Alzheimer's Research on Causes and Risk Factors - Non Genetic Risk Factors

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Topics:
- Age
- Education level
- Head trauma
- Early life experiences
- Dietary factors
- High blood pressure and high cholesterol
- Metals, such as aluminum and zinc

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.

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.

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.

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.

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.

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."

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.