7 Risk Factors for Alzheimer's Disease

Despite tremendous advances in the understanding of Alzheimer’s disease, scientists have yet to pinpoint the causes of the disorder. Risk factors for Alzheimer’s include older age, being female, having an affected family member, cardiovascular disorders (such as high blood pressure, high cholesterol and heart attack), Down syndrome, and head injury. Here’s what to know about each one.

1. Older age

Older age is the strongest risk factor for Alzheimer’s disease. The likelihood of developing the disease doubles every five years beginning at age 65. After age 95, the risk reaches nearly 50 percent. Some evidence suggests that the number of new cases begins to drop off after age 90, though other research shows that it may increase. This is an important issue to resolve, since a risk that continues to rise without leveling off would suggest that it is an inherent aspect of aging.

2. Being a woman

Most researchers now agree that women are at higher risk for developing Alzheimer’s disease than men, even when women’s longer lifespans are taken into account. It is not clear exactly why women are more vulnerable to the disease. Researchers are studying whether decreased levels of estrogen after menopause are responsible or whether rising rates of vascular disease (possibly attributable to decreased estrogen) contribute.

3. Genetics

Having a family member who has Alzheimer’s increases the risk of developing the disease. However, only a handful of Alzheimer’s patients—fewer than 2 to 3 percent—have the disease as a result of a one of three identifiable defective genes (a gene mutation). In families with one of those mutations, Alzheimer’s disease is carried as a dominant trait (which means that each offspring has a 50 percent chance of inheriting the abnormal gene) on one of the three chromosomes—the amyloid precursor protein (APP) gene on chromosome 21, the presenilin-1 (PS-1) gene on chromosome 14 and the presenilin-2 (PS-2) gene on chromosome 1.

The prevalence of these gene mutations is low. As an example, the defective APP gene has been found in only 25 families worldwide. Although these mutations affect only a small number of families, a person carrying one of them will inevitably develop Alzheimer’s if he or she lives long enough. Those with an altered APP gene usually develop the disease between ages 40 and 65. Those who carry a PS-1 mutation may show signs of Alzheimer’s as early as age 30, whereas people with PS-2 defects develop the disease between ages 40 and 90.

Researchers have already found more than 20 other genetic abnormalities linked to Alzheimer’s disease. For example, scientists have pinpointed an area on chromosome 10 that appears to contain genes that influence the risk of developing or avoiding the disease. Each of those genes is likely to contribute only a little bit to the overall incidence of the disease, probably less than 1 percent.

Having a genetic predisposition to Alzheimer’s disease is different from carrying a genetic mutation. A predisposition means that, although the disease “runs in the family,” it is not associated with one of the genetic defects discussed above. Some family members develop the disease while others do not.

A predisposition suggests that other risk factors interact with a person’s genetic makeup to increase the chance that he or she will develop Alzheimer’s or to cause the disease to begin earlier in life. In one study of identical twins, who share an identical genetic makeup, the age of Alzheimer’s onset varied by as much as 15 years.

By studying people from different ethnic, racial and social groups, scientists may discover the full range of additional risk factors. These findings, in turn, could provide new insights into what triggers Alzheimer’s disease.

4. Cardiovascular disease

Numerous risk factors for cardiovascular disease also appear to be risk factors for Alzheimer’s disease. These include elevated LDL cholesterol levels, low HDL cholesterol levels, high blood pressure, smoking, overconsumption of unhealthy fats, excess body weight, lack of exercise and type 2 diabetes (now considered to be a cardiovascular risk factor equivalent).

5. Down syndrome

The risk of Alzheimer’s disease is three to five times higher among people with Down syndrome than in the general population. The genetic abnormality responsible for Down syndrome is located on chromosome 21, the chromosome containing the amyloid precursor gene.

6. Head injury

There appears to be a strong link between serious head injury and risk of developing Alzheimer’s disease later in life. A moderate head injury (defined as a loss of consciousness for more than 30 minutes) is associated with a two times greater risk of developing the disease, and a severe head injury (defined as a loss of consciousness for more than 24 hours) is associated with a 4.5 times greater risk.

Because of this, doctors recommend always wearing a seat belt in moving vehicles and a helmet while bicycling to protect the brain from injury.

7. Depression

Several studies have suggested that experiencing depression may increase a person’s susceptibility to Alzheimer’s disease later in life.

Two studies reported in the Archives of General Psychiatry found an association between depression and the development of Alzheimer’s disease. In one, researchers analyzed the results of several well-conducted studies and found that a history of depression doubled a person’s risk of developing Alzheimer’s disease.

The other study explored the possible link between depression and the formation of beta-amyloid plaques and neurofibrillary tangles (the hallmark brain abnormalities found in Alzheimer’s disease).

The researchers examined the brains of 102 people who had died of Alzheimer’s disease—50 had a lifetime history of depression and 52 had no history of depression. They found that brains from people who had suffered from depression had more plaques and tangles in the hippocampus than did the brains from people without a history of depression.

Moreover, when the researchers reviewed the medical records of the Alzheimer’s patients, they discovered that cognitive decline was more rapid in those with a history of depression. It is not clear whether treating depression can reduce the risk of developing Alzheimer’s.

Other possible risk factors

Other conditions that have been considered possible triggers of Alzheimer’s disease include immune system malfunctions, endocrine (hormonal) disorders, slow-acting viruses or bacteria, vitamin deficiencies, exposure to electromagnetic fields and accumulation of metals such as zinc, copper, iron and aluminum in the body. However, no solid evidence supports an association with any of these factors.

The discovery of larger-than-expected amounts of aluminum in the brains of some people who died of Alzheimer’s generated a great deal of publicity a number of years ago. Worried that aluminum might somehow promote the disease, many people threw away cans, cookware, cosmetics, antacids, antiperspirants and other items containing the metal.

However, studies of people exposed to large quantities of aluminum did not reveal an increased risk of dementia. Most likely, aluminum deposits in brain tissue are a result—not a cause—of the underlying abnormalities associated with Alzheimer’s disease. (Incidentally, more aluminum leaches into soft drinks from glass bottles—which contain approximately 1 percent aluminum—than from aluminum cans, which are coated with a thin layer of plastic.)