Introduction
Alzheimer’s disease (AD) is one of the most common illnesses affecting large populations across the world. AD is a form of dementia accounting for 60% to 80% of all cases of dementia. Others in the dementia category include Lewy bodies, vascular dementia, mixed dementia, and frontotemporal dementia among others. Certain groups of people are more affected than others. In this paper, the focus will be on the definition of AD paying attention to the diagnosis, symptoms, prevalence, participating factors, and a description of more vulnerable groups. Additionally, common treatments will be outlined and, lastly, a theoretical framework for AD will be described.
Definition
Several definitions have been developed for AD. The disease has been described as both a progressive and incurable neurodegenerative illness whose prevalence rapidly increases with age and the lack of appropriate interventions (Wan et al., 2020; Mathys et al., 2019). Even with the multiple definitions, AD is yet to be fully understood because of its complexity and the aberrant interaction of multiple molecular pathways (Hampel, et al., 2018). After years of research, the term AD is associated with two distinct entities: AD neuropathologic changes and the prototypical syndromes absent from the neuropathologic verification (Jack et al., 2018). It is important to highlight that AD at autopsy is characterized by several elements, including intraneuronal neurofibrillary tangles and extracellular amyloid plaques. These components comprise microtubule-associated protein tau and misfolded and aggregated amyloid-beta peptide respectively (Wan et al., 2020; Egan et al., 2018)). AD often starts with a mild memory loss, which culminates into more severe impairments in the cognitive and executive functions (Mathys et al., 2019). Therefore, AD is a serious public health problem that is most commonly associated with aging.
The diagnosis of AD is often accomplished using the NIA-AA diagnostic criteria. The NIA-AA is an acronym for the National Institute on Aging-Alzheimer’s Association which was initially developed in 1984 and has since been revised to accommodate the several types and levels of AD (Weller & Budson, 2018). For example, the mild cognitive impairment (MCI) resulting from AD led to a 2011 modification of the NIA-AA. The pathology of AD allows the use of supportive biomarker evidence, including serum, CSF, and imaging. The biomarkers also help to distinguish AD from other types of dementia in addition to diagnosing the MCI resulting from AD. Another major clinical criterion for AD diagnosis is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (Weller & Budson, 2018). The DSM-5 helped re-classify dementia, delirium, and amnestic among other cognitive illnesses into broader neurocognitive disorders.
Experts recommend that AD should be diagnosed early enough to improve the chances and success of treatment. According to Liu et al. (2018), the future of AD treatment depends on early and accurate analysis. Today, several approaches, including functional and structural neuroimages such as positron emission tomotherapy (PET) and magnetic resonance imaging (MRI) have helped in the understanding of the functional and anatomical AD neural changes. The tools and approaches to diagnosis are still under development.
The symptoms of AD are another important aspect that should be carefully studied considering the complexity resulting from multiple forms, types, and levels of the disorder. As mentioned earlier, the major indicators of AD are memory loss which is initially a mild case. With no treatment, the AD culminates into more severe cognitive and executive impairments (Mathys et al., 2019). The MCI also transits from normal control (NC) to dementia. Liu et al. (2018) state that the MCI is usually the precursor of AD. CDC (2019) outlines other symptoms of AD such as impaired thinking and behavioral deterioration that adversely affects social life, work, and lifelong hobbies. However, a clinical diagnosis ascertains the presence of AD using the various biomarkers.
Genetics plays a key role in the development of AD. A study by Mielke (2018) finds that genetic variants such as the APOE genotypes, head trauma, pregnancy, and prostate cancer are the key precipitating factors. A detailed discussion of the genetic factors has been presented by the National Institute on Aging (2021) where genetic mutations are defined as permanent changes in one or several specific genes. This is the process in which cancers and tumors develop and the National Institute on Aging (2021) explains that genetic mutations are part of some of the early-onset of AD. The genes are inherited thus making AD a genetic risk factor. Additionally, individuals having a genetic variant of the APOE gene (apolitein E) have a higher risk of AD. This is because the APOE gene is involved in the production of a protein that aids in carrying fats and cholesterol in the bloodstream.
From a biological perspective, AD can be described using neurobiology. According to Mathys et al. (2019), AD involves neuron-glia interactions that devastate neuronal functions and causes an upregulation of the innate immune responses. The complexity of these changes, however, can be masked by the bulk-tissue level resolution. Neurodegeneration potentially causes changes in cell composition and activity in specified cell types. While the biological perspective explains the root causes of AD, the psychological point of view can potentially address the symptoms. For example, the cognitive and executive functions are psychological elements an impairment that indicates the presence of AD (Mathys et al., 2019). The emotions can be expressed when the quality of life among AD patients declines.
Emotional and psychological factors affecting AD have also been discussed in the literature. Emotions are often associated with the impacts of AD as opposed to being risk factors. Memory loss and declines in the quality of life can be associated with a negative emotions such as sadness. From a psychological point of view, there are several risk factors, including anxiety, sleep disturbance, and depression that are used as indicators of AD. Rather than contributing to AD, emotional and psychological factors have been described in studies such as Burke et al. (2018) as predictors of AD. From a psychological perspective, therefore, the symptoms of AD can be developed from the psychological and emotional status of an individual.
Treatment
The current treatment of AD involves several forms of pharmacologic therapy. Some of these include melamine, which acts both as a dopamine agonist and a non-competitive N-methyl-D-aspartate receptor antagonist, for moderate to severe AD patients (Weller & Budson, 2018). The second form entails the use of cholinesterase inhibitors, including donepezil, galantamine, and rivastigmine, for patients with mild, severe, or moderate AD. Besides these two classes, there are several options for those who prefer alternative therapy. Examples include nutraceutical huperzine A, which has proven beneficial for daily living activities and memory functions. Huperzine A is a government-approved intervention outside of the United States and is not currently regulated by the Food and Drug Administration (FDA) meaning that the purity and potency of the drug can fluctuate (Weller & Budson, 2018). Additionally, deficiency in vitamin D is a risk factor and, therefore, recommended for those patients diagnosed with this disorder.
Most of the common treatments involve the use of inhibitors and interventions for the various risk factors. The application of beta-site amyloid precursor protein cleaving enzyme 1 (BACE 1) is described by Coimbra et al. (2018). These researchers use the amyloid cascade hypothesis which states that the accumulation of the extracellular amyloid β (Aβ) is the critical molecular event in AD. Therefore, BACE 1 limits the rate of Aβ production thus effectively acting as an intervention for AD. In the management of risk factors, scholars such as Weller and Budson (2018) discuss the use of non-steroid anti-inflammatory drugs, which have not been scientifically proven, and omega-3 fatty acids, including fish oil. In the last decade, as explained by Weller and Budson (2018), these supplements have been observed to have cardiovascular benefits with two randomized control trials providing evidence that fish oil improved memory and thinking among MCI patients. The only limitation of these studies was the small sample used.
It is important to emphasize that cholinergic therapy is among the most popular interventions for AD, which also uses inhibitors. This treatment involves the restoration of the cholinergic function using compounds that work by blocking the enzymes which break down acetylcholine. The cholinesterase inhibitors also sustain the activity of acetylcholine at cholinergic synapses. Among the drugs approved by the FDA in this form of therapy include rivastigmine, donepezil, and galantamine. Statistics have shown that these drugs improve global and daily function, cognition, and other behavioral manifestations of AD. However, cholinergic interventions are still considered to be symptomatic treatments for AD.
Theoretical Framework
Several theories have been developed to describe AD since the disorder was first discovered. The aging theory is arguably one of the most prominent among them as discussed by multiple researchers (Trevisan et al., 2019). Aging has been defined by Liguori et al. (2018) as the process by which the human body loses the functioning of tissues and organs over time. One framework of aging is called free radical theory, which was later termed as the oxidative stress theory of aging (OSTA). It is founded on the hypothesis that functional losses associated with age are the result of accumulated oxidative damage to macromolecules such as proteins, lipids, and DNA by reactive oxygen and nitrogen species (RONS). AD is one of the age-related diseases and a neurodegenerative condition where brain tissue biopsies indicate low levels of MMP, p16, and IL-6 (Liguori et al., 2018). Therefore, AD and other forms of dementia can be explained using the OSTA.
The aging theory, in general, holds that aging is a random, time-dependent, and chronic-degenerative process subjected to all individuals. Both genetic and environmental factors play a critical role in aging. Different tissues and organs have different rates of aging in the individual since their use differs across lifestyles. The basic rule is that the more organs and tissues are used the more they age. Examples include the ligaments of a soccer player or other athletes in comparison with a normal non-athletic person. In the brain, however, aging and the use of tissues and organs are different because more formation of education has been associated with AD prevention (Trevisan et al., 2019). The aging of tissues reduces cell renewal, an activity that is not infinite. The brain, however, lacks mitotic capacity after differentiation.
Among the theories of aging, therefore, oxidative stress remains one of those that best explain AD. It is a complex process in which metal ions can bind with Aβ and get involved in the formation of reactive oxygen species (ROS). Oxidation often targets the neuronal membrane biomolecules leading to the impairment of the integrity of the membrane. Additionally, Aβ gets damaged during the production of ROS resulting in cell toxicity (Cheignon et al., 2018). One of the characteristics of AD is the reduction in brain volume and aging is the primary risk factor for this phenomenon. Besides reduction in brain volume, the presence of amyloid plaques and the resulting AD show that aging theory, in general, is a perfect explanation of the disorder.
With aging as the primary reason for AD, the interventions would seek not to reverse or prevent aging but to address the specific risk factors. According to Giudetti et al. (2018), the inflammatory and oxidative nature of AD and other neurodegenerative disorders mean that the therapeutic strategies under development seek to dampen the inflammation and oxidation processes. The fatty acids are effective in reversing memory loss and improving cognitive functioning. Therefore, an intervention such as palmitoylethanolamide (PEA) can be recommended. PEA is a fatty acid amide that belongs to the category of nuclear factor agonists and works by binding a nuclear receptor and exerting multiple biological functions. Additionally, PEA has anti-inflammatory, neuroreceptors, anticonvulsant, and antinociceptive properties that dampen reactive astrogliosis. The consumption of antioxidants and vitamins is another means of countering oxidative stress. This is because these products and supplements have anti-aging properties.
Application of Theory
The application of the aging theory to diverse populations is only possible across both genders but is confined to the elderly. The basic idea behind this framework is that aging diminishes cell replacement and other processes that result in AD. Among the elderly, the oxidative stress theory of aging presents both an explanation of how AD occurs and what interventions can work best. As discussed by Giudetti et al. (2018), the oxidative nature of AD means that the most effective interventions are that dampen the oxidation process. Among the elderly, there has not been much research regarding the differences in aging or oxidative stress across genders, race/ethnicity, religion, or sexual orientation. However, the theory can be used to explain the declining cognitive functioning in aging people due to declining brain volume. Anti-aging products such as antioxidants and vitamins, as per the oxidative stress theory of aging, can prevent the decline in brain volume among the elderly.
Conclusion
AD is one of the most common forms of dementia, especially among individuals of advanced ages. The literature review presented above defines the disease as a progressive and incurable neurodegenerative illness whose prevalence rapidly increases with age and the lack of appropriate interventions. It is noted, however, that multiple definitions have been offered as research into the disorder progresses. The symptoms and diagnosis of AD have been discussed in detail among other psychological, emotional, and biological aspects. The most common treatments have been shown to include managing the risk factors and the use of inhibitors. Lastly, the theoretical framework adopted for explaining AD is the theory of aging, specifically the oxidative stress theory of aging. AD, therefore, is a disease mostly associated with aging and which has adverse effects on the individuals’ quality of life.
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