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Risk factors

What are risk factors?

Many diseases have specific causes. For example, a virus causes measles. The causes of many chronic diseases or conditions, however, are unknown or uncertain. In their search for answers, scientists look for factors that appear to be linked to the development of a disease. These are "risk factors." If they are present, there is an increased chance, but not a certainty, that the disease will develop. Risk factors are characteristics of the person, lifestyle, environment, and genetic background that contribute to the likelihood of getting a disease. Some risk factors can be changed (e.g., lowering blood pressure); other risk factors cannot be changed (e.g., genetic makeup).

Risk factors on their own are not causes of a disease.

They suggest an increased chance but not a certainty that the disease will develop. Similarly, having little or no exposure to known risk factors does not necessarily protect a person from developing Alzheimer's disease.

Scientists believe that Alzheimer's disease is caused when there are too many risk factors, and they overwhelm the brain’s natural self-repair mechanisms. This reduces the brain's ability to maintain healthy nerve cells.

Further research will help deepen our understanding of the role of risk factors in developing Alzheimer's disease.

It is important to identify the risk factors for Alzheimer's disease so that people can make lifestyle choices that help reduce the chance of developing the disease. See section below on Reducing the risk.

How are risk factors determined?

Two types of studies are used to determine risk factors. One approach is to study people who have the disease and compare them with people who are similar in age, gender and other characteristics, but do not have the disease. This is known as a case-control study. Information is gathered on their personal and family characteristics, as well as on past exposures that may have occurred through lifestyle and work. Risk factors occur more often in those with the disease than in those without it. Risk factors are still seen in the group who do not have Alzheimer's disease, but not as often. This method was used in the first analysis of risk factors for Alzheimer's disease from the Canadian Study of Health and Aging (CSHA).1

The second approach is to monitor a group of healthy people over a long period of time. This is known as a cohort study. From this group, people with particular characteristics (such as a tendency towards high blood pressure) or similar lifestyles (such as vegetarianism) are compared to people without those characteristics or lifestyles to see if there is a difference in how often the two groups develop a disease. Factors that are known to be associated with a specific disease, such as obesity in the case of Alzheimer's disease, are of particular interest in cohort studies. Using these approaches, characteristics and exposures that occur more often with the disease can be identified. This approach was used in the second analysis of risk factors for Alzheimer's disease from the Canadian Study of Health and Aging.2

What are the risk factors for Alzheimer's disease?

Age

Age is the most important risk factor. As we age, our body's ability to repair itself becomes less efficient. The extent by which the self-repair of our brains diminishes varies from person to person, and these differences contribute to an individual's susceptibility to Alzheimer's disease as he or she ages. As well, many of the other known risk factors for the disease tend to increase with age (such as high cholesterol and being overweight). However, risk factors do not cause Alzheimer's disease on their own. The brain has to reach a certain critical age for the disease to occur. The older you become the higher the risk: one in 20 Canadians over age 65, and one in four of those over age 85 are affected by Alzheimer's disease. 

Family history and genetics

  • Familial Alzheimer's disease (FAD)

A very small percentage of people with Alzheimer's disease (less than 5%) have Familial Alzheimer's disease or FAD (formerly known as "early onset Alzheimer's disease"). At some point in their family history certain genes mutated and developed the abnormal characteristics that cause FAD. These inherited genes have a powerful influence: if one parent has FAD, each child has a 50 % chance of inheriting the disease. These inherited genes differentiate FAD from the more common sporadic form of Alzheimer's disease, but the disease itself is identical.

  • Sporadic Alzheimer's disease

The sporadic form of Alzheimer's disease, which used to be called "late onset Alzheimer's disease," was formerly assumed to have no family linkages. However, it's now known that a person with a direct relative (parent or sibling) with Alzheimer's disease has a three times greater chance of developing the disease than someone who does not.* The risk increases further if both parents have the disease. So aside from the FAD-related genes there are Alzheimer's disease–related genetic factors shared by family members.

New research is revealing more and more genetic risk factors for the sporadic form of Alzheimer's disease. That means that these genes are found to a greater extent among those with the disease, though they are also found in people without Alzheimer's disease. People with these genetic risk factors are not in the same high-risk category as people who have the genes responsible for FAD. In fact, the risk associated with any one of these genetic risk factors is lower than the risk associated with having a parent with the sporadic form of the disease (other than the apoE4 gene discussed below).

*Here is a useful way of looking at the relative risk: of 100 people with no defined genetic risk factor, five will get Alzheimer's disease at age 65 or older (and 95 will not). Of 100 people, each with a parent with Alzheimer's disease, 15 will get Alzheimer's disease at age 65 or older (and 85 will not).

  • ApoE4 gene

This gene is the most important genetic risk factor for the sporadic form of Alzheimer's disease. ApoE genes regulate the production of a protein that helps carry cholesterol and other fats in the blood to the cells of the body. Of the three variants of the apoE gene (apoE2, apoE3 and apoE4), the apoE4 variant is associated with an increased risk of Alzheimer's disease.

In our cells (except ova and sperm) all genes are paired, one being contributed by the father and one by the mother. If a person's pair of apoE genes includes one apoE4 gene, her risk of developing Alzheimer's disease is increased. However, approximately half of all people with two apoE4 genes will develop Alzheimer's disease at age 65 or older. People with no apoE4 genes can still get the disease and people with two apoE4 genes will not necessarily get the disease.

Female gender

Twice as many women get Alzheimer's disease than men. Many believe that it is in a large part a result of the changes to women's hormones at menopause, in particular the decline of the important hormone estrogen. In the past, estrogen was often prescribed to relieve symptoms of menopause and to reduce the risk of developing Alzheimer's disease. However, a large-scale clinical study recommended stopping hormone replacement therapy (HRT) because of potentially dangerous side effects. Many researchers believe HRT is worthy studying, especially in the context of Alzheimer's disease. Any decision regarding the use of HRT should first be discussed with your doctor.

Hormonal changes are not the only factor contributing to the increased incidence of Alzheimer's disease in women. On average, women live longer than men and age is a risk factor. Women are also more prone to diabetes, which is also a risk factor (see below), and recently, a gene was identified that occurs only in women, and appears to somewhat increase the risk for Alzheimer's disease.

Removal of the ovaries

There may also be a connection between removal of the ovaries and the risk of Alzheimer’s disease. The removal of the ovaries triggers menopause, and removes the source of most of the body’s estrogen. Estrogen may protect the brain from age-related changes that could lead to cognitive impairment and dementia. This finding is inconclusive and further research is needed.

Cardiovascular disease

All the risk factors for cardiovascular disease (such as high blood pressure and high cholesterol levels) are risk factors for both Alzheimer's disease and vascular dementia. Strokes and mini-strokes are well-accepted risk factors for Alzheimer's disease and for vascular dementia.

Diabetes

Type 2 ("Adult") diabetes is a known risk factor for Alzheimer's disease. The two diseases are linked by cardiovascular disorders, which are associated with diabetes and are risk factors for Alzheimer's disease. We also know that the use of glucose in the brains of people with Alzheimer's disease is impaired, similar to the situation in the bodies of people with type 2 diabetes.

Recently, researchers have found that the Alzheimer's brain may have a diabetes-like condition that some are calling type 3 diabetes. In people with Alzheimer's disease, the production of insulin in the brain is reduced and the nerve cells are less sensitive to it. (Production of insulin in the brain is separate from insulin production in the pancreas, the major insulin-producing organ). Anti-diabetic drugs that target the brain are now being tested in people with Alzheimer's disease.

Recently, evidence was also presented that children with type 1 ("Juvenile") diabetes are at risk for developing Alzheimer's disease in later life.

Down syndrome

Almost all individuals with Down syndrome who live into their forties or older develop the plaques and tangles that characterize Alzheimer's disease. However, not all people with Down syndrome who develop these brain changes go on to develop dementia. Probably, these people may not yet have developed other age-induced changes that occur in most people with Alzheimer's disease. 

Mild cognitive impairment

In mild cognitive impairment (MCI), there is a level of cognitive and/or memory impairment beyond that expected for normal aging but not advanced enough to be called "dementia" or "Alzheimer's disease." Up to 85 per cent of people with MCI, who are often in their early forties or fifties, will develop Alzheimer's disease within ten years. Therefore, MCI is an important risk factor for the disease. Researchers now know that the abnormal changes in the brain characteristic of Alzheimer's disease can begin to appear in people diagnosed with MCI twenty or more years before there are signs of dementia. Brain imaging may make it possible to detect the most at-risk individuals with MCI, and research to this end is ongoing.

Head injury

Most clinicians accepted brain injuries at any age, especially repeated concussions, as risk factors for the later development of Alzheimer's disease.

Low levels of formal education

Several studies have shown that people with less than six years of formal education may have a higher risk of developing Alzheimer's disease. It was thought that the brain stimulation from learning provides a protective effect for the brain. New studies show that it may be that factors often associated with low educational background, such as unhealthy lifestyle, account for the risk, rather than low educational level itself.

Other risk factors

Other risk factors for Alzheimer's disease include: inflammatory conditions (reflecting a possible immune system malfunction), a history of clinical depression, stress, and inadequate exercising of the brain. Risk factors that are less firmly established include smoking, excessive alcohol consumption and drug abuse.

Aluminum

Most researchers no longer regard aluminum as a risk factor for Alzheimer's disease. Some researchers are still examining whether some people are at risk because their bodies have difficulty handling foods containing the metals copper, iron, and aluminum.

Reducing the risk

Although genes play an important role in the development of Alzheimer’s disease, a healthy lifestyle may help us reduce the risk. It has been estimated that up to half the cases of Alzheimer’s disease worldwide may be the result of seven key modifiable risk factors: diabetes, high blood pressure, obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity.3

A healthy lifestyle includes healthy eating, maintaining a healthy weight, taking part in regular physical activity (which can be quite modest), maintaining normal blood pressure and cholesterol levels and participating in activities that involve socializing and stimulating brain activity. For more information on reducing your risk, see the Brain health section.

Need further information?

For more information on risk factors, download the following PDF file:

A Report on Alzheimer Disease and Current Research by Dr. Jack Diamond, former Scientific Director Emeritus, Alzheimer Society of Canada, 2011 (44 pages)

Alzheimer Society Information Sheets are available from your local Alzheimer Society.

Footnotes:

  1. (1994). Canadian Study of Health and Aging: Risk factors for Alzheimer's Disease in Canada. Neurology, 44:2073–2080.
  2. (2002). Risk Factors for Alzheimer's Disease: A Prospective Analysis from the Canadian Study of Health and Aging, American Journal of Epidemiology, 156(5), 445–453.
  3. (2011) The projected effect of risk factor reduction on Alzheimer's disease prevalence, The Lancet Neurology, http://www.thelancet.com/journals/lancet/article/PIIS1474-4422(11)70072-2/abstract
[The contents of this document are provided for information purposes only, and do not represent advice, an endorsement or a recommendation, with respect to any product, service or enterprise, and/or the claims and properties thereof, by the Alzheimer Society of Canada.]

Last Updated: 04/09/14