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Alzheimer's disease (AD) is the most common neurodegenerative disorder projected to afflict more than 13 million Americans and 81 million individuals worldwide in the next 40 to 50 years. The disease is characterized by progressive cognitive and behavioral deficits accompanied by diffuse structural abnormalities in the brain. AD is associated with significant morbidity and mortality and is currently among the 10 most common causes of death in the United States. Unfortunately, the devastations of AD affect both the patient and caregivers, and involve numerous aspects of human life including physical, socioeconomic, psychological, functional, and quality of life. In addition, caring for patients with AD places heavy financial burden on patients, families, and the health care system at large. In the United States, the average annual cost of managing a patient with AD varies between $18,400 and $36,000, while, as a nation, we spend close to $100 billion each year to care for patients with AD. Similar data are reported from other countries as well. In the United Kingdom, more than $8 billion or 0.6% of the gross domestic product is spent each year to care for patients with cognitive impairments. Recognizing the enormity of the burden of AD, international collaborations between clinicians, researchers, policy makers, patient advocacy groups, the media, and many others have increased public awareness of the global impact of the disease and have laid the foundation for the development of effective preventive and therapeutic strategies as well as improvements in care management for patients with AD.
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Recent advances in biomedical research have provided critical knowledge related to the pathobiology of AD and mechanisms underlying neuronal plasticity and death. While current therapies work mainly to slow the inevitable progression of the disease, these newly identified mechanisms now serve as targets to develop effective novel therapies that could either delay or preferably arrest the progression of AD. Moreover, treatment strategies are being developed for primary prevention of AD, especially for individuals at increased risk for the disease. The present chapter includes information on the major aspects of AD, including the pathology, epidemiology, clinical presentations, diagnosis, management, and potential neuroprotective therapies. Details related to non-Alzheimer types of dementia are discussed in Chapter 67.
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Alzheimer's disease is characterized by progressive cognitive and behavioral deficits accompanied by diffuse structural abnormalities in the brain. The common symptoms of the disease include memory loss, confusion, impaired judgment, personality changes, disorientation, and loss of language skills. Based on the onset of symptoms, AD is normally divided into two groups: early- (<60 years) and late-onset (>60 years). Early-onset, also called familial AD (FAD), accounts for approximately 3% of all the cases and has to date been linked to mutations in the genes for the amyloid precursor protein (APP; gene name APP) on chromosome 21, presenilin 1 (PS1; gene name PSEN1) on chromosome 14, and presenilin 2 (PS2; gene name PSEN2) on chromosome 1. Among these genes, more than 160 different mutations have so far been identified, ...