Alzheimer's disease

The Columbia Encyclopedia, 6th ed.

Alzheimer's disease

Alzheimer's disease (ăls´hī´mərz, ôls–), degenerative disease of nerve cells in the cerebral cortex that leads to atrophy of the brain and senile dementia and, ultimately, death. The disease is characterized by abnormal accumulation of plaques and by neurofibrillary tangles (malformed nerve cells), changes in brain tissue first described by Alois Alzheimer in 1906. The plaques result from the release and accumulation of excessive amounts of amyloid-beta (or beta-amyloid) proteins, normal proteins whose function in the body is not known. The neurofibrillary tangles prevent transportation of synthesized products within the cell body to organelles and target sites. The plaques and neurofibrillary tangles prevent proper transmission of electrochemical signals necessary for information processing and retrieval. The plaques also suffocate neurons by inhibiting proper blood supplies from reaching them.

Alzheimer's disease usually affects people over age 65, although it can appear in people as young as 40, especially in some familial forms of the disease. A condition called mild cognitive impairment, in which a person experiences an inability to form memories for events that occurred a few minutes ago, typically is the first sign of the disease. Although other conditions may cause mild cognitive impairment, if no identifiable cause is present, it leads to Alzheimer's in some 80% of the cases. As the disease progresses, a variety of symptoms may become apparent, including loss of memory, anxiety, confusion, irritability, and restlessness, as well as disorientation, impaired judgment and concentration, and more severe emotional and behavioral disorders. Alzheimer's patients ultimately become incapable of properly caring for themselves and communicating, and may become bedridden before dying from the physical effects of the disease (such as the inability to swallow). As an underlying cause of death, the disease is almost as significant as heart disease and cancer.

The cause of Alzheimer's is unknown, but a number of genes appear to be associated with the disease. Mutations in a gene on chromosome 21, which is also associated with Down syndrome, and another gene on chromosome 14 have been found in early-onset cases. Late-onset cases, which are the vast majority, may be caused by a combination of genetic and environmental factors. In 1999 scientists discovered an enzyme, named beta-secretase, that begins the process in the brain leading to Alzheimer's disease. One study has suggested that the buildup of amyloid-beta protein in some patients is due to slower than normal clearance of the protein from the brain.

There is as yet no known cure. Genetic screening for families with a history of early Alzheimer's is sometimes advised. Treatment includes relieving the patient's symptoms and alleviating stress on caregivers through support groups and counseling services. Donepezil (Aricept), rivastigmine (Exelon), and other acetylcholinesterase inhibitors provide temporary improvement for some patients with mild to moderate Alzheimer's. Memantine (Namenda), which appears to protect against damage from the effects of excess glutamate, slows the progression of the disease in some patients in the late stage of Alzheimer's.

See study by D. Shenk (2001).

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