’s daughter Lydia asks her: “What’s it like? What does it actually feel like?” Alice answers: “I have good days and bad days. On my good days, I can almost pass for a normal person. And on my bad days, I feel like I can’t find myself. I’ve always been so defined by my intellect, my language, my articulation, and now, sometimes I can see the words hanging in front of me but can’t reach them, and I don’t know who I am and don’t know what I’m going to lose next.” (Glatzert & Lutzus, 2014). This scene ends with Alice thanking her daughter for asking her how she felt. I think this is an important part of the film as all viewers can relate to it in one way or another because we all long for understanding, and this conveys how sometimes a small act like this can bring dignity to someone suffering from Alzheimer’s. There is also a powerful scene of Alice giving a speech at the Alzheimer’s Association in which she speaks of her harrowing personal journey of having to live with Alzheimer’s. After all, it can be argued that for the format and genre in which this condition is portrayed the inaccuracies found within the story line are very minor for this type of work. For this and many other reasons most people like myself would agree that this movie does in fact offers a true-to-life portrayal of Alzheimer’s disease which manages to capture not only the human aspects of the disease but also some of the scientific and psychological aspects behind Alzheimer’s disease.

References

1. Alzheimer’s Disease Genetics Fact Sheet. (n.d.). Retrieved from https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet. Glatzert R. (Producer), & Lutzus L. (Director). (2014) Still Alice [Motion Picture]. United States: BSM Studios
2. Harvard Health Publishing. (n.d.). What is cognitive reserve? Retrieved from https://www.health.harvard.edu/mind-and-mood/what-is-cognitive- reserve.
3. Schwartz, B.L. (2018) Memory Foundations and Applications Third Edition. Los Angeles: SAGE publications, Inc. What Are the Signs of Alzheimer’s Disease? (n.d.). Retrieved from https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease.

With the development of aging in society, the incidence of senile psychosis is getting higher and higher: mainly manifested in population of both common elderly diseases: Alzheimer’s and Parkinson’s rising. In 2015, 8.5% of the world’s population was over 65 years old, and by 2050, it will jump to nearly 17% of the global population. However, in 2016, 61 million people worldwide suffered from Parkinson’s disease, and it is estimated that the population of Alzheimer’s patients will reach 115.4 million in 2050. Additionally, both Alzheimer’s and Parkinson’s disease is incurable mental illness that drugs and others treatment just only can reduce the worsening progression, and both disease have not yet been fully understanding of their causing factors. Fortunately, the best treatment that everyone can do it is giving the elderly understanding and companionship.

Relationship between mental illness and aging

The simplest answer to the aging of living organisms is that living organisms (such as the human body) are like a very complicated and sophisticated machine. The machine takes a long time and always causes wear and tear, exposing a variety of problems. The same is true for people, whether they are organs or cells, the molecules inside are gradually damaged, the waste is constantly accumulating, and finally there is always a loss of function. According to a report, the global population reached 7 billion in 2012, the population aged 65 and over was 562 million (8.0%); In 2015, 8.5% of the world’s population was over 65 years old, and by 2050, it will jump to nearly 17% of the global population (Kowal, Goodkind, & He, 2016). Normal aging is unstoppable and is the procedure of reduction of various psychological functions. However, in the normal aging population, patients of senile psychosis have a variety of psychological activities in a state of confusion, and intelligence is obviously impaired. Senile psychosis can lead to sudden changes in behavior, self-injury, impulsive, no self-awareness and other mental symptoms. The cause of senile psychosis is due to cerebral arteriosclerosis, cerebral ischemia, hypoxia and metabolic disorders, causing brain tissue atrophy, mental decline, personality changes and mental disorders; among senile psychosis, senile dementia and arteriosclerotic mental disorders are more common (Eizaguirre, Rementeria, González-Torres &, Gaviria, 2017). The main points of treatment for senile psychosis are not taking medication and life conditioning, but more importantly, need to be patiently cared for by relatives around them. With the development of aging in society, the incidence of senile psychosis is getting higher and higher: mainly manifested in population of both common elderly diseases: Alzheimer’s and Parkinson’s rising.

Alzheimer’s disease

It is estimated that the population of people over the age of 60 will reach 2 billion in 2050, accounting for 22% of the global population; after the age of 65, the prevalence rate is doubled every five years, and data on prevalence and morbidity predict that the number of people with dementia worldwide will continue to increase: In 2001, there were 24.3 million people over the age of 60 with Alzheimer; the total number of Alzheimer patients worldwide in 2010 was approximately 35.6 million; Alzheimer’s patients will reach 65.7 million in 2030; In 2040, the number of patients will reach 81.1 million; In 2050, it reached 115.4 million; The number of new Alzheimer patients is close to 7.7 million per year, that is, a new dementia patient appears every 4 seconds (World Health Organization and Alzheimer’s Disease International, 2012).¬¬

Alzheimer’s cause：Genetic factors

Scientists have not yet to fully understand the causes of Alzheimer’s disease. However, with the increasing understanding of the disease, we have found that genes are becoming more and more important in this disease. Alzheimer’s disease is an irreversible, progressive brain and mental disease. Alzheimer’s disease can be divided into two types: early-onset Alzheimer’s disease and late-onset Alzheimer’s disease. Both are related to genes. Early-onset Alzheimer’s disease is quite rare, accounting for only a minority of Alzheimer’s patients, mainly between the ages of 30-60. One of the mutant genes is passed on to one of the parents, and the next generation will almost certainly develop early-onset Alzheimer’s disease. If one of the parents is familial Alzheimer’s, the chance of getting the disease in the next generation is as high as 50% （Jarvik et al., 2008）. Late-onset Alzheimer’s disease, the vast majority of Alzheimer’s disease is a late-onset, occurring after the age of 60. Late-onset Alzheimer’s disease has not yet found a specific pathogenic gene, but studies have shown that APOE ε4 increases the risk of illness. APOE ε4 can be detected in patients with late-onset Alzheimer’s disease; those with inheritance of one or two APOE ε4 dual genes have earlier disease progression than those without (Bird, 2008).

Alzheimer’s cause：β-amyloid（also Environmental factors and behavior factors）

Scientists have long believed that β-amyloid has a highly toxic effect on brain synapses and is one of the causes of Alzheimer’s disease. The reason is that β-amyloid causes blockage and damage to synaptic transmission. Some recent studies have shown that Alzheimer’s disease is actually a self-protective response mechanism of the brain, and β-amyloid is actually protective. The true cause is that the body’s function is weakened with aging, the decreasing of resistance to inflammatory infections, the lack of supporting nutrient factors for synapses, and the long-term accumulation and exposure of toxic substances trigger the brain’s self-protective reaction mechanism to synthesize β- amyloid (Bredesen, 2017a).

Alzheimer’s disease is not a single disease, but a disease that is complex and combined with multiple causes and diseases. Like vascular dementia, frontotemporal dementia, Lewy body dementia, subjective cognitive decline and mild cognitive decline, all of the above diseases are closely related to Alzheimer’s disease (Karantzoulis & Galvin, 2011a).

Alzheimer’s syndrome

In patients with Alzheimer’s disease, the symptoms of each patient are different. However, the symptoms of patients with Alzheimer’s disease can be generally concluded as follows: prosopagnosia, patients with Alzheimer’s disease lose the ability to recognize or remember faces; patients with Alzheimer’s disease found their own spirit and vitality Significantly decline; loss of interest in reading: patients with Alzheimer’s disease found themselves losing the ability to understand and participate in complex conversations; patients with Alzheimer’s disease found themselves decreased the ability of reaction; vocabulary decline and word confusion, patients with Alzheimer’s disease found themselves the speed at which the information processing was reduced (Bredesen, 2017b). Because the symptoms of Alzheimer’s disease are similar or overlapping with the symptoms of other elderly diseases, and the symptoms of Alzheimer’s disease in the elderly will change with the severity of Alzheimer’s disease, under such circumstances, doctors have difficulties in diagnosing between patients with Alzheimer’s disease or patients with other elderly diseases, which also causes the difficulties to judge the cause of the Alzheimer’s disease (Karantzoulis & Galvin, 2011b).

Alzheimer’s treatment

Medically, Alzheimer’s disease is still considered to be a disease. Therefore, it is usually treated with donepezil or memantine hydrochloride. However, the pathological problem of Alzheimer’s disease cannot be fundamentally solved, nor can it be prevented from worsening, and the disease cannot be cured. Until now, there is no drug for treating Alzheimer’s disease. The disease will continue to develop even after took the drug. Over time, the brain limits the efficacy of the drug, which the drug will become useless eventually；There are also side effects of the drug, including diarrhea, nausea, vomiting, and the drug itself may also become a lure of cognitive decline and thus aggravate the condition (Schneider et al., 2014).

Parkinson’s disease

Nervous system diseases are the world’s leading source of disability, and Parkinson’s disease is the fastest growing disease among these diseases. Parkinson’s disease is a common degenerative disease of the nervous system. It is more common in the elderly. The average age of onset is about 60 years old. Parkinson’s disease is rare in young people under 50 years of age. The number of people with Parkinson’s disease in 1990 was 25 million; In 2016, 61 million people worldwide suffered from Parkinson’s disease, of which 29 million were women and 32 million were men, and the incidence of men with Parkinson’s disease is 1 to 4 times that of women (GBD 2016 Parkinson’s Disease Collaborators, 2018).

Parkinson’s cause：Environmental factors and behavior factors

The exact cause of Parkinson’s disease is still unknown. Genetic factors, environmental factors, behavior factors and ageing are all considered as potential causes. Neurodegenerative diseases, especially Parkinson’s disease, may be affected by the environment and daily activities. Scientists have identified a number of environmental risk factors, including pesticides, solvents, and PCBs associated with increased risk of Parkinson’s disease. Behavioral and lifestyle factors such as smoking: longer smoking times or more cigarette smoking are associated with lower Parkinson’s disease risk, and caffeine intake is Often associated with a reduced risk of Parkinson’s disease: the risk of drinking high coffee for men is reduced by nearly 60% (Obeso et al, 2017).

Parkinson’s cause：Genetic factors

Young onset Parkinson’s disease refers to people with Parkinson’s disease before they are 40, and later onset Parkinson’s disease is referred to the patient with Parkinson’s disease after 50 or 60. Genetic causes for young onset Parkinson’s disease have been implicated; it appears genetics may play a greater role in the development of Parkinson’s disease in those with young onset. scientist have found six genes that can cause Parkinson’s disease when mutated: SNCA, LRRK2, Parkin, PINK1, DJ-1, and ATP13A2; SNCA and LRRK2 are responsible for autosomal-dominant PD forms; thus far the two most common genetic causes of Parkinson’s disease are mutation of Parkin and LRRK2; though these are still relatively rare, Parkin mutation appears to be responsible for 20% of young onset Parkinson’s disease where patients have a strong family history of disease and onset occurs below age 30; mutation of LRRK2 seems to be responsible for approximately 2% of typical late onset Parkinson’s disease (Klein & Westenberger, 2012).

Parkinson’s syndrome

In 1817, British doctor James Parkinson first described the disease in detail; his clinical manifestations include resting tremor, bradykinesia, myotonia and posture gait disorder; Patients can also be accompanied by depression, constipation, and sleep disorders symptom; the diagnosis of Parkinson’s disease depends mainly on medical history, clinical symptoms and signs (Goetz，2011). Sleep disorders are one of the most common manifestations of Parkinson’s disease, and patients often feel tired and weak. Patients often want to sleep but can’t sleep. Although sleep disorders of Parkinson’s disease have most of the same characteristics as sleep disorders in the general population, in diagnosis: insomnia, daytime Excessive lethargy, restless leg syndrome and periodic limb movement, REM sleep behavior disorder, sleep-disordered breathing, and symptoms of circadian rhythm disorders can be diagnosed with the potential manifestations of Parkinson’s disease (Chahine, Amara, & Videnovic, 2017).

Decreased cognitive ability in Parkinson’s patients is one of the most obvious symptoms. 20–50% of patients with Parkinson’s disease are diagnosed with mild cognitive impairment; cognitive deficits in Parkinson’s disease often affect executive function, attention, visual spatial function, and processing speed; however, older people show differences in cognitive test performance, especially in response time testing and distraction and working memory testing (Goldman et al, 2018).

Parkinson’s treatment

Drug treatment is the most important treatment for Parkinson’s disease. Surgical treatment is an effective supplement to medication. Rehabilitation, psychotherapy and good care can also improve symptoms to some extent. The current treatments are mainly to improve symptoms, but still can not prevent the progression of the disease. Levodopa is still the most effective drug. However, using medication means you can never stop taking it. Patients who discontinue the drug can cause dopamine agonist withdrawal syndrome (DAWS); the symptoms of DAWS are similar to those of withdrawal from other psychostimulants; they may include anxiety, panic disorder, social phobia, square phobia, fatigue, Irritable, restless, depressed, eager for drugs and suicide (Samuel et al, 2015).

Conclusion

The inevitable global population aging, irreversible procedure of growing old and incurable mental illness like Alzheimer’s and Parkinson’s disease in the elderly, and as aging elderly people are more likely to suffer from mental illness are natural law and the problem needed to confront. Faced with the laws of nature and power, the science and power of mankind are very small. Fortunately, we have better ways and means. People are emotional animals; we will take care of the elderly. After reading so many research papers and books, I know that medical treatment is very important. But more important is to give the elderly understanding and companionship. It is necessary to have patience to take care of the inconvenience of the elderly. Patients with Parkinson’s disease may be inconvenient in some way. It is best to let people stay with them without any omissions. However, as a family member, you must maintain an optimistic attitude, face a patient’s mentality, and pay more attention to the patient, because at this time the patient is most afraid of seeing the family members’ sighs, most afraid of being left out.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder found among older adults at the age of 65 and above (Schwamborn, 2018). Symptoms of AD are memory loss, cognitive declination, disorientation, language deficit, impaired concentration, personal hygiene and self-care declination as well as behaviour and personality changes (Bature, F., Guinn, B. A., Pang, D., & Pappas, Y, 2017).

At this point of time, the exact causes of AD are still not being publicized. However, researchers believe that the early-onset of AD are caused by the genetic mutations related to the production of beta-amyloid protein (Robert V. Kail, 2019). Also, genetic inheritance can be a component that had caused early-onset AD. Although causes of later-onset AD are more complicated and had not been well documented yet, researchers are focusing on studying the relationship of amyloid plagues and neurofibrillary tangles with the AD patient’s brain (Munoz, D. G., & Feldman, H, 2000). According to the beta-amyloid cascade hypothesis (Robert V. Kail, 2019), when beta-amyloid deposits causes neuronal death severely enough, AD is established.

Having no effective treatment for AD patients, there is still ways to alleviate their symptoms. Although drugs provide little long-term relief, cholinesterase inhibitors are an approved drug treatment that can be used to treat AD patients (Briggs, R., Kennelly, S. P., & O’Neill, D, 2016). Behavioural strategies such as putting large calendars to help AD patients with time orientation and memory interventions based on the E-I-E-I-O approach can effectively help AD patients (Robert V. Kail, 2019).

Being the second most common form of progressive neurodegenerative disease, Parkinson’s disease (PD) normally first develops at the age of 60 (DeMaagd, G., & Philip, A. , 2015). Symptoms of PD include tremor, rigidity, slowness of movement, difficulty chewing, swallowing, speaking and impaired coordination (National Institute on Aging (NIA), 2017).

Furthermore, PD is caused by the deterioration of dopamine production in the midbrain (Robert V. Kail, 2019). PD happens when impaired neurons in the brain produces lesser dopamine that is responsible for movements and thus resulted in movement difficulties. Moreover, features of PD include the loss of nerve endings that produce norepinephrine and the presence of Lewy bodies found in brain cells (DeMaagd, G., & Philip, A. , 2015). According to (National Institute on Aging (NIA), 2017), many researchers had now agreed that PD is caused by a combination of genetic factors and environmental factors.

The most common type of therapy given to PD patients is the Levodopa therapy (Jankovic, J., & Aguilar, L. G., 2008). To replenish the declining supply of the patients’ brain, Levodopa is a type of medication that can be used by nerve cells to create dopamine. Moreover, for PD patients that have motor complications and do not respond well with medications, Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) is another option for them (Anna Castrioto, 2014). DBS is a surgical procedure which implants electrodes into the patient’s brain and connects them to the programmable neurostimulator. Neurostimulator and the electrodes painlessly stimulate the brain, helping many of the movement-related symptoms such as trembling and slowness of movement to cease (National Institute on Aging (NIA), 2017)

The clinical symptomatology of Alzheimer’s disease (AD) is considered to be the result of an extensive destruction or disorganization of the cerebral cortex, as the patient’s cognitive functions become impaired. Late onset Alzheimer’s disease affects 5-10% of people over the age of 65 years old and while the case for this disease has not yet been fully understood, it is believed that a combination of genetic, environmental and lifestyle factors affects the risk for developing the disease. Researchers have not yet found a specific gene directly linked to sporadic AD however, patients with the Apolipoprotein E (APOE) specifically the E4 allele, located on chromosome 19 are twelve times more likely to develop the disease according to the Alzheimer’s Drug Discovery Foundation.

The neurodegenerative disease is pathologically characterised by failure of the normal protein synthetic machinery of the cell, with consequent abnormal post-translational processing of the amyloid precursor protein (Pearson and Powell, 1989). Therefore, leading to the extracellular deposition of Aβ into toxic plaques and intraneuronal accumulation of abnormal tau protein forming together creating neurofibrillary tangles (NFT). Early onset familial Alzheimer’s disease (FAD) is inherited as an autosomal dominant trait and accounts for 10% of AD cases. Genetic linkage studies have mapped the formation of abnormal amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2) genotype mutations on chromosomes 21,14 and 1. FAD progresses more rapidly, eliciting beta-amyloid peptide (Aβ) aggregation in earlier years, diagnosis can be as early as 20-30 years of age in this case. The APP mutation is located within the proximity of cleavage sites for β- secretases and y- secretases increasing production of Amyloid peptide, excessive amounts of this toxic protein leads to the death of nerve cells. Comment by Briana Hindemith: Proteins being synthesised by ribosomes translating mRNA into polypeptide chains – abnormal therefore indicating failure of this process Comment by Briana Hindemith: Integral membrane protein expressed in many tissues and concentrated in the synapses of neurons – generates Beta Amyloid (AB) polypeptide that is the primary form of Amyloid plaques found in AD brain Comment by Briana Hindemith: The formation of AB in large clusters at a progressively earlier rate

In the mid-1970s the first neurochemical that underlined dementing symptoms was discovered from the observation of neurons synthesising and releasing acetylcholine. While observations continued it became apparent that there was significant decrease in degradative enzymes and acetylcholinesterase in the limbic and cerebral cortices (Selkoe, 2001). This discovery lead to pharmacological research focused on attempting to enhance the acetylcholine levels primarily by inhibiting degradative enzymes. Since this past discovery pharmacological drugs such as Acetylcholinesterase inhibitors – donepezil, rivastigmine and galantamine are prescribed to patients with mild AD to temporarily ameliorate symptoms but unfortunately do not stop the progression of the disease. Currently in present day, there still is no modifying treatment available to patients suffering from AD however, gene therapy has been identified as a possible treatment for the Neurodegenerative disease. Studies conducted on the nerve growth factor (NGF) prove to exert pharmacological effects on particular cholinergic neurons known to atrophy in AD. NGF production is synthesised in the hippocampus and the cerebral cortex before being secreted to axon terminals in the basal forebrain cortical neurons. The aim of this treatment is to maintain the physiological concentration of NGF to support the growth and maintenance of Cholinergic neurons that help aid with the reduction of AB levels within the basal forebrain. This treatment can be approached using either ex-vivo or in-vivo methods. By treating the disease with an ex-vivo approach fibroblasts are transduce with retroviral vectors and injected into the nucleus basalis of patients, in an attempt to improve cognitive functions without adverse effects (Nilsson et al., 2010).

However early-stage clinical trials testing in vivo methods as an approach to treating Alzheimer’s disease have shown significant advantages. Alternative viral vectors such as recombinant adeno-associated (rAAV) have been developed to replicate genetic information to form double-stranded DNA which is then transcribed to produce the gene of interest. These vectors proceed to infect non-dividing neural cells with extensive studies showing for the virus to be non-toxic and weakly immunoreactive. Clinical research has been conducted on Aβ- degradation enzymes such as β- secretases and y- secretases inhibitors that could act as in-vivo treatments within the cortical neurons to decrease both intra and extra cellular levels of Aβ. However, due to the lengthy procedures required for ex-vivo gene delivery the in-vivo approaches are more likely to be favoured for treatment in the future. In the case of FAD patients, studies have indicated that individuals carrying the E2 allele within the APOE genotype reduce their risk of developing AD by 40%. As the APOE genotype performs neuroprotective and neurotrophic functions within the normal aging brain, the E2 allele binds to Aβ with greater affinity allowing for isoforms to form and regulate Aβ clearance through neurons, microglia or delivery to the blood-brain barrier (BBB) (Rebeck, Kindy and LaDu, 2002). Clinical tests have begun with an injection of a virus containing the APOE 2 gene into patients with FAD, aim of the treatment is to bath the brain in gene replacement therapy by relying on this virus to send instructions to re-code DNA. However, this treatment would be administered during the pre-symptomatic period aiming to stop the disease before it begins. While there are currently many treatments being investigated and researched there is still unfortunately no specific treatment for the prevention of AD.

AD remains a looming health crisis despite the efforts and research surrounding the neutron dysfunction and neurodegeneration that accompanies AD. Moving forward with future technology and the opportunity of gene therapy possibly preventing or curing AD there are multiple ethical issues surrounding the future treatment of this disease. It is easy to imagine situations where by adding what is presumed to be the beneficial gene or by removing the mutated gene that there is high controversy surrounding the topic. Speaking on behalf of a religious perspective 58% of individuals polled by CNN believe that by altering human genes is against the will of God (Ndsu.edu, 2019). Its an interesting issue to be raised as God has distinctively designed each and every human on this earth with a specific plan and purpose, he was holy and wise when doing so and by conducting treatments such as gene therapy we scientifically would be changing his divine creation. However, a world free from suffering and disease is an ideal for humanity, with AD currently increasing as one of the 21st Century’s greater medical issues. Currently over 5.4 million Alzheimer’s patients are receiving medical care incurring at a cost as high as $200 billion a year. Pharmacoeconomics studies the costs and benefits of therapies and technologies like gene therapy and evaluate the importance of them in regard to the global economic pressures (Issa and Keyserlingk, 2000). Ethical reviews on gene therapy and AD patients increase addressing the issue of future treatment availability and the costs/outcomes on medical care. With the possibility for the expenses of the treatment creating a larger economical separation between upper- and lower-class communities. Finally the ethical dilemma of DNA banking arises, as genotyping often involves the long-term storage of DNA for future analysis. Related issues of autonomy, privacy and informed consent ascends specifically due to the insurance industry’s interest in genetic information as it had the potential to predict future healthcare risks.

Furthermore, when deciding whether gene therapy would be appropriate and beneficial to fund as a treatment for AD the potential benefits need to outweigh the risks. Personally I believe if monitored by the government and medical society gene therapy has the opportunity to produced exceptional results and success specifically when treating AD.

BIBLIOGRAPHY

1. Issa, A. and Keyserlingk, E. (2000). Apolipoprotein E Genotyping for Pharmacogenetic Purposes in Alzheimer’s Disease: Emerging Ethical Issues. The Canadian Journal of Psychiatry, 45(10), pp.917-922.
2. Nilsson, P., Iwata, N., Muramatsu, S., Tjernberg, L., Winblad, B. and Saido, T. (2010). Gene therapy in Alzheimer’s disease – potential for disease modification. Journal of Cellular and Molecular Medicine, 14(4), pp.741-757.
3. Rebeck, G., Kindy, M. and LaDu, M. (2002). Apolipoprotein E and Alzheimer’s disease: The protective effects of ApoE2 and E3. Journal of Alzheimer’s Disease, 4(3), pp.145-154.
4. Selkoe, D. (2001). Alzheimer’s Disease: Genes, Proteins, and Therapy. Physiological Reviews, 81(2), pp.741-766.
5. Ndsu.edu. (2019). The Ethics of Gene Therapy. [online] Available at: https://www.ndsu.edu/pubweb/~mcclean/plsc431/students/bergeson.htm [Accessed 7 Nov. 2019].
6. Pearson, R. and Powell, T. (1989). The Neuroanatomy of Alzheimer’s Disease. Reviews in the Neurosciences, 2(2), pp.101-122.