What is dementia?

Dementia is a syndrome characterized by:

1. impairment in memory,

2. impairment in another area of thinking such as the ability to organize thoughts and reason, the ability to
use language, or the ability to see accurately the visual world (not because of eye disease), and

3. these impairments are severe enough to cause a decline in the patient's usual level of functioning.

Although some kinds of memory loss are normal parts of aging, the changes due to aging are not severe enough
to interfere with the level of function. Many different diseases can cause dementia, but Alzheimer's disease is by
far the most common cause for dementia in the United States and in most countries in the world.

What is Alzheimer's disease?

Alzheimer's disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of
memory and eventually by disturbances in reasoning, planning, language, and perception. Many scientists believe
that Alzheimer's disease results from an increase in the production or accumulation of a specific protein (beta-
amyloid protein) in the brain that leads to nerve cell death.

The likelihood of having Alzheimer's disease increases substantially after the age of 70 and may affect around
50% of persons over the age of 85. Nonetheless, Alzheimer's disease is not a normal part of aging and is not
something that inevitably happens in later life. For example, many people live to over 100 years of age and never
develop Alzheimer's disease.

Who develops Alzheimer's disease?

The main risk factor for Alzheimer's disease is increased age. As a population ages, the frequency of Alzheimer's
disease continues to increase. Ten percent of people over 65 years of age and 50% of those over 85 years of age
have Alzheimer's disease. Unless new treatments are developed to decrease the likelihood of developing
Alzheimer's disease, the number of individuals with Alzheimer's disease in the United States is expected to be 14
million by the year 2050.

There are also genetic risk factors for Alzheimer's disease. Most patients develop Alzheimer's disease after age
70. However, 2%-5% of patients develop the disease in the fourth or fifth decade of life (40s or 50s). At least half
of these early onset patients have inherited gene mutations associated with their Alzheimer's disease. Moreover,
the children of a patient with early onset Alzheimer's disease who has one of these gene mutations has a 50%
risk of developing Alzheimer's disease.

There is also a genetic risk for late onset cases. A relatively common form of a gene located on chromosome 19
is associated with late onset Alzheimer's disease. In the majority of Alzheimer's disease cases, however, no
specific genetic risks have yet been identified.

Other risk factors for Alzheimer's disease include high blood pressure (hypertension), coronary artery disease,
diabetes, and possibly elevated blood cholesterol. Individuals who have completed less than eight years of
education also have an increased risk for Alzheimer's disease. These factors increase the risk of Alzheimer's
disease, but by no means do they mean that Alzheimer's disease is inevitable in persons with these factors.

All patients with Down syndrome will develop the brain changes of Alzheimer's disease by 40 years of age. This
fact was also a clue to the "amyloid hypothesis of Alzheimer's disease" (see section later in this article).
What are the symptoms of Alzheimer's disease?

The onset of Alzheimer's disease is usually gradual, and it is slowly progressive. Memory problems that family
members initially dismiss as "a normal part of aging" are in retrospect noted by the family to be the first stages of
Alzheimer's disease. When memory and other problems with thinking start to consistently affect the usual level of
functioning; families begin to suspect that something more than "normal aging" is going on.

Problems of memory, particularly for recent events (short-term memory) are common early in the course of
Alzheimer's disease. For example, the individual may, on repeated occasions, forget to turn off an iron or fail to
recall which of the morning's medicines were taken. Mild personality changes, such as less spontaneity, apathy,
and a tendency to withdraw from social interactions, may occur early in the illness.

As the disease progresses, problems in abstract thinking and in other intellectual functions develop. The person
may begin to have trouble with figures when working on bills, with understanding what is being read, or with
organizing the day's work. Further disturbances in behavior and appearance may also be seen at this point, such
as agitation, irritability, quarrelsomeness, and a diminishing ability to dress appropriately.

Later in the course of the disorder, affected individuals may become confused or disoriented about what month or
year it is, be unable to describe accurately where they live, or be unable to name a place being visited.
Eventually, patients may wander, be unable to engage in conversation, erratic in mood, uncooperative, and lose
bladder and bowel control. In late stages of the disease, persons may become totally incapable of caring for
themselves. Death can then follow, perhaps from pneumonia or some other problem that occurs in severely
deteriorated states of health. Those who develop the disorder later in life more often die from other illnesses (such
as heart disease) rather than as a consequence of Alzheimer's disease.

Ten warning signs of Alzheimer's disease

The Alzheimer's Association has developed the following list of warning signs that include common symptoms of
Alzheimer's disease. Individuals who exhibit several of these symptoms should see a physician for a complete
evaluation.

1. Memory loss

2. Difficulty performing familiar tasks

3. Problems with language

4. Disorientation to time and place

5. Poor or decreased judgment

6. Problems with abstract thinking

7. Misplacing things

8. Changes in mood or behavior

9. Changes in personality

10. Loss of initiative

It is normal for certain kinds of memory, such as the ability to remember lists of words, to decline with normal
aging. In fact, normal individuals 50 years of age will recall only about 60% as many items on some kinds of
memory tests as individuals 20 years of age. Furthermore, everyone forgets, and every 20 year old is well aware
of multiple times he or she couldn't think of an answer on a test that he or she once knew. Almost no 20 year old
worries when he/she forgets something, that he/she has the 'early stages of Alzheimer's disease,' whereas an
individual 50 or 60 years of age with a few memory lapses may worry that they have the 'early stages of
Alzheimer's disease.'
Mild cognitive impairment

The criteria for dementia are conservative meaning that a patient must have had considerable decline in the
ability to think before a diagnosis of dementia is appropriate. The progression of Alzheimer's disease is so
insidious and slow that patients go through a period of decline where their memory is clearly worse than its
baseline, yet they still do not meet criteria for dementia. This transitional syndrome is called Mild Cognitive
Impairment (MCI). Individuals affected with MCI have cognitive impairment that is demonstrated on formal
neuropsychological testing but are still able to function well. Formal neuropsychological testing usually means that
the patient is administered a battery of standardized tests of memory and thinking. Some of these tests are
something like the IQ tests we may have taken in school. When these tests were developed they were
administered to hundreds or thousands of people so that statistics are available to say how a person's score
compares to a sample of healthy persons of the same age. If a person scores in the top 50%, it means that he or
she did better than at least 50% of other normal people who took the test. Persons with lower scores - often in the
bottom 7% - are considered to have MCI.

There are several forms of MCI. Perhaps the most common is associated with impairment in memory but not in
the ability to plan and reason. Persons with this type called "amnestic MCI" (amnestic comes from "amnesia" and
means no memory) have a high risk of developing Alzheimer's disease over the next few years. Persons with
preserved memory but impaired reasoning or impaired judgment (call non-amnestic MCI) have a lower risk of
developing Alzheimer's disease.

As treatments are developed that decrease the risk of developing Alzheimer's disease or slow its rate of
progression (as of June 2007, no such medication has been approved by the FDA), recognition of amnestic MCI
will be increasingly important. It is hoped that medications will be developed that will slow the rate of progression
of MCI to Alzheimer's disease or completely prevent the development of Alzheimer's disease.

What are causes of Alzheimer's disease?

The cause(s) of Alzheimer's disease is (are) not known. The "amyloid cascade hypothesis" is the most widely
discussed and researched hypothesis about the cause of Alzheimer's disease. The strongest data supporting the
amyloid cascade hypothesis comes from the study of early-onset inherited (genetic) Alzheimer's disease.
Mutations associated with Alzheimer's disease have been found in about half of the patients with early-onset
disease. In all of these patients, the mutation leads to excess production in the brain of a specific form of a small
protein fragment called ABeta (Aβ). Many scientists believe that in the majority of sporadic (for example, non-
inherited) cases of Alzheimer's disease (these make up the vast majority of all cases of Alzheimer's disease)
there is too little removal of this Aβ protein rather than too much production. In any case, much of the research in
finding ways to prevent or slow down Alzheimer's disease has focused on ways to decrease the amount of Aβ in
the brain.

What are risk factors for Alzheimer's disease?

The biggest risk factor for Alzheimer's disease is increased age. The likelihood of developing Alzheimer's disease
doubles every 5.5 years from 65 to 85 years of age. Whereas only 1%-2% of individuals 70 years of age have
Alzheimer's disease, in some studies around 40% of individuals 85 years of age have Alzheimer's disease.
Nonetheless, at least half of people who live past the 95 years of age do not have Alzheimer's disease.

Common forms of certain genes increase the risk of developing Alzheimer's disease, but do not invariably cause
Alzheimer's disease. The best-studied "risk" gene is the one that encodes apolipoprotein E (apoE). The apoE
gene has three different forms (alleles) -- apoE2, apoE3, and apoE4. The apoE4 form of the gene has been
associated with increased risk of Alzheimer's disease in most (but not all) populations studied. The frequency of
the apoE4 version of the gene in the general population varies, but is always less than 30% and frequently 8%-
15%. Persons with one copy of the E4 gene usually have about a two to three fold increased risk of developing
Alzheimer's disease. Persons with two copies of the E4 gene (usually around 1% of the population) have about a
nine-fold increase in risk. Nonetheless, even persons with two copies of the E4 gene don't always get Alzheimer's
disease. At least one copy of the E4 gene is found in 40% of patients with sporadic or late-onset Alzheimer's
disease.

This means that in majority of patients with Alzheimer's disease, no genetic risk factor has yet been found. Most
experts do not recommend that adult children of patients with Alzheimer's disease should have genetic testing for
the apoE4 gene since there is no treatment for Alzheimer's disease. When medical treatments that prevent or
decrease the risk of developing Alzheimer's disease become available, genetic testing may be recommended for
adult children of patients with Alzheimer's disease so that they may be treated.
Many, but not all, studies have found that women have a higher risk for Alzheimer's disease than men. It is
certainly true that women live longer than men, but age alone does not seem to explain the increased frequency
in women. The apparent increased frequency of Alzheimer's disease in women has led to considerable research
about the role of estrogen in Alzheimer's disease. Recent studies suggest that estrogen should not be prescribed
to post-menopausal women for the purpose of decreasing the risk of Alzheimer's disease. Nonetheless, the role
of estrogen in Alzheimer's disease remains an area of research focus.

Some studies have found that Alzheimer's disease occurs more often among people who suffered significant
traumatic head injuries earlier in life, particularly among those with the apoE 4 gene.

In addition, many, but not all studies, have demonstrated that persons with limited formal education - usually less
than eight years - are at increased risk for Alzheimer's disease. It is not known whether this reflects a decreased
"cognitive reserve" or other factors associated with a lower educational level.

How is the diagnosis of Alzheimer's disease made?

As of June 2007, there is no specific "blood test" or imaging test that is used for the diagnosis of Alzheimer's
disease. Alzheimer's disease is diagnosed when: 1) a person has sufficient cognitive decline to meet criteria for
dementia; 2) the clinical course is consistent with that of Alzheimer's disease; 3) no other brain diseases or other
processes are better explanations for the dementia.

What other conditions should be screened for?

There are many conditions that can cause dementia, to include the following:

Neurological disorders: Parkinson's disease, cerebrovascular disease and strokes, brain tumors, blood clots,
and multiple sclerosis can sometimes be associated with dementia although many patients with these conditions
are cognitively normal.

Infectious diseases: Some brain infections such as chronic syphilis, chronic HIV, or chronic fungal meningitis
can cause dementia.

Side effects of medications: Many medicines can cause cognitive impairment, especially in elderly patients.
Perhaps the most frequent offenders are drugs used to control bladder urgency and incontinence. "Psychiatric
medications" such as anti-depressants and anti-anxiety medications and "neurological medications" such as anti-
seizure medications can also be associated with cognitive impairment.

If a physician evaluates a person with cognitive impairment who is on one of these medications, the medication is
often gently tapered and/or discontinued to determine whether it might be the cause of the cognitive impairment. If
it is clear that the cognitive impairment preceded the use of these medications, such tapering may not be
necessary. On the other hand, "psychiatric," "neurological," and "incontinence" medications are often
appropriately prescribed to patients with Alzheimer's disease. Such patients need to be followed carefully to
determine whether these medications cause any worsening of cognition.

Psychiatric disorders: In older persons, some forms of depression can cause problems with memory and
concentration that initially may be indistinguishable from the early symptoms of Alzheimer's disease. Sometimes,
these conditions, referred to as pseudodementia, can be reversed. Studies have shown that persons with
depression and coexistent cognitive (thinking, memory) impairment are highly likely to have an underlying
dementia when followed for several years.

Substance Abuse: Abuse of legal and/or illegal drugs and alcohol abuse is often associated with cognitive
impairment.

Metabolic Disorders: Thyroid dysfunction, some steroid disorders, and nutritional deficiencies such as vitamin
B12 deficiency or thiamine deficiency are sometimes associated with cognitive impairment.

Trauma: Significant head injuries with brain contusions may cause dementia. Blood clots around the outside of
the brain (subdural hematomas) may also be associated with dementia.

Toxic Factors: Long term consequences of acute carbon monoxide poisoning can lead to an encephalopathy
with dementia. In some rare cases, heavy metal poisoning can be associated with dementia.
Tumors: Many primary and metastatic brain tumors can cause dementia. However, many patients with brain
tumors have no or little cognitive impairment associated with the tumor.

The Importance of Comprehensive Clinical Evaluation

Because many other disorders can be confused with Alzheimer's disease, a comprehensive clinical evaluation is
essential in arriving at a correct diagnosis. Such an assessment should include at least three major components;
1) a thorough general medical workup, 2) a neurological examination including testing of memory and other
functions of thinking , and 3) a psychiatric evaluation to assess mood, anxiety, and clarity of thought.

Such an evaluation takes time - usually at least an hour. In the United States healthcare system, neurologists,
psychiatrists, or geriatricians frequently become involved. Nonetheless, any physician may be able to perform a
thorough evaluation.

The American Academy of Neurology has published guidelines that include imaging of the brain in the initial
evaluation of patients with dementia. These studies are either a noncontrast CT scan or an MRI scan. Other
imaging procedures that look at the function of the brain (functional neuroimaging), such as SPECT, PET, and
fMRI, may be helpful in specific cases, but generally are not needed. However, in many healthcare systems
outside of the United States, brain imaging as not a standard part of the assessment for possible Alzheimer's
disease.

Despite many attempts, identification of a blood test to diagnose Alzheimer's disease has remained elusive. As of
June 2007, such testing is neither widely available nor recommended.

What is the prognosis for a person with Alzheimer's disease?

Alzheimer's disease is invariably progressive. Different studies have stated that Alzheimer's disease progresses
over two to 25 years with most patients in the eight to 15 year range. Nonetheless, defining when Alzheimer's
disease starts, particularly in retrospect, can be very difficult. Patients usually don't die directly from Alzheimer's
disease. They die because they have difficulty swallowing or walking and these changes make overwhelming
infections, such as pneumonia, much more likely.

Most persons with Alzheimer's disease can remain at home as long as some assistance is provided by others as
the disease progresses. Moreover, throughout much of the course of the illness, individuals maintain the capacity
for giving and receiving love, sharing warm interpersonal relationships, and participating in a variety of meaningful
activities with family and friends.

A person with Alzheimer's disease may no longer be able to do math but still may be able to read a magazine
with pleasure. Playing the piano might become too stressful in the face of increasing mistakes, but singing along
with others may still be satisfying. The chessboard may have to be put away, but playing tennis may still be
enjoyable. Thus, despite the many exasperating moments in the lives of patients with Alzheimer's disease and
their families, many opportunities remain for positive interactions. Challenge, frustration, closeness, anger,
warmth, sadness, and satisfaction may all be experienced by those who work to help the person with Alzheimer's
disease. For more, please read the Caregiving and Alzheimer's Disease: Caregiving Challenges articles.

The reaction of a patient with Alzheimer's disease to the illness and his or her capacity to cope with it also vary,
and may depend on such factors as lifelong personality patterns and the nature and severity of stress in the
immediate environment. Depression, severe uneasiness, paranoia, or delusions may accompany or result from
the disease, but these conditions can often be improved by appropriate treatments. Although there is no cure for
Alzheimer's disease, treatments are available to alleviate many of the symptoms that cause suffering.