Neuropsychological and Genetic Factors in Alzheimer's Disease

Introduction

Alzheimer's disease is a debilitating illness that interferes with an individual's ability to recall both short-term and long-term memory. People diagnosed with the disease can initially recall recent activities, though they have difficulties with long-term memory. However, as the disease develops over time, patients experience difficulties with both short- and long-term memory. Given the increase in the number of people diagnosed with this condition, Alzheimer's disease is regarded as the most common type of dementia among the elderly. This clinical condition is caused by neurodegeneration and is characterized by a progressive decline in mental ability as well as difficulties in independent living. This paper examines the neuropsychological and genetic factors surrounding the illness, the early signs of the disease, and possible approaches to treatment.

Brief History of Alzheimer's Disease

Alzheimer's disease has a history that can be traced back over 100 years, to when Alois Alzheimer, a German physician, conducted a postmortem analysis of one of his patients' dementia-ravaged brains. When conducting this analysis, Alzheimer hoped to expose the biological roots of the patient's rapid and severe mental deterioration and unusual mood swings (Marsa, 2015, p. 54). The patient was surrounded by a fog of confusion, displayed delusional behavior, and would occasionally become wild and uncontrollable. During the examination, Alzheimer noticed that small clumps of hard bundles of protein — known as amyloid plaques — were clustered next to the labyrinthine circuitry of healthy nerve cells. Moreover, many fibers extending from the healthy nerve cells were not only tangled but also thickened. The main characteristic features of Alzheimer's disease are therefore these amyloid plaques and tau tangles in the brain circuitry. Since then, scientists and physicians have focused on identifying how these proteins function and what role they play in aberrant brain circuitry.

Since its discovery, Alzheimer's disease has become a major public health issue and is considered one of the most common forms of dementia across the globe, as it is a progressive neurodegenerative disease that affects many people, especially the elderly. The disease affects more than 20% of people aged 80 years and above and is estimated to affect more than 35 million people worldwide by 2050 (Femminella, Ferrara & Rengo, 2015, p. 1). As a result of this projection, Alzheimer's disease is increasingly likely to generate a significant economic and social burden.

Genetic Factors Surrounding Alzheimer's Disease

The causes of Alzheimer's disease are not yet fully understood by scientists, though increasing study of the disease shows that genes play a significant role in its development. Alzheimer's disease is an example of an inherited genetic illness, which is sometimes caused by a genetic mutation — a permanent change in certain genes. If an individual inherits a genetic mutation that causes Alzheimer's disease from a parent, he or she is increasingly likely to develop the disease. However, the disease may also be caused by the occurrence of a genetic variant, particularly when the variant increases disease risk or directly causes the disorder.

Prior to the era of gene identification, several clinical observations demonstrated that Alzheimer's disease has a genetic component. One of these observations is family history, which is regarded as a major risk factor for the disease. In addition to age, family history is the only risk factor that has been consistently recognized in epidemiological studies. The existence of an affected first-degree relative is linked with an estimated fourfold increased risk for Alzheimer's disease (Levy-Lahad & Bird, 1996, p. 829). According to the findings of several studies, the lifetime risk for first-degree relatives was close to 50%. This indicates that genes with autosomal dominant inheritance are major risk factors for a significant portion of Alzheimer's disease cases.

The second clinical observation linking the disease to a genetic component is that Alzheimer's disease and dementia are closely associated with Down syndrome (trisomy 21). Individuals with Down syndrome invariably develop the neuropathological attributes of Alzheimer's disease by age 40, implying that they have an enhanced incidence of clinical dementia. This in turn implicates chromosome 21 genes in the pathogenesis of Alzheimer's disease. The third observation is that in some families, the disease segregates as an autosomal dominant characteristic across several generations. This observation contributed to the hypothesis that a single gene mutation could be sufficient to generate Alzheimer's disease similar to that seen in the general population. Therefore, the genes responsible for familial Alzheimer's disease are seemingly relevant to those responsible for non-familial types as well.

Since Alzheimer's disease is a progressive and irreversible brain disorder, its genetic factors involve the development of amyloid plaques and neurofibrillary tangles. These factors contribute to the loss of connections between nerve cells and the eventual death of those cells in the brain circuitry. Generally, there are two kinds of Alzheimer's disease with varying genetic components: early-onset and late-onset. The causative genes of both types include amyloid precursor protein, apolipoprotein E, STM-2/PS-2, and the S182/PS-1 gene on chromosome 14 (Levy-Lahad & Bird, 1996, p. 829).

Early-onset Alzheimer's disease affects individuals between 30 and 60 years of age and represents less than 5% of Alzheimer's patients ("Alzheimer's Disease Genetics Fact Sheet," 2015). Some cases of early-onset Alzheimer's disease are caused by unknown factors, but most are inherited and are known as familial Alzheimer's disease. This type of the disease is caused by different single-gene mutations on chromosomes 1, 14, and 21. Each of these single-gene mutations results in the formation of abnormal proteins, which become causes of the disease. Gene mutations on chromosome 21 result in the creation of abnormal amyloid precursor protein, those on chromosome 14 generate abnormal presenilin 1, and mutations on chromosome 1 contribute to abnormal presenilin 2. Scientists have stated that each of these single-gene mutations plays a part in the breakdown of APP, a protein whose exact function is currently unknown. The breakdown of this protein is part of a process that creates harmful forms of amyloid plaques — a major factor in the development of Alzheimer's disease.

Late-onset Alzheimer's disease is the most common type and develops from age 60 onward. While its causes are not yet fully understood, it is commonly attributed to genetic, lifestyle, and environmental factors that increase an individual's risk of developing the disease. The single-gene mutations responsible for early-onset Alzheimer's disease do not appear to be involved in the late-onset form. Clinical researchers and scientists have not yet identified a single gene that definitively causes late-onset Alzheimer's disease. Nonetheless, one genetic risk factor — the apolipoprotein E gene found on chromosome 19 — is known to increase an individual's risk. Recent genome-wide screening technologies indicate that apolipoprotein E is the single most significant genetic risk factor in late-onset Alzheimer's disease (Bertram & Tanzi, 2012, p. 87). The most common form implicated as a major risk factor is APOE ε4. Apart from APOE ε4, researchers have found that BIN1, CR1, CLU, and PICALM are additional genes that increase an individual's risk of developing late-onset Alzheimer's disease.

Neuropsychological Factors Surrounding Alzheimer's Disease

Neuropsychological factors surrounding Alzheimer's disease are related to the concept of cognitive reserve, which has been suggested to account for the disconnection between the extent of brain damage or pathology and its clinical symptoms (Sobral, Pestana & Paul, 2015, p. 39). There are two kinds of reserve that reportedly generate independent and interactive contributions to preserving function following brain injury. Cognitive reserve refers to the ability of an individual to flexibly and efficiently use available brain resources. This concept has been widely used to inform our understanding of cognitive aging and to describe the ability of the adult brain to cope with the impact of neurodegenerative processes.

Individuals with a lower brain capacity — characterized by a smaller head circumference — have a higher risk of developing Alzheimer's disease. However, individuals with a higher cognitive reserve, operationalized by more years of education, have a lower risk (Tucker & Stern, 2011, p. 355). Cognitive reserve plays an important role in an individual's risk of developing Alzheimer's disease because it enables a person to compensate for pathology through better use of available brain resources. Based on the cognitive reserve model, people with higher reserve have effectively compensated for pathology in the early stages of the disease.

Cognitive reserve is not fixed; it continues to develop and evolve across the lifespan because of variables associated with lifetime experience. Some of these variables — including occupational achievement, education, and leisure activities — play an important role in maintaining cognitive function in old age. According to the findings of epidemiological studies, these lifetime experiences can increase reserve and contribute to a reduced risk of Alzheimer's disease. A significant portion of patients with Alzheimer's disease progress slowly, which indicates a constant need to identify factors that may slow the disease's development. Some clinical studies indicate faster rates of progression of Alzheimer's disease in patients with high cognitive reserve after the point of diagnosis.

Based on the findings of one study, there is a link between the degree of cognitive reserve and the stage of dementia, including Alzheimer's disease (Sobral, Pestana & Paul, 2015, p. 484). In this case, the level of cognitive reserve has a considerable impact on the progression of dementia. High levels of cognitive reserve, education, and significantly complex work all affected the rate of cognitive decline in individuals with Alzheimer's disease. Therefore, high levels of cognitive reserve and healthy lifestyles among older adults should be promoted in order to foster lifetime cognitive stimulation.

Conclusion

Alzheimer's disease is one of the most common forms of dementia that affects many people across the globe, especially the elderly. This disease has a history that dates back more than 100 years to when it was first described by a German physician. Alzheimer's disease is a progressive neurodegenerative disorder characterized by physical, cognitive, and behavioral impairment. There are two types of Alzheimer's disease — early-onset and late-onset — associated with varying genetic components. The disease is generally caused by the development of neurofibrillary tangles and amyloid plaques in the brain circuitry. The increased spread and severity of the condition has contributed to the development of several treatment approaches. The most commonly used modalities to improve recall include pharmacological medications and non-pharmacological therapies.

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