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Non-Genetic Risk Factors
 Age
Education level
Head trauma
Early life experiences
Dietary factors
High blood pressure and high cholesterol
Metals, such as aluminum and zinc
Genetic (Inherited) Factors
Age
During the course of normal aging, the brain undergoes a number of changes:
- Some neurons (nerve cells) in certain brain regions die, although most neurons important
to learning are spared;
- Some neurons and the fibers that connect them to other neurons shrink and
degenerate, especially neurons
 in areas of the brain important to learning,
memory, planning and other complex mental activities;
- Tangles develop within neurons and protein plaques develop in the areas
surrounding neurons;
- Tiny structures inside neurons that metabolize energy for cell functions
(mitochondria) become more susceptible to damage;
- Inflammation (swelling) increases, which can injure nerve cells;
- Oxidative stress, which is caused by the release of molecules called
free radicals from normal cellular processes, increases, leading to
nerve cell damage and death.
In healthy older people, the impact of these changes may be modest, resulting in various degrees of age-related memory decline. In people who have Alzheimer's, however, some of these changes are much more extreme, with devastating consequences. Determining how the brain changes in normal aging and what relevance this has to Alzheimer's is an important area of research.
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Education level
Research suggests that the more years of formal education one has,
the less likely one is to develop Alzheimer's. Some experts theorize
that longer education may produce a denser network of synapses,
the nerve-fiber connections that enable neurons to communicate with
one another. This may create a kind of "neural reserve"
that enables people to compensate longer for the early brain changes
associated with Alzheimer's.
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Head trauma
Some studies have found that Alzheimer's occurs more often in people
who have suffered traumatic brain injury earlier in life. Ongoing research
is pursuing this link further. A history of head injury is clearly a risk factor for Alzheimer's in
people who carry the APOE e4 Alzheimer's gene.
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Early life experiences
The environment in which one lives early in life has been implicated
as a risk factor for many adult chronic diseases, including Alzheimer's.
Results of a recent study indicated that an increased number of
siblings was associated with increased risk of Alzheimer's and that
growing up in the suburbs was associated with a decreased risk.
These associations were not explained by patients' educational level
or whether they carried the APOE gene that is associated with Alzheimer's.
Such results appear to support a possible link between socioeconomic
or environmental variables and altered brain growth and development,
which in turn may affect the risk of developing Alzheimer's disease later in life.
A number of investigators have conducted these types of epidemiological
studies to learn more about whether and to what extent early life events and
other factors have an impact on the development of Alzheimer's. Several intriguing
possibilities have emerged from these studies. For example, results from one
recent study indicated that rural residence in childhood, combined r with fewer
than six years of school, was associated with increased risk for Alzheimer's.
Though such findings can be suggestive and interesting, they can also be conflicting
or incomplete, partly because investigators looking at the same issues may use
different study methods and partly because of the complexity of the issues and
the large number of variables involved. For example, low educational attainment
may actually be a surrogate or marker for other deleterious socioeconomic or
environmental influences in childhood. Nevertheless, epidemiological
research is a valuable complement to basic research on AD, and ongoing and future
studies show promise for shedding further light on the relationship among AD
risk, early life events and other factors.
Estrogen loss after menopause: Please see the section on "Research
on Preventing Alzheimer's Disease" for more information
on the link between estrogen and Alzheimer's risk.
Use of non-steroidal anti-inflammatory drugs: Please see the section
on "Research on
Preventing Alzheimer's Disease" for more information on
the link between these popular pain relievers and Alzheimer's risk.
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Dietary factors
The evidence that what you eat matters to your brain is growing
fast. A slew of large studies recently reported have linked dietary
habits and specific nutritional factors to the risk for Alzheimer's
disease or cognitive decline. In particular, the benefits to the
brain of a low-fat diet rich in antioxidants such as vitamins E
and C throughout life are becoming clearer.
Here's what some of the latest studies have found:
- A diet rich in foods containing vitamin E may help protect against
Alzheimer's in some people, according to a study conducted at Rush-Presbyterian-St.
Luke's Medical Center in Chicago and reported in the prestigious Journal
of the American Medical Association (JAMA). Such foods include vegetable oils, nuts, green leafy vegetables, and whole grains. A protective
effect was NOT seen when study participants took vitamin E supplements, as
opposed to getting more of the vitamin from foods. The most significant protective
effect was found among those who had the highest dietary intake of vitamin
E (which averaged 11.5 International Units per day); their risk of developing
Alzheimer's was 67 percent lower than people who consumed the least amount
of vitamin E from food sources. The researchers also found that vitamin E
is associated with protection against more general cognitive decline. Ongoing
clinical trials are investigating whether vitamin E might be useful as a treatment
for Alzheimer's, and if it can help prevent the disease.
- A large study reported at the 2002 International Conference on Alzheimer's
Disease found that a low-fat, antioxidant-rich diet was associated
with decreased risk of Alzheimer's disease, an association that held up even
in people who carry the APOE-4 gene, the only known genetic risk factor for
late-onset Alzheimer's. Researchers at Case Western Reserve University School
of Medicine found that people who ate primarily lean meats (fish and poultry)
and fruits and vegetables during midlife had a lower risk of developing Alzheimer's
than people who ate a diet higher in fat and sugar and consisting of larger
amounts of red and processed meats.
- A Netherlands study published in JAMA reported a link between
high dietary intake of vitamins E and C and protection against Alzheimer's
disease in certain people. Both vitamins have antioxidant properties
that experts believe may help reduce damage to nerve cells caused by oxidative
stress, which occurs throughout the body as a natural consequence of aging
and may contribute to Alzheimer's disease in ways that are not fully understood.
- Two studies point to the importance of B vitamins and levels of homocysteine,
a compound found in the blood that has been linked to increased risk of certain
cardiovascular conditions, including stroke and damage to the arteries. The
first study, published in the American Journal of Clinical Nutrition,
found that increased levels of homocysteine correlated both with deficiencies
in vitamin B-12 and folic acid, another B vitamin, and with lower scores on
cognitive tests. A second study reported at a major Alzheimer's conference
found elevated homocysteine and low levels of vitamin B-12 in African-Americans
with Alzheimer's disease.
Taken as a whole, these and other studies support the notion that eating right
throughout your life is just as important to long-term cognitive health as it
is to heart health.
A number of long-term, prospective clinical trials are now underway to test
the effectiveness of vitamin E and other antioxidants in preventing or postponing
cognitive decline and Alzheimer's disease. Several are funded by the National
Institute on Aging.
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High blood pressure and high cholesterol
There is growing evidence that many of the well-established risk
factors for cardiovascular disease, including high cholesterol and
high blood pressure, may also be risk factors for Alzheimer's disease.
A large study by researchers in Finland supports this thinking.
Among the study population of 1,449 people, elevated cholesterol
and high blood pressure seemed to be more strongly linked to eventual
development of Alzheimer's than did carrying APOE-4 gene, the only known
inherited risk-factor for the most common form of the disease. Those people
who carried the APOE-4 gene were twice as likely to develop Alzheimer's
than those with no genetic risk, but if those APOE-4 carriers also
had high blood pressure, they were five times as likely to develop
the disease. When high cholesterol was also present, the risk jumped
to eight times greater than those without APOE-4. This and a number
of other studies are showing that what's good for the heart - keeping
cholesterol and blood pressure in check - may also be good for the
brain.
For more information regarding the link between cholesterol levels and Alzheimer's
disease, please see "Cholesterol-lowering
drugs" in the section titled "Research Aimed at Preventing
Alzheimer's Disease."
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Metals, such as aluminum and zinc
One of the most publicized and
controversial hypotheses about risk factors for Alzheimer's concerns
aluminum, which became a suspect when researchers found traces of
this metal in the brains of Alzheimer's patients. Many studies since
then have either not been able to confirm this finding or have had
questionable results. Aluminum does turn up in higher amounts than
normal in some autopsy studies of Alzheimer's patients, but not
in all, and the aluminum found in some studies may have come from
substances used in the laboratory to study brain tissue. Moreover,
various studies have found that groups of people exposed to high
levels of aluminum do not have an increased risk. On the whole,
scientists can say only that it is still uncertain whether exposure
to aluminum plays a role in Alzheimer's disease.
Zinc:
Zinc has been implicated in Alzheimer's disease in two ways. Some
reports suggest that too little zinc is a problem, others that too much zinc
is at fault. Too little zinc was suggested by autopsies that found low levels
of zinc in the brains of Alzheimer's disease patients, especially in the hippocampus, the part of the brain involved in learning and memory.
On the other hand, another study suggests that too much zinc might be the
problem. In this laboratory experiment, zinc caused soluble beta amyloid from
cerebrospinal fluid to form clumps similar to the plaques of Alzheimer's disease.
Current experiments with zinc are pursuing this lead in laboratory tests that
more closely mimic conditions in the brain.
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