The Early Diagnosis of Alzheimer's Disease: From Behavioral to Genetic Study

The Early Diagnosis of Alzheimer's Disease: From Behavioral to Genetic Study

Yanna Ren, Weiping Yang, Xiaoyu Tang, Fengxia Wu, Satoshi Takahashi, Jinglong Wu
DOI: 10.4018/978-1-5225-0925-7.ch001
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Abstract

Alzheimer's disease, a common form of dementia, is a type of neurodegenerative disease that affects more than 30% of the population older than 85. Clinically, it is characterized as memory loss and cognitive decline. Pathologically, its symptoms include cerebral atrophy, amyloid plaques and NFTs. Generally, the life expectancy is no more than nine years after the definite diagnosis, and life expectancy exceeds 14 years in only 3% of patients. Presently, there is no effective treatment to stop the process; the only measures we can take are to ease or improve symptoms temporarily. Therefore, it is necessary to diagnosis the disease in the early stage, such as through imaging detection via CT, MRI, PET and MSR, or prediction before the disease (genetic examination). However, literature data have supported the notion that Alzheimer's disease patients show cognitive reserve abilities to some degree. In the future, research perspectives may focus on the cognitive training paradigms in compensatory and restorative strategies.
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Introduction

Alzheimer's disease (AD), also known as just Alzheimer's, is the sixth leading cause of death in the United States and is the fifth leading cause of death in Americans aged 65 or older (Association, 2011). Alzheimer’s disease, which is a chronic neurodegenerative disease, accounts for 60 to 70% of dementia cases. It often begins in people over 65 years of age and is an aging-related neurodegenerative disorder (Palop et al., 2003). According to Hebert, in next 40 years, the number of individuals with Alzheimer’s disease in the United States will increase dramatically (Hebert et al., 2013). There were approximately 4.5 million people with Alzheimer’s disease in 2000, and this number has since reached 5.1 million. This number is expected to reach 5.7 million by 2020, 7.7 million by 2030, 11.0 million by 2040, and 13.2 million by 2050 (Figure 1).

Figure 1.

Estimated number of people aged 65 and over with AD in the United States

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The exact causes that lead to Alzheimer’s disease are not yet known. However, many experts have now reached an agreement that, similar to other chronic diseases, Alzheimer’s disease likely develops as a result of multiple factors. Changes in the brain include the accumulation of the protein β amyloid outside of the neuron and the accumulation of the protein tau in the neuron (Hebert et al., 2013). In addition, approximately 70% of the risk is believed to be genetic, with many genes usually involved, such as apolipoprotein E- ɛ4 (APOE ɛ4). The APOE gene has three common forms, APOE ɛ2, APOE ɛ3 and APOE ɛ4; this gene provides a blueprint for one type of transmitter protein that carries cholesterol in the bloodstream. Every individual inherits one form from each of his or her parents. If an individual inherits APOE ɛ4, their risk of developing Alzheimer’s disease is increased. Moreover, those individuals have an increased risk of developing it at an earlier age than those who inherit the APOE ɛ2 or APOE ɛ3 genes from their parents. However, those who inherit two APOE ɛ4 genes have a higher risk. Other risk factors include a history of head injuries, depression, or hypertension (Hebert et al., 2013).

Clinically, in the early stage, the most common symptom is short-term memory problems, which mainly present as the inability to remember recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, not managing self-care, and behavioral issues. Generally, during long-term memory deficits, episodic memory is the most vulnerable, followed by semantic memory and, finally, procedural memory (Figure 2).

Figure 2.

The sequence of memory impairment in AD

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Pathologically, the main characteristics include the following: loss of neurons, neuritic plaques, granular-vacuolar degeneration, abundant amyloid plaques, neurofibrillary tangles (NFTs), and dystrophic neurites containing hyperphosphorylated tau. All of these neuropathological characteristics can be used as diagnostic markers of AD (Crews & Masliah, 2010).

No treatments stop or reverse the progression of AD, although some may temporarily improve symptoms. However, the present neuroscience investigations show that the cognitive deficits of Alzheimer’s disease can produce significant functional impairments. Although memory deficits are typically most prominent, impairments in attention, visuospatial functioning, language, reasoning, and executive functioning are common, along with personality changes and behavioral disturbances (Sitzer et al., 2006). The most important measure is early diagnosis and consequent intervention. Recently, with the development of investigative techniques for the diagnosis of Alzheimer’s disease, neuroimaging, biological markers and genetic examinations increase the probability of the early diagnosis of Alzheimer’s disease.

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