Alzheimer’s Disease School Analisys
In contemporary society, the prevalence and incidence of Alzheimer’s disease (AD) and dementia continue to rise with population aging, owing to demographic gains, and changes in lifestyles. Among the most widespread types of dementia AD occupies a special place and represents a multifaceted ailment the mechanisms of which are still poorly understood. The more individuals dig into the nature of AD, the more questions are raised regarding the conceptual models of the disease. It might be sensible to utilize our existing awareness of the link between cardiovascular ailments, AD, and cerebrovascular illness to enhance efforts to delay or slow the progression of AD since there is no known cure or totally effective approach to avert the strains of the disease. Nonetheless, since there is a bulk of knowledge about the epidemiology, genetics, and pathophysiology of AD, various theoretical models associated with the ailment are developed in the hope of tackling the malady. There also exists a clear description of AD’s risk factors and ongoing research on the condition is conducted with the hope of a positive result.
In the 21st century, individuals aged 85 years and above represent the fastest-growing portion of the human population. This remarkable growth has brought various challenges for contemporary healthcare since senior citizens are regarded as being extremely vulnerable to ailments and disabilities. It has been observed that in every three adults, one person is suffering from AD or other types of dementia. The prevalence and incidence of this trend are expected to rise significantly over the ensuing 40 years unless preventive approaches are established and adequate measures are taken. AD contributes to the list of six largest leading causes of death in the US, registering significant costs for its research and treatment.
Each year billions of dollars are spent on AD in terms of care and caregiver’s lost incomes. People spend a lot on the disease which has no cure and virtually continues to affect them spiritually and financially, giving them a hefty burden. Irrespective of the global increase in the number of people with AD, it remains by far the only leading lethal condition that health experts and administrations are unable to cure or prevent. What makes it difficult to develop new treatments to slow the progression of the ailment is the outstanding heterogeneity of risk factors, and neuropathological, and etiologic processes connected to the disorder. Fortunately, numerous experimental cures are presently in development. These are aimed at the creation of theoretical and practical models on what approaches and mechanisms might be involved in treating the ailment more effectively. Additionally, the models are reinforced with the appropriate research and understanding of the newly discovered AD risk factors which are known to include hypertension, high cholesterol, diabetes mellitus as well as lifestyle and environmental risk factors among others.
Theoretical Models in AD
In healthcare, various theoretical models have been advanced concerning the causes of AD. Such models examine the mechanisms that might be involved in the acquisition of the disorder. Among the theories, three models that support particular kinds of nonpharmacological approaches can be distinguished. They are the unmet needs, behavioral learning, and ecological vulnerability approaches.
The unmet needs theoretical model seeks to examine the patient’s behavior in relation to sensory deprivation, loneliness, and boredom. This is an essential model for sensory stimulation, social contact, and activities that are considered suitable for the treatment of AD. The behavioral learning model aims at testing the mechanism through which a patient is caught up in the association between the backgrounds of behaviors and their outcomes. It has been found that the consequences might be reinforcing and as such, a behavior adjustment model might be needed. In the environmental susceptibility model, the driving mechanisms behind the loss of coping abilities are examined as an apparent symptom of developing specific dementia. It has been established that there exists an increased susceptibility to the surrounding environment and a reduced threshold at which stimuli affect behavior. This has been considered essential in AD management as surroundings with low stimulation, relaxation treatment, and massage have been proven important.
It has been established by a variety of studies that continued and increased application of pharmacological theoretical models may facilitate the creation of new drugs for AD (Klein, 2013). The two leading models founded on the glutamatergic and cholinergic hypotheses of AD are presently employed. Though the models help in identifying some of the recollection and memory impairment experienced during AD, they nonetheless fail to reproduce the disease’s pattern fully. The studies that have been conducted and which have employed a combined modeling approach, like the simultaneous application of various drugs with the objective of impairing numerous transmitters or diverse features of a single system, have established no or negligible collective effect. The theoretical approaches employing selective muscarinic-1 (M1) receptor blockers have proven to mimic the cholinergic system status in AD successfully (Klein, 2013). Such methods include the scopolamine model and the ketamine model. They are considered appropriate for the evaluation of drugs that fail to act directly on the cholinergic system. This observation has created an awareness of acetylcholine and glutamate involvement in the disease pathophysiology.
- The Scopolamine Model
The scopolamine approach owes its roots to the cholinergic hypothesis of AD and aging and has played a major role in its creation. Scopolamine was being widely applied in obstetrics from the start of the 20th century until the mid-fifties to induce amnesia and a twilight condition during delivery. It was further investigated in the sixties and seventies and became apparent that the areas with a high number of cholinergic afferents, like the hippocampus, were involved in memory procedures. It was established that acetylcholine esterase activity was reduced in AD by 1965 where in 1974 healthy young volunteers administered with scopolamine showed a memory profile akin to that detected in senior persons.
The scopolamine model is utilized in a cognitive study to research the clinical correlates with acetylcholine deficiency. It has similarly been employed in elderly patients with the goal of accelerating the diagnosis and slowing down the course of AD. Nonetheless; the model failed to forecast a cognitive decline in the subjects’ sensitivity.
- The Ketamine Concept
This approach is regarded as important in the management of AD. Usually, ketamine is commonly used in the field of schizophrenia study to provoke cognitive effects. It has been, however, observed that the functions affected by ketamine in a patient’s body are similar to those impacted in AD. This has been an essential theoretical model in evaluating the mechanisms surrounding the treatment and management of the disorder.
- Animal Models
It is apparent that there is no animal model that will ever comprehensively capture the intricate human range of cellular, molecular, and functional impairments as observed in human AD patients. This is despite the successful application of animal theoretical models showing great significance for the breakthroughs in human understanding of the pathophysiology of AD. Nevertheless, animal theories have proven essential in the discovery of causal links of AD-associated molecules and provide the chances for in vivo analyses of new intervention approaches.
- Amyloid Cascade Model (ACM)
Usually, a clear and substantial diagnosis of AD is achieved only after the death of a patient and an autopsy is conducted. AD is identified with the incidence of β-amyloid portions in the brain. The ACM represents a widespread contemporary theory explaining the development and growth of AD. The β-amyloid plaques are known to gather in the brain from short pieces of proteins regarded to as the β-amyloid peptides (Klein, 2013). This accumulation has the visual effect of a cascade that resembles the creation of neurofibrillary tangles from a protein commonly called tau. The stated changes result in the loss of connectivity between the neurons in the brain, their ultimate death, and progressive dementia.
- Moir’s Approach
The concept was created by Dr. Moir who noted that plaque formation is not the important occurrence of AD but a reaction to an infection. According to the model, various diverse categories of infections are involved in this process. However, it is not clearly proven or researched that the infection causes AD (Wood, 2017). In theory, the β-amyloid peptides arrive to assist after an infection takes control. Then the cascade begins that results years later in AD.
Research Investigating Early AD Detection
Research investigating AD started many years ago. Yet, at that time AD was regarded as dementia characterized by a universal cognitive impairment. By then, there was little distinction between the common types of dementia, unlike today. In those years, research usually referred to the condition as ‘senile dementia’ and comprised patients with diverse etiologies, including cortical Lewy body ailment, multi-infarct dementia, AD, and frontotemporal dementia (Korolev, 2014). As the study went on to examine the mental outline of AD in detail, it generally came to be accepted that the early impairment illustrates an amnesic condition that may advance gradually for several years before the damage in other mental areas, like semantic memory where the manifestations of AD are more obvious. The research into the profile of the initial memory loss in AD was founded on the acknowledgment that memory is not a unified concept and it is now accepted that various memory subtypes might be differentially affected in a range of disorder states. This was viewed as being a breakthrough in the field of AD research, particularly in the initial detection of the disease.
These significant studies have proven that the responsiveness system, like that of recollection, might be separated into diverse subsystems carrying out unified tasks that relate to other detailed systems. This notwithstanding, the role of emphasis is often seen as being a common and non-specific feature reflecting the performance of the past. The studies into the practical and bodily separability of the structures imply that consideration is undertaken by a linkage of bodily regions. As such, attention is now seen as being neither a function of the brain as a whole nor the property of a single center.
Clinical studies and observations of AD patients show that they regularly have a great challenge in undertaking daily tasks at a comparatively early stage of the disorder when formal testing of non-memory functions like visuospatial capabilities, praxis, and language reveal little or no impairment. Caregivers often describe the patients as being unable to focus, concentrate, easily distractible, and getting into a muddle when faced with tasks and duties that they could previously handle without effort (Korolev, 2014). These observations supported with research resulted in the speculation that such patients might have attentional deficits that come together with the serious challenges to common daily activities and that the deficits might be an early pointer of AD.
The advancement and improvement observed in neuroscience, specifically in dividing attentional processes into distinct functions like shifting attention, orienting, divided attention, response selection, and vigilance among others helped researchers in investigating attention in AD in a more systematic approach. This is accomplished by trying to separate a cognitive operation into its constituent parts. When aiming at early AD detection, various questions arise. Is the prevailing characterization of the neuropsychological profile of early AD as a pure amnesia is a precise one or is it invariably followed by a deficit of attention at the early stages? In case it is not, what then represents the relationship of attention shortfalls to other mental parts like dialectal, semantic recollection, and visuospatial tasks? Are entire kinds of attention impacted in AD or are a few preserved until later in disorder while others are disrupted early on? Another question as to what the attention deficits reflect regarding the neural systems that are impacted by the ailment process confronts scientists.
In the research investigating early AD detection, it took nearly three decades for diagnostic nomenclature to undergo a significant re-evaluation. The move towards the pre-symptomatic and pre-dementia phases of AD brought prevention and cure significantly nearer to each other than before. The context of AD research has improved to where it is no longer appropriate to justify the significance of prevention as the utmost treatment objective. After approximately two decades of study intended for AD prevention, there are a lot of studies in support of numerous proposed risks and safety measures.
Understanding the etiology of AD resulted in the research examining the clinical relevance of brain transformations. Pathologically, AD is associated with the deposition of amyloid and the gathering of lots of tangles in some regions of the brain (Korolev, 2014). These processes are distinguished to begin before the start of dementia. People with milder cognitive impairment and those with no cognitive signs at all are associated with AD-type brain transformations and changes. However, the research established that not all patients with AD-type brain changes will develop an obvious mental impairment. Additionally, less information is available regarding the time course of the accumulation of the identified brain changes until the start of clinical symptoms. Strong research needs pathological and cognitive facts while the patient is alive and it is just recently chosen features of AD pathology that have been identified in vivo over time. This is essential for the early detection of AD as the data and studies have so far primarily confirmed post-mortem information only.
AD: Risk Factors
Various recent studies on the ground of AD have detected numerous risk factors for cognitive failure. Protracted hypertension has been acknowledged as the key threatening factor for AD as it leads to condensing blood vessels, lessening their elasticity, and constricting the lumen predominantly in minor veins. As a result of these complications, there is reduced blood flow in the cerebrum which represents a key determinant of the pathophysiology of AD. Protracted hypertension has similarly been observed to cause a blood-brain barrier (BBB) integrity resulting in both the introduction of systemic components into the brain parenchyma and cerebral edema. The investigation into the hypertension risk factor has unearthed that it is related to smaller brain volumes in regions characteristically affected by AD such as the hippocampus. There is clear evidence that increased relaxing state and cardiac rate pressure product when used as a substitute for myocardial oxygen usage reveal inconsistent influence on neocortical amyloidosis in midlife persons with preclinical AD.
Epidemiological research has also indicated a great association between hypertension and dementia, making the former a risk factor though the relationship is intricate according to the research by the Alzheimer Society of Canada (2015) because the risk of AD and dementia might differ in direction and strength due to the age of onset. Various other studies have nonetheless shown that antihypertensive medications may lessen the risk of AD, which further complicates the findings. On the other hand, there is a lot of evidence emphasizing that hypertension in late years is closely related to an increased risk of AD.
In the central nervous system, cholesterol metabolism plays an essential part as the brain represents a cholesterol-rich organ having over 25% of the body’s store of the substance. According to another study, lipoprotein lipase which signifies a hydrolyzing enzyme could be involved in the genetic formation of AD through its modulation of cholesterol homeostasis in brain cells (Alzheimer Society of Canada, 2015). In cholesterol transport and catabolism of triglyceride-rich lipoprotein components, Apolipoprotein E becomes crucial. In the maintenance of synaptic plasticity and maturation of synapses, cholesterol supplied as a lipoprotein compound is vital as well. Besides, cholesterol levels have been observed to influence the creation of neurofibrillary tangles and clearance of Aβ through action at the lipid rafts placed in neuronal membranes.
A frequent outcome of increased cholesterol entails atherosclerosis and is an essential risk factor for AD. The research carried out by the Alzheimer Society of Canada (2015) revealed that comorbid AD is increasingly associated with patients with atherosclerosis. In some studies, raised aggregate serum cholesterol levels have been linked to AD risk while other investigations have established a complex relationship between cholesterol and AD. Similar to hypertension, it has been identified that the risk of dementia related to increased cholesterol might be impacted by the duration and severity of the disease as well as its treatment intensity. One justification that has been brought forward in connection to this intricacy is that plasma cholesterol intensities fail to reflect fat concentrations in the BBB. The relationship between the growing feasibility of AD occurrence and high cholesterol is described as close in several studies evaluating the theory that statins that participate in the reduction of cholesterol may prohibit the start or development of AD.
Diabetes mellitus (DM) represents an intricate metabolic condition that is closely connected with the changes in cognition and other factors causing dementia and cognitive declines like atherosclerosis and hypertension. DM is provoked by a lasting period of hyperglycemia or increased blood glucose levels. There are two kinds of DM type 1 is congenital and results from insulin deficiency and type 2 is inherited and caused by insulin resistance (Alzheimer Society of Canada, 2015). The accurate mechanism of the manner in which deficiency in insulin elevates the risk of AD remains unknown. This is despite the presence of a correlation between AD and the molecular mechanisms controlling diabetes.
The literature regarding diabetes mellitus as an AD risk factor is divided into two dissimilar schools of thought. One of them bases its facts on Rotterdam research outcomes implying that the excess of glucose or insulin from diabetes mellitus type brings about AD (Landau et al., 2010). This assertion is founded on the research demonstrating that AD patients have increasingly higher glucose and insulin levels compared to healthy people. The second school of thought states that the absolute insulin deficiency with a beta cell dysfunction as in full-blown diabetes type 2 may well stimulate AD by affecting insulin’s capability to undertake its functions in the brain.
Lifestyle, Environmental and Behavioral Risk Factors
Sedentary lifestyles and high-fat foods have led to a growing incidence of dyslipidemia, obesity, high blood pressure, and other disrupted metabolic conditions. The disorders come before and at times develop together with diabetes and atherosclerosis leading to AD. Major depression has similarly been associated with AD. More recently environmental exposures like pollution and fungal pathogens have been under study for their link to AD development. Thus, there is an extensive body of research that explores smoking, obesity, major depression, aerobic exercise, and exposure to air contamination and fungal pathogens as primary risk factors for acquiring AD.
Obesity has been on the rise in the contemporary world and is typically associated with changes in diets and lifestyles. The mechanism by which obesity increases AD and cognition risks remains under extensive investigation (Alzheimer Society of Canada, 2015). One of the possible ways might be through vascular pathologies or genetic, inflammatory, or hormonal processes at work. Various research into the subject has reported a marked impairment of cognitive ability in patients suffering from obesity compared to those whose weight remains within the required range. In the course of epidemiological research, it was discovered that there are vivid relationships between the increased AD risk in females and obesity (Tangney et al., 2011). Additionally, other studies have uncovered significant chances of developing dementia for both sexes. However, most researchers in the area agree that due to the uniqueness of each organism, the relationship differs from patient to patient. It has been established that the link between the body mass index (BMI) and the acquisition of AD appears to be stronger later in life. Obesity has therefore remained a widely accepted and vital independent risk factor for numerous health issues, including AD.
Aerobic Workout and Body Fitness
Alzheimer Society of Canada (2015) claims that a healthy way of life and aerobic exercises diminish the frequency of AD in comparison to having a passive life rhythm. With increased wealth and sedentary lifestyles among individuals and whole communities, cardiovascular conditions have become very common. Physical workout has always been seen to improve brain function, lower the chance of vascular diseases, and boost cognitive competencies. Through randomly managed tests and with as little as six months of training, such positive alterations as an increased hippocampal volume, enhanced spatial recollection and better performed main function tasks were recorded. Similarly, aerobic exercising enhances brain-delivered neurotrophic features which increase plasticity in the hippocampus.
The detailed study by Landau et al. (2010) of the connection between physical activity and the disease has revealed a reduced threat of dementia and mental decline. It has similarly been observed that in the participants undertaking aerobic exercise, the volume of gray and white matter in the brain grew. A recent meta-analysis of clinical tests regarding the intervention of exercise in patients who have dementia showed positive outcomes (Landau et al., 2010). The research into diabetic patients who undertake physical exercise proved substantial enhancement in cognitive function.
Heart rate variability (HRV) is connected to body fitness. The individuals exercising heavily are frequently recorded a high HRV. It is common knowledge that aging and the lack of physical exercise are linked to impaired cardiac vagal function which leads to a low HRV (Alzheimer Society of Canada, 2015). Vagal tone forms a significant portion of HRV and may be quantified through respiratory sinus arrhythmia (RSA). RSA is higher in older persons who exercise and thus show improved performance in tasks requiring verbal episodic memory which is a cognitive function that is impaired during the early years of AD.
Various studies have illustrated that long-term cigarette smoking represents a determinant of AD. Plasma homocysteine, whose capacity is exceedingly increased by smoking, signifies an aggravating factor for AD, mental deficiency, and other dementias (Rusanen, Kivipelto, Quesenberry, Zhou, & Whitmer, 2011). Smoking is also known to enhance atherosclerosis and may result in oxidative stress which is connected to excitotoxicity eventually resulting in neural death.
Late-onset depression has regularly been connected with AD and AD patients with instances of major depression during their lifetimes reveal enhanced hippocampal pathology at autopsy. Protracted and untreated major depressive condition is commonly associated with the selective impairment of noradrenergic cells in the locus coeruleus promoting AD.
A recent study by Rusanen et al. (2011) has identified fungal macromolecules as being a likely pathophysiological substrate of AD. The presence of mycological cells in numerous proportions and hyphae inside the blood vessels of some AD patients indicate that fungal infections could be found in the system and under favorable conditions provoke the pathology causing AD. The study conducted on AD patients showed that a peptide that manifests as a key promoter of AD pathology might wield antimicrobial action for numerous organisms indicating that a brain with AD might naturally induce Aβ-facilitated inflammatory activity against other conditions. Numerous types of spirochetes have also been linked with AD.
Chronic exposure to air contamination has largely been linked to a low HRV and represents another environmental factor related to AD. Most importantly, long-term exposure to high particulate matter in the air and high ozone levels result in the enhanced risk of metabolic syndromes and obesity among others. Air pollution posing a considerable risk to the array of various health disorders is a driving factor for developing AD as well.
In conclusion, the incidence and prevalence of AD continue to rise with the aging of the population leading to changes in life expectancy and the overall health rates of both the US and global population. The ailment is among the leading causes of death in the US. Significant amounts are spent yearly on patient care. In efforts to manage the disease, various theoretical models have been advanced. These models have been supported by adequate research which entails attempts to understand the AD’s primary risk factors. The models examine the mechanisms that may be involved in AD development. They study patient behavior in connection to loneliness, sensory deprivation, and boredom, examine the mechanism of the relationship between backgrounds of behaviors and the consequences, and analyze the principles behind the impairment of coping skills as a sign of developing dementia. They, together with plenty of other methods, are essential in the battle against AD.
Significant research has been conducted in attempts to uncover the etymology of AD. Years of scientific work have been dedicated to the study of AD’s basic symptoms. Although various questions remain unanswered in relation to AD early detection and effective treatment, much improvement has been made regarding the management of the disease. Such factors as chronic hypertension, high cholesterol, Diabetes mellitus, obesity, smoking, the lack of physical fitness, major depression, fungal pathogens, and air pollution among others have been identified as the determinants of the disease that can be combated and thus the chances for preventing the condition grow and give hope for a future positive outcome.