Alzheimer disease

degenerative brain disorder that develops in mid to late adulthood. It results in a progressive and irreversible decline in memory and a deterioration of various other cognitive abilities. The disease is characterized by the destruction of nerve cells and neural connections in the cerebral cortex of the brain and by a significant loss of brain mass. The disease was first described in 1906 by Alois Alzheimer, a German neuropathologist.

Alzheimer disease is the most common form of *dementia. The disease develops differently among individuals; this suggests that more than one pathologic process may lead to the same outcome. Typically, the first symptom to appear is forgetfulness. As the disease progresses, memory loss becomes more severe, and language, perceptual, and motor skills deteriorate. Mood becomes unstable, and the individual tends to become irritable and more sensitive to stress and may become intermittently angry, anxious, or depressed. In advanced stages, the individual becomes unresponsive and loses mobility and control of body functions; death ensues after a disease course lasting from 2 to 20 years.

About 10 percent of those who develop the disease are younger than 60 years of age. These cases, referred to as early-onset familial Alzheimer disease, result from an inherited genetic mutation. The majority of cases of Alzheimer disease, however, develop after age 60 (late-onset); they usually occur sporadically—i.e., in individuals with no family history of the disease—although a genetic factor has been identified that is thought to predispose these individuals to the disorder.

The presence of neuritic plaques and neurofibrillary tangles in the brain are used to diagnose Alzheimer disease in autopsy. Neuritic plaques—also called senile, dendritic, or amyloid plaques—consist of deteriorating neuronal material surrounding deposits of a sticky protein called beta amyloid. This protein is derived from a larger molecule called amyloid precursor protein, which is a normal component of nerve cells. Neurofibrillary tangles are twisted protein fibres located within nerve cells. These fibres consist of a protein, called tau, that normally occurs in neurons. When incorrectly processed, tau molecules clump together and form tangles. Both neuritic plaques and neurofibrillary tangles, which also may be found in smaller amounts in the brains of healthy elderly persons, are thought to interfere in some way with normal cellular functioning. However, it is not known whether the plaques and tangles are a cause or a consequence of the disease.

Other features have been noted in the brains of many persons with Alzheimer disease. One is a deficiency of the neurotransmitter acetylcholine; neurons containing acetylcholine play an important role in memory. Abnormal concentrations of aluminum also have been found in neurofibrillary tangles and neuritic plaques, but it is not known whether the element plays a causative role in the disease.

Underlying genetic defects have been identified for both late- and early-onset cases of Alzheimer disease. A defect in the gene that codes for amyloid precursor protein may increase the production or deposition of beta amyloid, which forms the core of neuritic plaques. This gene, however, is responsible for only 2 to 3 percent of all early-onset cases of the disease; the remainder are attributed to two other genes. A defect in the gene that directs production of apolipoprotein E (ApoE), which is involved in cholesterol transport, may be a factor in the majority of late-onset Alzheimer cases. There are three forms of this gene—ApoE2, ApoE3, and ApoE4—one of which, ApoE4, is associated with a higher risk of disease.

There is no cure for Alzheimer disease. The medication tacrine slightly slows the progression of the disease by slowing the breakdown of acetylcholine, but it is not effective in all patients and can become toxic to the liver. Most treatment aims to control the depression, behavioral problems, and insomnia that often accompany the disease.

*dementia
chronic, usually progressive deterioration of intellectual capacity associated with the widespread loss of nerve cells and the shrinkage of brain tissue. Dementia is most commonly seen in the elderly (senile dementia), though it is not part of the normal aging process and can affect persons of any age.

The most common irreversible dementia is Alzheimer disease. This condition begins with memory loss, which may first appear to be simple absentmindedness or forgetfulness. As dementia progresses, the loss of memory broadens in scope until the individual can no longer remember basic social and survival skills or function independently. Language, spatial or temporal orientation, judgment, or other cognitive capacities may decline, and personality changes may also occur. Dementia is also present in other degenerative brain diseases including Pick disease and Parkinson disease.

The second most common cause of dementia is hypertension (high blood pressure) or other vascular conditions. This type of dementia, called multi-infarct, or vascular, dementia results from a series of small strokes that progressively destroy the brain. Dementia can also be caused by Huntington disease, syphilis, multiple sclerosis, acquired immune deficiency syndrome (AIDS), and some types of encephalitis. Treatable dementias occur in hypothyroidism, other metabolic diseases, and some malignant tumours. Treatment of the underlying disease in these cases may inhibit the progress of dementia but usually does not reverse it.