Alzheimer's Disease

Alzheimer's disease (AD) is a progressive, degenerative brain disease that impairs memory, thinking, and behavior. AD, named after Alois Alzheimer, a German neurologist who published his observations of a patient, Augusta, D., in 1906, is the most common form of dementia, comprising 60% of all dementias. AD has been previously known as dementia of the Alzheimer type, senile dementia of the Alzheimer type, and Alzheimer's dementia.

AD currently affects about 4.5 million men and women in the United States, with an annual cost of $100 billion, and the number of persons with AD is expected to rise to 16 million by the year 2050. The incidence of AD increases with age, affecting up to 50% of people above the age of 85, although rare in those below the age of 60. There are other forms of dementia not related to AD, such as dementia with Lewy bodies (20%), vascular dementia (15%), and rare forms such as frontal-temporal dementia (5%) with women at greater risk for AD than vascular dementia. There is no known cause of AD, although it appears likely that a combination of factors, including age, genetic inheritance, environmental factors, diet, and overall general health, is responsible.

Although the first symptoms of AD are often confused with the changes that take place in normal aging, AD is not a normal part of aging and is caused by brain pathology. The brain of an affected individual may begin to deteriorate as much as 10 to 20 years before any visible signs or symptoms of AD appear. Typical symptoms of the early stages of AD may be attributed to many causes, making initial diagnosis difficult; they include memory loss, behavioral symptoms, emotional changes, and changes in judgment and decision making.

Over time, AD progresses through three main stages: mild, moderate, and severe. Memory impairment is a necessary feature for the diagnosis of AD or any type of dementia. Change in one of the following areas must also be present: language, decisionmaking ability, judgment, attention, and/or other areas of mental function and personality. The rate of progression is different for each person. If AD develops rapidly in an individual, it is likely to continue to progress rapidly. If it has been slow to progress, it will likely continue on a slow course.

Generally, the onset of AD is insidious, with failure of memory of recent events, emotional changes, depression, anxiety, and unpredictable behaviors being the earliest symptoms, appearing up to 3 years prior to diagnosis. Functional and behavioral problems may be evident and may increase anytime within 1.5 to 6 years after diagnosis, followed by progressive apathy, space perception disorders, a shuffling gait, slow and awkward movements, jerky muscle contractions (myoclonus), and irreversible loss of speech and memory. AD eventually progresses to a late vegetative phase consisting of complete inability to think, move, or speak. The patient usually dies of pneumonia, heart attack, or stroke.

While clinical symptoms and a thorough examination resulting in a diagnosis of probable AD are highly correlated with postmortem examination, a definitive diagnosis is made only after a postmortem examination. Postmortem examination of an AD patient will reveal a loss of cells in all cortical layers except the motor cortex and a degeneration of neurofibrils, the filaments found in and around nerve cells. Neurofibrillary degeneration and plaques, composed of amyloid protein, are distinctive histopathological features of the cerebral cortex in AD. The amyloid deposition is thought to be due to an abnormality in the amyloid precursor protein. This abnormality is influenced by several factors, including higher levels of stress hormones and the four alleles of the apolipoprotein E (APOE) genotype.

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