Alzheimer's Disease Health Article

Definition

Alzheimer's disease (AD) is the most common form of dementia, a neurologic disease characterized by a progressive loss of mental ability severe enough to interfere with normal activities of daily living, lasting at least six months, and not present from birth. AD usually occurs in old age and is marked by a decline in cognitive functions such as remembering, reasoning, and planning.

Description

A person with AD usually has a gradual decline in mental functions, often beginning with slight memory loss, followed by losses in the ability to maintain employment, to plan and execute familiar tasks, and to reason and exercise judgment. Communication ability, mood, and personality may also be affected. Most people who have AD die within eight years of their diagnosis, although that interval may be as short as one year or as long as 20 years. AD is the fourth leading cause of death in adults after heart disease, cancer, and stroke.

In 2001, four million Americans have been diagnosed with AD. That number is expected to grow to as many as 14 million by the middle of the twenty-first century as the baby-boomer population ages. These numbers may be seriously underestimated due to new research that suggests mild cognitive impairment may be early stages of AD.

While a small number of people in their 40s and 50s develop the disease (called early-onset AD), AD predominantly affects the elderly. AD affects about 10% of all people over the age of 65 and nearly half of those over85. Slightly more women than men are affected with AD, since women tend to live longer and occupy a larger proportion of the most affected age groups.

The costs for caring for loved ones with AD is considerable, and has been estimated at approximately $174,000 per person over the course of the disease. More than 70% of people with AD are cared for at home at an estimated annual cost of $196 billion. These costs are not supplemented by outside sources. If patients are cared for by paid home caregivers or are placed in nursing homes, the total annual out-of-pocket costs by families or third party payees account for $83 billion and $32 billion respectively.

Causes

The cause of Alzheimer's disease is unknown. Some strong leads have been found through recent research, however, and these have also given some theoretical support to several new experimental treatments.

AD affects brain cells responsible for learning, reasoning, and memory. Autopsies of people with AD indicate that these regions of the brain become clogged with two abnormal structures, neurofibrillary tangles and senile plaques. Neurofibrillary tangles are twisted masses of protein fibers inside nerve cells (neurons). Senile plaques are composed of parts of neurons surrounding a group of brain proteins called beta-amyloid deposits. While it is not clear exactly how these structures cause problems, some researchers now believe that their formation is responsible for the mental changes of AD, presumably by interfering with the normal communication between neurons in the brain. Drugs approved by the Food and Drug Administration (FDA) increase the level of chemical signaling molecules in the brain, known as neurotransmitters, to make up for this decreased communication ability.

What triggers the formation of plaques and tangles is unknown, although there are several possible candidates. Restriction of blood flow may be part of the problem, perhaps accounting for the beneficial effects of estrogen, which increases blood flow in the brain. However, studies in 2001 do not show estrogen as a protection against the development of AD.

Highly reactive molecular fragments called free radicals damage cells of all kinds, especially brain cells, which have smaller supplies of protective antioxidants thought to protect against free radical damage. Vitamin E is one such antioxidant, and its use in AD is showing some benefit.

Several genes have been implicated in AD, including the gene for amyloid precursor protein (APP) responsible for producing amyloid. Mutations in this gene are linked to some cases of the relatively uncommon earlyonset forms of AD. Other cases of early-onset AD are caused by mutations in the gene for another protein, presenilin. AD eventually affects nearly everyone with Down syndrome, caused by an extra copy of chromosome 21. Other mutations on other chromosomes have been linked to other early-onset cases.

Potentially the most important genetic link was discovered in the early 1990s on chromosome 19. A gene on this chromosome, apoE, codes for a protein involved in transporting lipids into neurons. ApoE occurs in at least three forms: apoE2, apoE3, and apoE4. Each person inherits one apoE from each parent, and therefore can either have one copy of two different forms or two copies of one. Compared to those without ApoE4, people with one copy are about three times as likely to develop lateonset AD, and those with two copies are almost four times as likely to do so. Despite this important link, not everyone with apoE4 develops AD, and people without it can still have the disease. Why apoE4 increases the chances of developing AD is not known.

Promising research in 2001 has discovered a protein, apoptosis-inducing factor, that kills cells by disrupting the genetic material at their cores. This discovery could lead to drugs that could turn off this protein that triggers apoptosis or biologically regulated cell death, which is important in fetal development but is also implicated in stroke, heart disease, and AD. It is thought that this protein runs out of control and shuts off otherwise healthy cells.

There are several risk factors that seem to increase a person's likelihood of developing the disease. The most significant one is, of course, age; older people develop AD at much higher rates than younger ones. Another risk factor is having a family history of AD, Down syndrome, or Parkinson's disease. People who have had head trauma or hypothyroidism may manifest the symptoms of AD sooner.

Many environmental factors have been suspected of contributing to AD, but population studies generally have not borne these out. A study in early 2001, however, showed a specific link between aluminum in drinking water and the incidence of AD. Other suspected risk factors were other pollutants in drinking water, aluminum in any form, and mercury in dental fillings. To date, none of these other factors has been shown to cause AD or to increase its likelihood.

Lifestyle factors, moreover, may prove to be better indicators of risk. Lack of stimulation, mentally and physically, between the ages of 20 and 60 seems linked to the incidence of AD. Studies have not shown, though, that a sedentary lifestyle early in life causes AD or whether it is a marker for the incidence of the disease.

Another study of African Americans and their Nigerian counterparts shows AD appearing more often in the American population than the African one. Researchers suggest that environmental or cultural factors may play a role in the formation of AD. Here, physical activity or diet may play a part.