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Glossary
Alzheimer's Disease (AD)
 

Alzheimer's Disease (AD) is a form of dementia, which is a medical condition that disrupts the way the brain works, causing progressive decline in intellectual functioning severe enough to interfere with a person's daily life activities and social relationships. AD is named after the German neurologist, Alois Alzheimer [1864-1915], who first studied the disease. It is also sometimes called senile dementia of the Alzheimer type (SDAT).

AD is defined by the presence of specific anatomic abnormalities in the brain, called amyloid plaques and neurofibrillary tangles. These can only be detected by direct examination of brain tissue, which means that Alzheimer's disease is only diagnosed after death, via autopsy. In a living patient, doctors diagnose "probable AD" if a patient shows all the behavioral symptoms of AD, and if all other possible causes of dementia are ruled out.

AD accounts for more than 50% of all cases of dementia. The most common form of Alzheimer's occurs in people older than 65 years, but there is also a form called early-onset Alzheimer's disease or presenile dementia which can begin as early as age 40. A recent study estimated that about 4% of Americans between the ages of 65-74 have AD, and the rate grows steadily with age until about 50% of Americans over age 85 may have the disease.

Symptoms of Alzheimer's Disease

Alzheimer's disease is progressive, meaning that symptoms get worse as the disease progresses. The earliest recognized symptoms of Alzheimer's disease are often mild memory loss; a sufferer may begin to forget recent conversations or what year it is. There may be disorientation (e.g. getting lost in familiar surroundings), problems with routine tasks (like using a microwave), and changes in personality and judgment.

As the disease progresses, patients begin to have difficulty with the activities of daily living, and may require help feeding and bathing. There may be anxiety (suspiciousness and agitation), sleep disturbance, wandering and pacing, difficulty recognizing family and friends.

In the most advanced stages of the disease, patients suffer loss of the ability to speak, weight loss, lack of appetite, and loss of bowel and bladder control. By this point, patients require round-the-clock caregiving.

While AD itself is not directly fatal, it may leave patients vulnerable to infections and other diseases such as pneumonia, which may become the ultimate cause of death. Often, patients with the disease suffer increasing debilitation over a period of about 4-8 years, but an otherwise healthy individual can survive for decades.

Anatomical Changes in the Brain

Alzheimer's disease is characterized by anatomical changes, including the development of amyloid plaques and neurofibrillary tangles.

Amyloid plaques are sticky buildup which accumulates outside the nerve cells in the brain. Amyloid is a protein which is normally found throughout the body. In AD this protein begins to divide improperly, creating a substance called beta amyloid which is toxic to brain cells. As the beta amyloid builds up, the brain cells begin to die.

Neurofibrillary tangles are the second anatomical hallmark of AD. Normally, every brain cell contains long fibers made of protein which act as scaffolds, holding the brain cell in its proper shape and also helping transport of nutrients within the cell. In AD, these fibers begin to twist and tangle. The brain cell loses its shape and also becomes unable to transport nutrients properly; it eventually dies.

As enough plaques and tangles accumulate in the brain, widespread cell death occurs throughout the brain. At this point, it is unclear exactly why plaques and tangles begin to form in the brain of a person with AD. Many researchers are studying this question and trying to develop ways to halt or reverse the degeneration.

The plaques and tangles characteristic of Alzheimer's can be observed only through biopsy, which is usually done during an autopsy. This means that a doctor can only diagnose "probable" Alzheimer's in a living patient based on the pattern of behavioral symptoms, and by ruling out other possible causes. The firm diagnosis of Alzheimer's is made or ruled out after death.

A recent report announced the discovery of a vaccine that may hold promise for preventing or treating AD. The study considered mice who had been specifically bred to develop AD-like plaques in their brains. Young mice given the vaccine showed little or no development of plaques as they aged. When older mice, who had already developed plaques, were given the vaccine, the plaques appeared to dissolve.

This vaccine is causing tremendous excitement among those who study AD, since it suggests it might be possible to develop a way to immunize people against AD or reduce AD in those who already suffer the disease. However, it is important to remember that the rats in this study did not have AD: they were bred to develop plaques, but they did not develop neurofibrillary tangles. Some researchers suspect that the tangles, rather than the plaques, are the culprits that cause most of the damage in AD. Worse, not every person who dies of AD has plaques in his brain. Thus, a vaccine that fights plaques may not be enough to prevent or cure AD. It will take years of further study in animals to answer some of these questions, and years more before a human treatment becomes available. Nonetheless, this study is an example of the progress that is being made in understanding the various components of AD.

Possible Causes of Alzheimer's Disease

Several possible causes have been implicated in the development of AD. About 10% of patients with AD have the early-onset form of the disease, in which symptoms can appear as early as the 30s and 40s. Scientists have discovered that many people with this form of the disease have a specific genetic abnormality: mutation in genes located on chromosomes 1, 14, and 21. However, the correlation isn't perfect; people with these genetic abnormalities account for only 50% of all known cases of early-onset AD.

The more common form of AD is late-onset AD, in which symptoms begin to appear only late in life. This form of AD is also linked to a genetic abnormality. Chromosome 19 contains a gene called apoE which helps carry cholesterol in the blood and also helps nerves to recover after injury. Each of us has two copies of apoE - one inherited from each parent - and each copy can come in one of several forms: apoE2, apoE3, and apoE4. ApoE3 is the most common in the general population. But people who inherit one apoE4 gene have an increased risk of developing AD, and people who inherit two copies of apoE4 are about eight times as likely to develop AD as people with two copies of the "normal" apoE3 variant. Interestingly, the rarest apoE2 form of the gene may lower an individual's risk of AD.

A simple blood test is available to determine which forms of apoE a person has. However, this test cannot tell you whether or not you will develop AD, or when. Over half of the people who develop late-onset AD do not have the apoE4 gene, and not everyone with apoE4 does develop the disease. Right now, the blood test is most useful as a research tool, helping scientists study AD risk factors in large groups of people. Most scientists and health professionals do not recommend routine apoE4 tests for predicting AD risk in individuals, although it may be useful as part of a medical evaluation of a patient who already shows AD symptoms.

In addition to genetic factors, many biological factors have been implicated in AD. One of the best-studied is overproduction of free radicals, substances formed when the body metabolizes oxygen. Normally, free radicals serve important functions, such as helping the immune system fight off disease. However, too many free radicals can start to cause problems. Brain cells producing the mutated form of amyloid protein - the beta amyloid that forms the plaques in AD - seem to produce more free radicals. At this point, it's unclear whether free radicals boost beta amyloid production or vice versa.

There are also several environmental factors which have been suspected of contributing to AD risk. One of the earliest suspects was aluminum, which is a common contaminant in drinking water. Both the plaques and tangles in AD contain illuminum, and early studies linked AD with aluminum ingested through drinking water or even by using aluminum cooking utensils. However, most researchers are currently not convinced that there is a strong link between aluminum and AD.

Other environmental suspects which have been suggested to promote AD include zinc (normally found in shellfish, beans and dark turkey meat), smoking, high exposure to paint solvents, and exposure to electromagnetic fields (EMFs), the high-electricity areas around power lines and electrical machinery. People who have experienced head injuries or strokes may also be more prone to develop AD. Viral infections, such as HIV (the virus that causes AIDS), may also leave the brain vulnerable to AD.

Neither toxin ingestion, nor brain injury, nor viral infection alone is enough to cause AD. However, in people genetically predisposed to AD, these environmental factors may help trigger the disease or cause symptoms to appear earlier. Currently, much more research is needed to identify other triggering factors, to determine just how much they increase risk, and to learn what can be done to offset this risk.

Drugs to Treat Alzheimer's Disease

The search for a treatment or cure for Alzheimer's disease is one of the hottest fields in medical research. Several pharmaceutical companies are in the final stages of developing new drugs which may be ready for widespread trials soon. Before a drug can be sold in this country, it must undergo trials with thousands of people to determine whether the drug produces the effects its makers claim without unacceptable side effects. The average drug can take $300,000,000 and 12-25 years to develop and test before it can reach the market, and only a fraction of drugs make it this far.

At present, the only Alzheimer's drugs with FDA approval in this country are cholinergic drugs such as tacrine (brand name Cognex), donepezil (brand name Aricept), rivastigmine (brand name Exelon) and galantamine (brand name Reminyl). In AD, neuron death is worse in some areas of the brain than others. The learning and memory centers in the medial temporal lobes are particularly susceptible to damage, as are a small group of cells known as the basal forebrain, which produce a chemical called acetylcholine that is important for learning. When these cells die, brain levels of acetylcholine fall. The cholinergic drugs help to keep brain acetylcholine levels from falling too far. So far, these drugs have had only limited success in halting the progress of AD. Tacrine also causes severe side effects, so it is seldom prescribed today.

Cholinergic drugs are not the only class of drug under study. Other researchers are investigating other avenues: developing drugs which affect other brain chemicals, or which interfere with the formation of plaques and tangles in AD, or which bolster the brain's ability to grow new neurons to replace the ones killed off by the disease. These approaches hold some promise, and at this point several new drugs are in clinical trials to determine whether they produce reliable long-term effects. As with any kind of medicine, the advertising claims often outstrip the scientific proof. People who try new drugs and supplements which have not yet received FDA approval, or who participate in clinical trials, may be among the first to receive the benefits of a miraculous new medicine. But they should also be aware that some of these substances may have harmful long-term effects which have not yet been discovered.

There is also some limited evidence that dietary supplements can help fight or prevent AD. Some of the damage in AD is attributed to free radicals; compounds called anti-oxidants which fight free radical damage are found in vitamin C and vitamin E and in beta carotene (associated with vitamin A). There is some evidence that vitamin C or vitamin E supplements can slow down the course of AD over several years. Other anti-oxidants, such as gingko biloba and phosphatidylserine (abbreviated PS) are also marketed as AD treatments, though there is less evidence as yet to support this claim. Supplements containing high doses of anti-oxidants can cause severe side effects including internal bleeding - and can even be toxic in individuals taking anticoagulant medication. No one should take these or any supplements without consulting a doctor first.

A much safer way to consume anti-oxidants is as part of a healthy diet. Anti-oxidants are plentiful in fruits and vegetables (especially blueberries and yellow fruits and vegetables), in brown rice and whole grains, and in meats, eggs and dairy products. Caffeine is also an anti-oxidant.

Anti-inflammatory drugs, such as aspirin and NSAID painkillers (ibuprofen, naproxen sodium, etc.) reduce inflammation in the brain. There is some limited evidence that people who regularly take NSAIDs over an extended period (e.g for arthritis) have a lower incidence of AD and, if they do develop AD, show a slower rate of mental decline. There is less evidence that aspirin is effective against AD. NSAIDs have potentially serious side effects; some 100,000 Americans are hospitalized annually for NSAID-induced ulcers, and over 16,000 die. So, currently, doctors don't prescribe NSAIDs for AD protection alone. Researchers are working to develop a new kind of NSAID which protects the brain without causing such severe side effects.

Further Reading:

Article : "7-MINUTE SCREEN TEST"

Article : "CROSSING THE LINE"

Article : "ESTROGEN AND ALZHEIMER'S"

Article : "PUTTING GINGKO TO THE TEST"

Article : "NEW ALZHEIMER'S DRUG HELPS CAREGIVERS, TOO"

Article : "UNMASKING ALZHEIMER'S"

Article : "THE COLOR OF RISK"

Article : "CARING FOR CULTURE"

Article : "MINORITY REPORT "

Article: PUMPING NEURONS: EXERCISE TO MAINTAIN A HEALTHY BRIAN

 

by Catherine E. Myers. Copyright © 2006 Memory Loss and the Brain