Alzheimer’s disease [1]

Alternative names
Senile dementia/Alzheimer’s type (SDAT)

Definition

Alzheimer’s disease (AD), one form of dementia, is a progressive, degenerative brain disease. It impairs memory, thinking, and behavior.

Memory impairment is a necessary feature for the diagnosis of this or any type of dementia. Change in one of the following areas must also be present: language, decision-making ability, judgment, attention, and other areas of mental function and personality.

The rate of progression is different for each person. If AD develops rapidly, it is likely to continue to progress rapidly. If it has been slow to progress, it will likely continue on a slow course.

Causes, incidence, and risk factors

As many as 4 million Americans currently have AD. The older you get, the greater your risk of developing AD, although it is not a part of normal aging. Family history is another common risk factor.

In addition to age and family history, risk factors for AD may include:

     
  • Longstanding High blood pressure  
  • History of head trauma  
  • High levels of homocysteine (a body chemical that contributes to chronic illnesses such as heart disease, Depression, and possibly AD)  
  • Female gender - because women usually live longer than men, they are more likely to develop AD

There are two types of AD - early onset and late onset. In early onset AD, symptoms first appear before age 60. Early onset AD is much less common, accounting for only 5-10% of cases. However, it tends to progress rapidly.

The cause of AD is not entirely known but is thought to include both genetic and environmental factors. A diagnosis of AD is made based on characteristic symptoms and by excluding other causes of dementia.

Prior theories regarding the accumulation of aluminum, lead, mercury, and other substances in the brain leading to AD have been disproved. The only way to know for certain that someone had AD is by microscopic examination of a sample of brain tissue after death.

The brain tissue shows “neurofibrillary tangles” (twisted fragments of protein within nerve cells that clog up the cell), “neuritic plaques” (abnormal clusters of dead and dying nerve cells, other brain cells, and protein), and “senile plaques” (areas where products of dying nerve cells have accumulated around protein). Although these changes occur to some extent in all brains with age, there are many more of them in the brains of people with AD.

The destruction of nerve cells (neurons) leads to a decrease in neurotransmitters (substances secreted by a neuron to send a message to another neuron). The correct balance of neurotransmitters is critical to the brain.

By causing both structural and chemical problems in the brain, AD appears to disconnect areas of the brain that normally work together.

About 10 percent of all people over 70 have significant memory problems and about half of those are due to AD. The number of people with AD doubles each decade past age 70. Having a close blood relative who developed AD increases your risk.

Early onset disease can run in families and involves autosomal dominant, inherited mutations that may be the cause of the disease. So far, three early onset genes have been identified.

Late onset AD, the most common form of the disease, develops in people 60 and older and is thought to be less likely to occur in families. Late onset AD may run in some families, but the role of genes is less direct and definitive. These genes may not cause the problem itself, but simply increase the likelihood of formation of plaques and tangles or other AD-related pathologies in the brain.

Symptoms
In the early stages, the symptoms of AD may be subtle and resemble signs that people mistakenly attribute to “natural aging.” Symptoms often include:

     
  • Repeating statements  
  • Misplacing items  
  • Having trouble finding names for familiar objects  
  • Getting lost on familiar routes  
  • Personality changes  
  • Losing interest in things previously enjoyed  
  • Difficulty performing tasks that take some thought, but used to come easily, like balancing a checkbook, playing complex games (such as bridge), and learning new information or routines

In a more advanced stage, symptoms are more obvious:

     
  • Forgetting details about current events  
  • Forgetting events in your own life history, losing awareness of who you are  
  • Problems choosing proper clothing  
  • Hallucinations, arguments, striking out, and violent behavior  
  • Delusions, Depression, agitation  
  • Difficulty performing basic tasks like preparing meals and driving

At end stages of AD, a person can no longer survive without assistance. Most people in this stage no longer:

     
  • Understand language  
  • Recognize family members  
  • Perform basic activities of daily living such as eating, dressing, and bathing

Signs and tests
The first step in diagnosing Alzheimer’s disease is to establish that dementia is present. Then, the type of dementia should be clarified. A health care provider will take a history, do a physical exam (including a neurological exam), and perform a mental status examination.

Tests may be ordered to help determine if there is a treatable condition that could be causing dementia or contributing to the confusion of AD. These conditions include thyroid disease, vitamin deficiency, brain tumor, drug and medication intoxication, chronic infection, anemia, and severe depression.

AD usually has a characteristic pattern of symptoms and can be diagnosed by history and physical exam by an experienced clinician. Tests that are often done to evaluate or exclude other causes of dementia include computed tomography (CT), Magnetic Resonance Imaging (MRI), and blood tests.

In the early stages of dementia, brain image scans may be normal. In later stages, an MRI may show a decrease in the size of the cortex of the brain or of the area of the brain responsible for memory (the hippocampus). While the scans do not confirm the diagnosis of AD, they do exclude other causes of dementia (such as Stroke and tumor).

Treatment

Unfortunately, there is no cure for AD. The goals in treating AD are to:

     
  • Slow the progression of the disease.  
  • Manage behavior problems, confusion, and agitation.  
  • Modify the home enviroment.  
  • Support family members and other caregivers.

The most promising treatments include lifestyle changes, medications, and antioxidant supplements like vitamin E and ginkgo biloba.

LIFESTYLE CHANGES

The following steps can help people with AD:

     
  • Walk regularly with a caregiver or other reliable companion. This can improve communication skills and prevent wandering.  
  • Use bright light therapy to reduce Insomnia and wandering.  
  • Listen to calming music. This may reduce wandering and restlessness, boost brain chemicals, ease anxiety, enhance sleep, and improve behavior.  
  • Get a pet dog.  
  • Practice relaxation techniques.  
  • Receive regular massages. This is relaxing and provides social interactions.

DRUG TREATMENT

Several drugs are available to try to slow the progression of AD and possibly improve the person’s mental capabilities. These include donepezil (Aricept), rivastigmine (Exelon), galantamine (Reminyl), and tacrine (Cognex).

All of these drugs affect the level of acetylcholine (a neurotransmitter) in the brain and all have potential side effects, such as nausea and Vomiting. Tacrine also causes an elevation in liver enzymes and must be taken four times a day. It is now seldom used.

Aricept is taken once a day and may stabilize or even improve the person’s mental capabilities. It is generally well tolerated. Exelon, a new drug, shows a similar effectiveness and is taken twice a day.

Other medications may be required to control aggressive, agitated, or dangerous behaviors. These are usually given in very low doses, with adjustment as needed.

It may be necessary to stop any medications that worsen confusion. These may include pain killers, cimetidine, central nervous system depressants, antihistamines, sleeping pills, and others. Medications MUST NOT be stopped or changed without discussion with and direction from your doctor.

SUPPLEMENTS

Folate (Vitamin B9) is critical to the health of the nervous system. Together with some other B vitamins, folate is also responsible for clearing homocysteine (a body chemical that contributes to chronic illnesses) from the blood. High levels of homocysteine and low levels of both folate and Vitamin B12 have been found in people with AD. Although the benefits of taking these B vitamins for AD is not entirely clear, it may be worth considering them, particularly if your homocysteine levels are high.

Antioxidant supplements, like ginkgo biloba and vitamin E, scavange free radicals. These products of metabolism are highly reactive and can damage cells throughout the body.

Vitamin E dissolves in fat, readily enters the brain, and may slow down cell damage. In at least one well-designed study of people with AD who were followed for 2 years, those who took Vitamin E supplements had improvemed symptoms compared to those who took a placebo pill.

Ginkgo biloba is an herb widely used in Europe for treating dementia. It improves blood flow in the brain and contains flavonoids (plant substances) that act as antioxidants. Although many of the studies to date have been somewhat flawed, the idea that ginkgo may improve thinking, learning, and memory in those with AD has been promising. DO NOT use ginkgo if you take blood-thinning medications like warfarin (Coumadin) or a class of antidepressants called monoamine oxidase inhibitors (MAOIs).

If you are considering any drugs or supplements, you MUST talk to your doctor first. Remember that herbs and supplements available over the counter are NOT regulated by the FDA.

SUPPORT AT HOME

Someone with AD will need support in the home as the disease worsens. Family members or other caregivers can help by trying to understand how the person with AD perceives his or her world. Simplify the patient’s surroundings. Give frequent reminders, notes, lists of routine tasks, or directions for daily activities. Give the person with AD a chance to talk about their challenges and participate in their own care.

OTHER PRACTICAL STEPS

The person with AD should have hearing and sight evaluated. If deficits are found, he or she should be assisted by hearing aids, glasses, and cataract surgery as appropriate.

Those with AD may have particular dietary requirements, such as:

     
  • Extra calories due to increased physical activity from restlessness and wandering.  
  • Supervised meals and help with feeding. People with AD often forget to eat and drink, and can become dehydrated as a result.

The Safe Return Program, implemented by the Alzheimer’s Association, requires that a person with AD wear in identification bracelet. If he or she wanders, the caregiver can contact the police and the national Safe Return office, where information about the person is stored and shared nationwide.

Eventually, 24-hour monitoring and assistance may be necessary to provide a safe environment, control aggressive or agitated behavior, and meet physiologic needs. This may include in-home care, nursing homes, or adult day care.

Support Groups

For additional information and resources for people with Alzheimer’s disease and their caregivers, see Alzheimer’s disease support groups.

Expectations (prognosis)
The probable outcome is poor. The disorder is usually progresses steadily. Total disability is common. Death normally occurs within 15 years, usually from an infection or a failure of other body systems.

Complications

     
  • Loss of ability to function or care for self  
  • Bedsores, muscle contractures (loss of ability to move joints because of loss of muscle function), infection (particularly urinary tract infections and Pneumonia), and other complications related to immobility during end-stages of AD  
  • Falls and broken bones  
  • Loss of ability to interact  
  • Malnutrition and dehydration  
  • Failure of body systems  
  • Reduced life span  
  • Harmful or violent behavior toward self or others  
  • Abuse by an over-stressed caregiver  
  • Side effects of medications

Calling your health care provider

Call your health care provider if someone close to you experiences symptoms of senile dementia/Alzheimer’s type.

Call your health care provider if a person with this disorder experiences a sudden change in mental status. (A rapid change may indicate other illness.)

Discuss the situation with your health care provider if you are caring for a person with this disorder and the condition deteriorates to the point where you can no longer care for the person in your home.

Prevention

Although there is no proven way to prevent AD, there are some practices that may be worth incorporating into your daily routine, particularly if you have a family history of dementia. Talk to your doctor about any of these approaches, especially those that involve taking a medication or supplement.

     
  • Consume a low-fat diet.  
  • Eat cold-water fish (like tuna, salmon, and mackerel) rich in omega-3 fatty acids, at least 2 to 3 times per week.  
  • Reduce your intake of linoleic acid found in margarine, butter, and dairy products.  
  • Increase antioxidants like carotenoids, Vitamin E, and vitamin C by eating plenty of darkly colored fruits and vegetables.  
  • Maintain a normal blood pressure.  
  • Stay mentally and socially active throughout your life.  
  • Consider taking non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin), sulindac (Clinoril), or indomethacin (Indocin). Statin drugs, a class of medications normally used for High Cholesterol, may help lower your risk of AD. Talk to your doctor about the pros and cons of using these medications for prevention.

In addition, early testing of a vaccine against AD is underway.

Johns Hopkins patient information

Last revised: December 5, 2012
by Potos A. Aagen, M.D.

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