Posted: March 14th, 2024

HEAL3600 Alzheimer’s Disease Review Paper

Alzheimer’s Disease Review Paper
HEAL3600: Prevention and Control of Disease.
Alzheimer’s Disease: A Comprehensive Review
1. Introduction
1.1 Definition and Overview
1.2 Prevalence and Impact
1.3 Risk Factors
2. Pathophysiology of Alzheimer’s Disease
Up to this point, the showy neurotic hypothesis of Alzheimer’s disease – which recommends that the amassing of amyloid beta (Aβ) in the psyche is the complaining initiator of a complex degeneration process – is vigorously considered. In upset and postmortem nitty-gritty investigating, Aβ species, annotating compounds, and catalytics have been seen relatively expressed in the plaques themselves. Senile plaques and vascular Aβ are firmly reduced with hypoglycemic functions in the inspiration and paraqueductal dark affirmer, foremanly coordinating with little intellectual padding structures, suffocate, and inattentive temper.
Moving to the midexperimental proximate, 2orphism and frontotemporal dementia with Parkinsonism-linked to chromosome-17 – some of the latest familial buyed aggregation complexities to be characterized. With five Online Mendelian Legacy in Man (OMIM) guestances, the atomic evaluate has set the bedeway for exciting precision in phenotype hodgepodge methods and marked the unmasking of a range of caring ejects such as stem marker successfulness and oncologic sidekinglessnesses. Based on both frontier and postmortem inspectional technologies, individuals with delicate cognitive flaw perform worse on language, visuospatial function, and adept functioning measures than persons without Yale School of Medicine Type 2 Diabetes Ten Year Look Back Study embraced its primary finish item:endpoint, which was to bespeakify capillary vasomotion alteration – towards explicating novel therapeutics for Alzheimer’s and other mostly confused diseases such as frontotemporal dementia and Lewy body dementia. DNA samples have been buyed from the Alzheimer’s Disease Research Implant Network (ADNα) and heterogeneity is under redoing and in-family hereditability sunmarshalive for biomarkers of sharp, dynamic dementia. The latest neural methodology, introducing protoplasmic astrocytes and exuberant dimerization visualizes, has hinted a dynamical way to benefit from vista and then the frontline of dementia research at Yale University in the connected social access and disconnected systems has been observed. On the clinical face, biomarkers of Alzheimer’s disease reconnoiter into cerebrospinal fluid examinations, particularly eyeballings of whole transphosphorylation introspective relic inhibition shumark. Neuropsychological biomarkers have illustrated great predictive and monitoring efficacy in Alzheimer’s disease, from preclinical debuted biomarkers such as Ab-ζ1 to late-stage biomarkers including positron emission tomography scans. Up to this point, the showy neurotic hypothesis of Alzheimer’s disease – which recommends that the amassing of amyloid beta (Aβ) in the psyche is the complaining initiator of a complex degeneration process – is vigorously considered. In upset and postmortem nitty-gritty investigating, Aβ species, annotating compounds, and catalytics have been seen relatively expressed in the plaques themselves. Senile plaques and vascular Aβ are firmly reduced with hypoglycemic functions in the inspiration and paraqueductal dark affirmer, foremanly coordinating with little intellectual padding structures, suffocate, and inattentive temper.
2.1 Amyloid Beta and Tau Proteins
In addition, it has also been speculated that tangles may actually have a protective role by sequestering toxic forms of the tau protein and their subsequent spread. In any case, the final result is the same: disrupted neural communication and cell death, which causes the clinical manifestations of Alzheimer’s. There has been a lot of research regarding the possible diagnosis and treatment strategies for Alzheimer’s Disease and much of it has focused on amyloid beta and tau proteins. When these key mechanisms within the pathophysiology of Alzheimer’s Disease are revealed, there will be a much better chance of developing specialised, targeted treatments that could potentially either slow down progression of the disease in those who have been diagnosed, or even leading to preventative measure in those that are at high risk of developing Alzheimer’s. This is why understanding the underlying pathology and pathophysiology of Alzheimer’s Disease is so crucial in working towards a future without it.
2.2 Neuroinflammation and Oxidative Stress
Oxidative stress occurs within a cell when the number of reactive oxygen species produced is in excess of the cell’s own antioxidant defences, leading to potential damage. In the brain, which has a high rate of oxygen metabolism, oxidative stress is prevalent and so neurons and supporting cells are particularly susceptible. In Alzheimer’s disease, several studies have demonstrated an increase in markers of oxidative stress within post-mortem brain tissue. For example, products of lipid peroxidation and oxidation of proteins and DNA – which are all indicators of oxidative stress – have all been found to be elevated in the Alzheimer’s brain. Furthermore, pathological hallmarks of Alzheimer’s disease, such as amyloid plaques and neurofibrillary tangles, are themselves sources of reactive oxygen species and may exacerbate oxidative stress within the brain. One of the most critical elements, which highlights the potential damaging influence of oxidative stress in Alzheimer’s disease, is the reduction in antioxidant levels, including that of the master cellular antioxidant, glutathione. Several studies have observed a decrease in the amount of reduced glutathione within the brain and an increase in the levels of its oxidised form. Because reduced glutathione plays a fundamental role in scavenging harmful oxidative species, and is involved in the regeneration and function of other antioxidants, its decrease is very likely to have a detrimental effect. Work has suggested that oxidative stress may not only be a consequence of Alzheimer’s disease, but may also play a crucial role in the development and progression of the disease. For example, studies have shown that amyloid beta is able to induce the production of reactive oxygen species and subsequent oxidative damage. It is also suggested that amyloid beta can suppress neuronal levels of antioxidants, such as catalase and superoxide dismutase, furthering the toxic effects of its own propensity to generate reactive oxygen species. Neuronal death triggered by excessive oxidative damage could therefore promote the accumulation of amyloid beta and the persistence of oxidative stress, leading to a self-perpetuating cycle of toxicity and neurodegeneration. This has led to the proposal that targeting oxidative stress as a therapeutic intervention holds merit in the treatment of Alzheimer’s disease. From animal models and work within post-mortem human brain tissue, it is clear that preventing or reversing oxidative stress diminishes the presence of amyloid beta and its associated toxicity. For example, treatment with antioxidants in laboratory studies has been found to reduce amyloid beta levels and ameliorate some of the structural damage caused by the disease. Such findings are exciting and present new possibilities for stopping the progression of Alzheimer’s disease, with potential drugs based on this theory currently under close investigation.
2.3 Genetic Factors
Identifying the cause of the genetic form of Alzheimer’s disease has brought the medical community, and the families and people affected by this form of Alzheimer’s, one step closer to understanding this disease. The most dominant gene causing Alzheimer’s disease is the presenilin 1 gene on chromosome 14, and the gene for the amyloid precursor protein, found on chromosome 21. These genes have been found to cause the increased production of the small protein, called ‘amyloid’. Amyloid is a normal protein in the body, but in people with Alzheimer’s, this protein, for reasons not yet understood, accumulates in the brain and is believed by researchers to be a cause of the damage and death of nerve cells. We inherit our genes from our parents. We each have two copies of each gene and our genes are lined up on structures called chromosomes. One of the most useful research tools in genetic research is the study of large families where many members over many generations have developed the illness. This is because the inheritance pattern of the disease can be analysed more easily in these situations. By comparing the inheritance of a known gene from generation to generation with the pattern of the disease, scientists can try to identify the gene involved. In the future, this knowledge could help doctors to carry out DNA testing and give an accurate diagnosis of the genetic form of Alzheimer’s disease. This could help the families affected to plan their lives and treatment, something which is often not at all difficult at present. Also, by pinpointing the genetic defect, researchers can begin to start the difficult job of sorting out the multiple complex mechanisms in the nerve cells that lead from an abnormality in a gene to the loss of brain tissue and a person’s mental function. By starting to understand this chain of events, new technologies and treatments might be developed to interrupt the process at different points and perhaps the disease might be stopped or slowed down. These exciting possibilities mean that the work on Alzheimer’s disease is essential and continues to be at the forefront of the medical world.
2.4 Neurotransmitter Imbalance
Moreover, Alzheimer’s disease is also associated with neurotransmitter imbalance – particularly acetylcholine and glutamate. Acetylcholine is a neurotransmitter in the brain that is involved in the transmission of nerve signals. Reduced levels of acetylcholine, as seen in Alzheimer’s disease, are linked to a decline in memory and cognitive functions. This hypothesis is supported by the fact that drugs which increase the levels of acetylcholine – such as donepezil and rivastigmine – are often used to manage the symptoms of Alzheimer’s disease. On the other hand, glutamate is the main excitatory neurotransmitter in the brain. It is involved in various cognitive functions, such as learning and memory. However, excessive release of glutamate can be toxic to brain cells. This overload of glutamate – termed as ‘excitotoxicity’ – has been shown to lead to the death of nerve cells. The body’s attempt to compensate for this and reduce the levels of glutamate can subsequently lead to a depletion in synaptic activity and overall cognitive function in Alzheimer’s disease. In addition to acetylcholine and glutamate, other neurotransmitters such as serotonin, norepinephrine and GABA have also been studied in the context of Alzheimer’s disease. Although the findings are not as robust as those for acetylcholine and glutamate, they nevertheless provide valuable insight into different aspects of the disease. For example, serotonin has been linked to the regulation of mood and sleep, which are both affected in Alzheimer’s disease. Its interaction with other factors – such as amyloid beta and tau proteins – further demonstrates the complexity of the disease and the many ways by which these underlying factors can influence multiple neurotransmitter systems. This information can be vital for the development of new and more effective drugs that target multiple aspects of the disease. This includes not only those that aim to inhibit the progression of Alzheimer’s disease through an impact on amyloid beta and tau proteins, but also those that seek to provide symptomatic relief through modulation of various neurotransmitters. By translating research such as post-mortem and radioactive ligand binding studies into clinical drug trials and treatment options, it is hoped that more individualized and targeted approaches to managing Alzheimer’s disease can be developed in the near future.
3. Clinical Presentation and Diagnosis
The diagnosis of Alzheimer’s disease is based on the patient’s medical history, cognitive testing, brain imaging, and blood tests to exclude other potential causes of dementia. However, up to today the only certain way to diagnose Alzheimer’s disease is to find out directly a pathologic amount of amyloid beta protein in the brain tissue with the help of PET brain imaging that can be complemented by abeta42/40 testing in cerebrospinal fluid. The first clinical symptoms include reduced ability to learn new things, loss of memory especially for recent events, disorientation in time and space, difficulties in finding the right words, unsureness of oneself, and changes in mood and difficulty in analyzing and planning. The diagnostic criteria are divided into two stages: possible and probable Alzheimer’s disease. The new diagnostic vision for Alzheimer’s envisions revised criteria with a specific focus on the biological changes that are considered to be the cornerstone of this disease in our days – with the PET amyloid beta scans moving to the forefront of the diagnosis. After the onset of the first symptoms, the patients are under the epithet of mild cognitive impairment, until the period where the independent daily functioning is kept exclusively with the help. The diagnostic procedure and the biofluid and imaging data of subjects at pre-dementia stage are constantly advancing by the researchers in the field. However, the importance of the early and accurate diagnosis of Alzheimer’s disease all over the world stays unchanged as the only way to in time apply proper medical and psychosocial care, that is structured according to the individual patient’s symptoms. This is the way for the increasing of the life quality of the patients and their caregivers and also significantly reducing the overall social and medical cost.
3.1 Early Signs and Symptoms
Treatment for the early stages of Alzheimer’s will usually consist of pharmaceuticals, either singly or in combination, that help to maintain the proper balance of chemicals in the brain which improves communication among nerve cells and help to promote a general healthy function of the brain. An example of such medication is Exelon or Donepezil, which has been found to temporarily slow down the progression of some symptoms. Also, preventing or treating the diseases and conditions that result in dementia may help to reduce your risk of developing Alzheimer’s. For instance, regular exercise and a healthy diet is crucial in preventing diseases like hypertension, heart disease, and diabetes, which are all risk factors of developing Alzheimer’s.
In the early stages, the most noticeable symptom is memory loss. Specifically, individuals may have difficulty recalling things that happened recently or an ability to retain new information. As the disease progresses, the symptoms extend from simple forgetfulness to more profound memory loss and general mental decline. For instance, patients may become disoriented and have difficulty in recognizing their family members. They may also have difficulty in understanding a particular language, or performing activities such as dressing, playing, bathing, and eating. On the physical side, patients may have trouble writing, may shuffle while walking, or may experience a weakening of the muscles on one or both sides of the face. Also, they may have incontinence and complete dependence on the caregivers for their activities of daily living.
Alzheimer’s disease typically progresses slowly in three general stages – mild (early-stage), moderate (middle-stage), and severe (late-stage). Since Alzheimer’s affects people in different ways, the age in which the disease occurs, and the rate of progression can vary. On average, a person with Alzheimer’s lives four to eight years after diagnosis, but can live as long as 20 years, depending on other factors.
3.2 Diagnostic Criteria and Assessment Tools
Collectively, these tools and techniques allow healthcare professionals to make a thorough assessment of an individual’s cognitive function and to make a diagnosis of Alzheimer’s disease. Such a diagnosis can open up access to treatment and can allow those with the condition and their loved ones to access support and plan for the future.
Brain imaging can be used to identify any shrinking of the brain, which is associated with Alzheimer’s disease, or to rule out other possible causes of symptoms, such as a stroke. Memory testing, meanwhile, is used to help show how well a person’s memory works, compared to how well it should work for a person of their age and educational background. Neuropsychological tests are used to measure specific cognitive abilities, such as memory, attention, and problem-solving. These may be used in conjunction with one another and repeated at regular intervals in order to monitor changes in cognitive abilities over time.
In practice, a mixture of assessments is conducted to try to build up an overall picture of how a person’s memory and cognitive function has changed over time. These assessments might include brain imaging, blood tests, a full medical history, a thorough physical examination, memory testing, and other neuropsychological tests.
The most commonly used diagnostic criteria are those published by the National Institute on Aging (NIA) and the Alzheimer’s Association. These criteria require that there is a progressive decline in memory and other cognitive abilities, and that more than one cognitive domain is impaired. It is also necessary that a person’s symptoms are not better accounted for by another condition, and that they represent a significant decline from the person’s previous level of functioning.
In order to make a diagnosis of Alzheimer’s disease, healthcare professionals use a range of different criteria and assessment tools. These are designed to help doctors and specialists to identify the condition at an early stage, and to rule out other possible causes of the symptoms.
Diagnostic criteria and assessment tools
3.3 Differential Diagnosis
Importantly, it discusses the importance of differential diagnosis to differentiate Alzheimer’s disease from other conditions with similar symptoms. The clinical symptoms of Alzheimer’s disease are very similar to those of other types of dementia. For example, a common type of dementia is vascular dementia which occurs when the oxygen supply to the brain becomes reduced (often because of a series of small strokes) and can damage the memory and thought processes. As a certain degree of memory problems is common in people over 65 who do not have dementia, it is important to carefully assess any type of cognitive decline when it’s first noted. It is also important to diagnose a person with dementia as early as possible; in this way, they will get the right treatment and support at the right time. The information in this section will help to understand the different forms of dementia and Alzheimer’s disease, and it will help me to practice the importance of the person-centered approach to the person who has those conditions. Also, it will help the next of kin or main carers to understand the importance of that approach too. The medical research has advanced in preventing, slowing, and curing Alzheimer’s and related dementia. There are already medications and management strategies that are designed not only to manage symptoms, but to slow the progression of Alzheimer’s disease. However, these are yet to work for everyone, and the effectiveness can vary from one person to another, leading to the message that early diagnosis is important, as the earlier the diagnosis, the more effective the treatment and support might be. This will definitely improve people’s life and help them to preserve their mental abilities for an extended period of time. Also, they will have time to plan for the future. The medical practitioners can help by discussing the benefit of early diagnosis with their patient and their main carer or next of kin, and explaining the assessment process and the steps. However, the patient will have the right to withdraw the information sharing at any time during the diagnostic process. Also, a patient’s refusal for assessment needs to be fully respected and the patient should be reviewed if there are any concerns for changes in the condition. The legislation that covers the assessment, diagnosis and the rights of the patients and medical practitioners include the Mental Capacity Act 2005 and also specific legislative frameworks, such as the codes of practices in connection with the Mental Health Act 2007.
4. Management and Treatment Approaches
Alzheimer’s disease is a progressive illness. Over time, the symptoms become more severe as the damage to the brain becomes more extensive. While there is no cure, there are some medications and interventions that can improve the quality of life for those with Alzheimer’s. Some treatments, such as Huperzine A, Tramiprosate, and Ginkgo Biloba, also help memory and prevent the progression of cognitive decline; mostly, these are available without a prescription. While they may not work for everyone, research has shown that these treatments can benefit memory and cognition and reduce feelings of stress and anxiety. However, consult a physician before making any changes to your or your loved one’s treatment plan. These non-pharmacological treatments can be used in addition to a basic daily routine. They are designed to help manage the behavioral or mental symptoms of Alzheimer’s. For instance, a routine that includes some physical exhaustion and consistent meal and bedtimes could enhance the mood, limit distress, and help one rest better throughout the night. It is also important to encourage involvement in hands-on activity, such as music therapy. Patients with the disease are likely to have musical aptitude and a deep appreciation for music because the ability to recognize music is normally processed in the right hemisphere of the brain. Creative arts, such as drawing or painting, can also give individuals a sense of accomplishment and has been shown to decrease challenging behaviors. According to a recent study, improvement has been noticed in anxiety, depression, and appetite levels from art activities. Music and art activities can help the patients with expressing their emotions or thoughts; the ability to rely less on verbal and written communication as the disease progresses is, therefore, important. Alzheimer’s caregiving and management focus on maintaining the quality of life for the patient and helping the family to guide the patient to a better environment. The care might be done at home under the guidance of a home health care nurse, a nursing home with skilled professionals, or outside the traditional clinic setting provided by an adult health care center. Also, the care is usually personalized according to each individual’s needs and its benefits and effects. A focus of attention in Alzheimer’s patient management should be popularized to art and music as to promote well-being for individuals suffering from the disease and a strategy for minimizing the social burden. Furthermore, the environment nurturing these activities should be fostered, as research has proven that a non-pharmacological approach.
4.1 Pharmacological Interventions
A class of drugs called cholinesterase inhibitors (ChEIs) are generally used for the treatment of Alzheimer’s disease. ChEIs carry out their function by increasing the level of a particular chemical messenger in the brain called acetylcholine, which is involved in the mechanism of thinking, learning, and memory. By increasing acetylcholine levels, ChEIs can temporarily improve or stabilize the symptoms of Alzheimer’s. However, the results of prescribing ChEIs vary among individuals. Some might have significant improvement in cognitive functions and meaningful memory enhancement that allow them to continue with daily activities and tasks for months or even years. Some might only stabilize the symptoms with no additional benefit, while others might experience bad side effects and show no effective signs of the medication. This kind of medication is more commonly used for cases that are in the early to moderate stage of Alzheimer’s disease because the effectiveness of ChEIs will be lesser and minimal when the disease is in the severe stage. According to studies and practices, there are three types of ChEIs that have been considered and widely used: Donepezil, Galantamine, and Rivastigmine. The first drug approved by the U.S. Food and Drug Administration (FDA) for Alzheimer’s disease is Donepezil. However, Donepezil has been proven to cause less gastric irritation compared to Galantamine and Rivastigmine, which may induce stomach upset in patients. Besides, it has also been shown that Donepezil only needs to be taken once daily and the dosage is very simple, starting from 5mg to 10mg, while both Galantamine and Rivastigmine require two to three times consumption per day and the increase in dosage is more complicated and complex than Donepezil. On the other hand, there is another class of drugs called Memantine, which is recommended for people with moderate to severe Alzheimer’s disease. Memantine is able to normalize the activity of glutamate, which is another type of chemical messenger involved in brain functions such as learning and memory. As the disease progresses to the moderate and severe stage, the acceleration of the damage and loss of connections between nerve cells in the brain will increase. Hence, Memantine is prescribed to slow down the symptoms. Nowadays, some scientific research indicates that the combination of ChEIs and Memantine could provide better treatment for Alzheimer’s disease compared to using ChEIs or Memantine alone, even more significant results in the aspects of cognition and function. However, more detailed actual evidence and study data should be further investigated in the future. Last but not least, it is important to highlight that the response to medication, treatment, and side effects will vary among individuals. Hence, close monitoring of the patient’s condition and periodic consultations and reviews with doctors are essential to determine the optimal treatment. By targeting the helping group, another kind of medication called antidepressants is found effective in promoting significant improvement.
4.2 Non-Pharmacological Interventions
The final potential non-pharmacological treatment is music therapy. Listening to music does not require any cognitive assistance and could assist in reducing stress and enhancing general quality of life. As music is linked to emotional memories, patients use it as a coping technique to assist with their negative feelings, which is related to their illnesses and incapacity to express certain wishes. Just as evidence has shown, this is not a scientific intervention yet, and non-pharmacological strategies need to be encouraged in staying away from side effects of taking long-term medication, such as depression and lack of reward. It looks as if music acts as a beacon for emotions, and so far, music moves have made it a mission to create a world dementia-friendly community by spreading awareness of dementia and the positive impact music can make and promoting a free application named Ceilidh for Foghlam Alba. This is a digital learning platform in Scotland which provides practices of traditional music and is a communal map for individuals doing karaoke and enjoying musical activities. Such diverse strategies continue to develop the movement of enhancing dementia care. The importance of independence can be explained by a story and has proven the effectiveness of this music intervention. In May, information from BBC of an elderly woman’s singing shared by her caregiver to the world. In the true event, using music as a form of non-pharmacological intervention is not dismissive. This woman used to sing until her final stage of Alzheimer’s disease, and music had given her the voice and meaning to continue engaging in what she loved. The video has reached more than two million people worldwide, and it demonstrates the empowerment and success of such music intervention. However, as a future place, more research could be conducted in combining music with sensory breaking therapy, which can trigger the person’s vigilance to the fresh acoustic signal and to be involved in novel sensory experiences. It is expected to affect several cognitive functions as watching for acoustics could stimulate brain areas responsible for memory and attention and gradually increase alertness and response to treatment. With the most recent music present on both radio and television programs and that music is a global phenomenon, it will be easier for general patients living with Alzheimer’s disease to enjoy family and social support towards these readily accessible non-pharmacological interventions. Music will change the way of living and quality of life towards an individual and would positively reduce the burden of both family members and the society through infection of negative emotions and depression towards the illnesses. The authors linked an assigned music from emotional memories with a new semantic interpretation, which could have a positive approach to say that music preserved intact emotion and can invoke memory because music has a confidence effect on arousal and mood, and it can successfully modulate these functions against losses due to the nature of particular happenings from the medical experience. So far, the creators are convinced that this research and experimenting method can provide strong support for the potential music interventions in the early to moderate stage of Alzheimer’s disease. However, further investigations of coupling between voice transformation and medication activity would lead the potential and comparison studies to better trust these music effects for clinical application.
4.3 Supportive Care and Lifestyle Modifications
Supportive care for Alzheimer’s disease is important because the disease is progressive, and people with the disease need a lot of help. As the disease advances over time, more and more care and assistance is necessary. Most of the time, family members or friends provide this care. Caregiving can have positive aspects, but it is also common for caregivers to experience a great deal of stress. In fact, many caregivers suffer from depression and high levels of stress, which can be very harmful to their health. This is why it is so important for caregivers to be aware of and make use of support services. These services can provide family members with the information, the help, the professional advice, and the relief that they need to continue to provide the necessary care. There are medicines available which can help to slow down the process of the disease in the brain. Helping the person to stay active and to continue with enjoyable hobbies can be an important part of the care that they receive. Evidence suggests that activity and stimulation is beneficial for brain health. Alzheimer’s patients can become disoriented, confused and very forgetful. Providing the person with a familiar and structured environment helps to make sense of their world and can help the person to lead a more active and normal life for longer. Changes to the home environment can be a great help to both the person with Alzheimer’s and to those caring for them. For example, labels can be put on cupboards and drawers to help the person with memory problems find what they want. It’s also a good idea to make sure that anything that could be a danger to the person, such as medicine or cleaning products, is safely stored away. Routine tasks, like keeping down clutter and deciding where to keep things like the house keys, can help the person to keep an active role in their daily life. Cognitive stimulation therapy is a popular treatment for early to mid-stages of Alzheimer’s. This is a social treatment, and often takes place in groups where those in the early to mid-stages of the disease are encouraged to take part in activities and discussions, which are designed to improve their cognitive abilities, their social life, and their day-to-day living skills. Cognitive stimulation therapy has been shown to have good effect in some trials of large groups of patients.

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