Alzheimer's Disease and Risk Factors

What are risk factors?

Many diseases have specific causes; for example, a virus causes measles. However, for many chronic disorders (long-lasting conditions such as Alzheimer's disease), the causes remain 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 or exposures that appear to have some relationship to the development of a disease. They can include family background, work history or exposures to a substance or product. Some risk factors can be modified (for example, lowering blood pressure reduces the risk of stroke); other risk factors cannot be modified (for example, age or family history).

It is important to note that risk factors are not necessarily causes of a disease. No single study can verify a link between a disease and a specific factor; repeated studies are necessary before a causal link can be established.

How are risk factors determined?

Two types of studies are used to determine risk factors. One approach is to study people who already have the disease (such as Alzheimer's disease) and compare them with persons without the disease, who are otherwise similar in age, gender and other characteristics. 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 that are more frequent in the diseased than the non-diseased group can be identified. 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 who have a particular characteristic or who were exposed to a particular substance are compared to those without the characteristic or exposure to detect any difference in the rate at which the two groups develop a disease. Lifestyle factors (such as diet) as well as family and work histories are examined in the diseased and non-diseased groups. Factors known to be associated with a specific disease are of particular interest. In this way, characteristics and exposures that are associated with the occurrence of the disease can be identified. This approach was used in the second analysis of risk factors for Alzheimer's disease from the CSHA (CSHA-2)².

Recent data from CSHA-2 have been published identifying new areas of reduced risk for AD. These preliminary findings are important because they indicate lifestyle choices that can be made that would help protect against AD.

What are the risk factors associated with Alzheimer's disease?

AGE
The CSHA provides evidence to support age as a risk factor. The following chart shows the older you become, the higher the risk for Alzheimer's disease.

FAMILY HISTORY
Many studies indicate that people with a relative (parent, brother or sister) with Alzheimer's disease have a greater chance of developing the disease than those with no family history.

The more common form of Alzheimer's disease is called Sporadic Alzheimer's disease and accounts for 90 to 95 per cent of all cases. The role of heredity in Sporadic Alzheimer's disease is unclear and continues to be the subject of intense research.

A rare form of the disease, Familial Autosomal Dominant Alzheimer's disease (FAD), accounts for approximately 5 to 10 per cent of all cases and is known to be inherited—the disease will occur if the disease gene is present. (Each chromosome carries many genes that are strung together like beads on a string. These genes are the basic units that allow specific characteristics to be passed from one generation to the next.)

In certain families, FAD is passed directly from one generation to another through a dominant inheritance pattern. This means that if a parent is affected, each child has a 50 per cent chance of inheriting the disease gene and will develop Alzheimer's disease in adulthood.

Please refer to the Alzheimer Society’s Information Sheet on Alzheimer's Disease and Heredity for more information.

APOE GENE
Chromosome 19 has the apolipoprotein E gene (APOE) that affects cell activity. The APOE gene has three alleles*: APOE e2, APOE e3 and APOE e4. The presence of the e4 allele is associated with an increased risk of Alzheimer's disease with an earlier age of onset (i.e., before age 70). The APOE gene cannot predict Alzheimer's disease, but it may be useful in confirming diagnosis. It should be noted that the absence of the e4 allele reduces the risk of Alzheimer's disease.

*Alleles are copies of a gene. A person inherits two alleles of a gene, one from the mother and one from the father. Please refer to the Alzheimer Society’s Information Sheet on Alzheimer's Disease and Heredity for more information.

DOWN SYNDROME
Almost all individuals with Down syndrome over the age of 40 have changes to brain cells typical of Alzheimer's disease. In these individuals, dementia usually develops in their 50’s or 60’s.4

Please refer to the Alzheimer Society’s Information Sheet on Alzheimer's disease and Down Syndrome for more information.

COGNITIVE IMPAIRMENT WITH NO DEMENTIA (CIND) or MILD COGNITIVE IMPAIRMENT (MCI)
In the CSHA, a group of participants was identified as having mild cognitive impairment, but did not meet the clinical definition of having dementia. This group was followed for several years, and recent evidence has indicated that of the survivors, 5 to 6 per cent of the group developed Alzheimer's disease annually. Research into the progression of CIND or MCI is ongoing.

HEAD INJURY
Some studies have shown that people who have had a head injury with loss of consciousness have an increased chance of developing Alzheimer's disease. To prevent head injury and therefore possibly prevent dementia, it would be prudent to use helmets for sports activities, such as cycling, and safety belts when driving in a vehicle.

EDUCATION
Several studies have shown that people who have less than six years of formal education appear to have a higher risk of developing Alzheimer's disease. Low education may reflect early experiences that were not beneficial to brain development. Or, higher education may delay the onset of symptoms of Alzheimer's disease possibly due to greater brain reserve or educational activities that may stimulate brain activity. Education as a protective factor requires more study to determine whether it is education that makes a difference or other factors related to it (e.g., income level).

ANTI-INFLAMMATORY MEDICATIONS
Researches have noticed signs of inflammation in the regions of the brain of people with Alzheimer's disease. While inflammation can be a normal immune system response to injury or disease, chronic inflammation can cause damage. Thus, inflammation in the brain may contribute to nerve damage. Other research, such as the CSHA, showed that people with arthritis have a lesser chance of developing Alzheimer's disease than those without it. People with arthritis usually take non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate symptoms. At this time, NSAIDs cannot be recommended for the treatment or prevention of Alzheimer's disease. Research is ongoing in this area.

ALUMINUM
The connection between Alzheimer's disease and aluminum is still under debate in the scientific community. Some studies have indicated that exposure to aluminum in drinking water increased the chances of individuals developing Alzheimer's disease.

Please refer to the Alzheimer Society’s Information Sheet on Aluminum for more information.

ESTROGEN
Some research into hormone replacement therapy has shown that postmenopausal women who take estrogen may have a lower risk of developing Alzheimer's disease. Other research has shown that women with Alzheimer's disease who are treated with estrogen show no sign of improvement. Currently, research is inconclusive as to the role, if any, that estrogen may play in relation to Alzheimer's disease. Since hormone replacement therapy may be recommended for reasons other than Alzheimer's disease, women should be aware of the risks and benefits of estrogen use.

PHYSICAL ACTIVITY
Recent data from the CSHA-2 indicate that regular physical activity was associated with reduced risk of Alzheimer's disease. This information supports previous clinical trials showing exercise to benefit cognitive function. Identifying the protective effect of regular physical activity is an important finding as it may represent a relatively safe and available strategy to help prevent Alzheimer's disease, as well as many other chronic conditions. The CSHA-2 recommends that further research should be conducted in this area.

What other factors are being investigated?

Other factors being investigated by researchers in relation to Alzheimer's disease include:

•  existing diseases or conditions that a person may have (such as heart disease, high cholesterol or high homocysteine levels in the blood)
•  toxins in the environment (such as fertilizers or pesticides)
•  antioxidants (such as vitamin E)
•  lifestyle choices (such as wine and coffee consumption, and diet)

What is our current understanding of risk factors?

In general, scientists today believe that Alzheimer's disease is caused by several factors, including those that are inherited and those that are not.

Additional risk factors may be identified as more studies are carried out. Uncovering risk factors increases our understanding of the disease and is a step towards solving the Alzheimer puzzle.

¹ Canadian Study of Health and Aging: Risk factors for Alzheimer’s Disease in Canada. Neurology 1994; 44:2073-2080.
² Risk Factors for Alzheimer’s Disease: A Prospective Analysis from the Canadian Study of Health and Aging, American Journal of Epidemiology 2002; Vol. 156, No. 5, 445-453.
³ Canadian Study of Health and Aging Working Group. Canadian Study of Health and Aging: study methods and prevalence of dementia. Canadian Medical Association Journal 1994; 150:899-913, and personal communication, CSHA.
⁴ Preventing Dementia, S.E. Black, C. Patterson, J. Feightner, The Canadian Journal of Neurological Sciences 2001; 28: Suppl. 1—S56-S66.
⁵ Management of Dementing Disorders: Conclusions from the Canadian Consensus Conference on Dementia, Supplement to CMAJ 1999; 160 (12 Suppl), S5.

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.

Source: Alzheimer's Disease and Risk Factors - Alzheimer Society of Canada.