Definisi Alzheimer's and the Cause- Alzheimer's disease (AD) is a concept in evolution; it is considered by most to be a degenerative brain disease that was first described in 1906 and is the most common cause of dementia. Over the past 100 years, we have learned that many biological and clinical phenomena are included under the rubric of Alzheimer's disease and that perhaps the term can best be considered a two-word eponym that reveals as much about our ignorance as about our knowledge.
AD is characterized clinically by the insidious onset of cognitive difficulties, most commonly in memory and attention, that subsequently progress to involve language, perception, praxis, and (frequently) behavioral and psychological symptoms. Neuropathologically, the condition is characterized by progressive loss of neurons in association with neurofibrillary tangles and senile plaques. The cause of AD is unknown, although a variety of genetic mutations can cause early onset of AD and genetic susceptibility factors that modify late-onset disease have been identified. Much attention has focused on early recognition of AD, and a variety of labels, such as the controversial concept of mild cognitive impairment (MCI), have been used to label people who have mild intellectual difficulty. However, these terms are used primarily in research and should not be used clinically.
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AD is said to be the most common dementia worldwide, followed by vascular dementia and a variety of other neurodegenerative diseases such as Lewy body dementia and frontal lobe dementia. However, precise figures for incidence and prevalence are difficult to determine globally because of the differences in diagnostic criteria and assessment methodologies used in different countries.
Genetics and Causes of Dementia
Familial AD has been described for more than 50 years. The association of plaques and tangles developing late in life in individuals with trisomy 21 or Down syndrome implicated this chromosome in the genetics of early-onset autosomal dominant disease. Numerous mutations have been described in chromosome 21 as well as in chromosomes 1 and 14, all of which appear to alter amyloid processing. Although a variety of claims have been made for other susceptibility loci, the only well-confirmed risk factor for late-onset disease is apolipoprotein ∊4, produced by a gene on chromosome 19. Apolipoprotein ∊is a cholesterol transport protein hat exists in three forms: 2, 3, and 4. Individuals who have one or two copies of the apolipoprotein ∊4 form are more at risk for AD and some other diseases. The relationships between these genetic abnormalities and other pathological processes in AD are unclear.
Most of the focus has been on the potential damaging role of amyloid. However, cells may die because of inflammatory processes or other mechanisms such as excess excitation due to neurotransmitters (e.g., glutamate). The major risk factor for AD is age, and the relationship between normal aging changes in the brain and AD is controversial. Despite decades of intensive research, there are no biological markers that can clearly differentiate AD from normal aging.
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