Well-Established Risk Factors

Alzheimers Risk Factors

Keep in mind that risk factors are traits or behaviors that may make you statistically more likely than others in the general population to have a certain condition. They are not necessarily "causes" of the condition.



Clear risk factors for Alzheimer's disease include:

• Increasing Age


• Family history, genetics, Down syndrome


• Being female


• Environmental factors

Increasing age

This is the main risk factor. The older you grow, the greater your risk.

• From age 65 to 74, about 3% of people have Alzheimer's
  
  
  
  


• From age 75 to 84, the figure rises to 19%
  
  
  
  


• And for those 85 and older, Alzheimer's afflicts 47%

Currently the U.S. population is aging, with people over 85 becoming the nation's fastest-growing age group. Because this is also the group most affected by Alzheimer's disease, experts warn that unless researchers discover how to prevent the disease, by the year 2050, as many as 15% of those over 65 might have Alzheimer's.



However, according to the Multi-Institutional Research in Alzheimer's Genetic Epidemiology (MIRAGE) project based at the Boston University School of Medicine, Alzheimer's risk declines after age 90.

Family history, genetics, Down syndrome

If one identical twin develops Alzheimer's disease, the other's risk is unusually high -- 40% to 50%, which argues for a genetic predisposition to the disease.



In addition, having any close relative who develops Alzheimer's increases risk. In a 1996 study, researchers with the MIRAGE project tracked the lifetime Alzheimer's risk of about 13,000 people who had a first-degree relative (mother, father, sister, brother, son, daughter) with the condition. By age 80, people with Alzheimer's disease in both parents had a 54% risk, 1.5 times the risk of Alzheimer's in people with just one affected parent, and 5 times the risk of people with two unaffected parents.



The genetic mechanisms of Alzheimer's among families remain largely unexplained, but researchers have identified a few genetic mutations that greatly increase risk in some families. Research has focused on specific abnormalities of genes on chromosomes 1, 14, and 21.



The mutation involving chromosome 21 causes Down syndrome. Instead of having a pair of this chromosome, people with Down syndrome are born with three. Down syndrome causes a characteristic physical appearance, and a particular form of mental retardation. Until fairly recently, people with this condition usually died in their 30s, but today many live longer. If people with Down syndrome live into their 40s or 50s, they almost always develop Alzheimer's disease. On autopsy, the brains of Down and Alzheimer's sufferers are often indistinguishable.



Chromosome 21 contains the gene for amyloid precursor protein (APP), which appears to play a role in depositing beta-amyloid, the substance involved in the senile plaques of Alzheimer's disease. People with Down syndrome appear to produce extra APP, which in turn leads to unusually high levels of beta-amyloid peptide. This may explain why people with Down syndrome develop Alzheimer's disease at unusually young ages.



The mutations on chromosomes 1 and 14 cause rare clusters of Alzheimer's disease in small numbers of families. The defects on chromosome 14 happen in a gene called presenilin-1. It appears to play a major role in early-onset hereditary Alzheimer's disease, accounting for up to 80% of cases of this type of Alzheimer's.



Finally, Cherokee Indians appear to have genetic resistance to Alzheimer's disease. Scientists from the University of Texas Southwestern Medical Center in Dallas studied 52 members of the Cherokee Nation from Oklahoma. Half had Alzheimer's disease, and half did not. Using genealogical information from the Cherokee Nation Tribal Registration Department, the researchers discovered that as the proportion of Cherokee ancestry increases, Alzheimer's risk decreases.

Being female

The MIRAGE Study shows that at all ages, women have a higher risk of Alzheimer's disease than men. By age 93 women's risk is 13% higher than men's. However, women's use of postmenopausal estrogen helps prevent and treat the disease.

Environmental factors

The Finnish identical-twin study shows that genetics play a key role in Alzheimer's disease. But it also shows that genetic makeup is not destiny. Identical twins are genetically the same, but Alzheimer's disease develops in only about half of identical twin pairs. In addition, when both identical twins develop Alzheimer's, their age at diagnosis often differs by as much as 15 years. These findings suggest that environmental factors influence any genetic predisposition.



Additional support for environmental factors comes from a 1996 study of elderly Japanese men living in Hawaii. Researchers from the National Institute on Aging used information from the Honolulu Heart Program, a 30-year survey of some 4,000 Japanese-American men begun in 1965. Thirty years later, 3,734 of the men were still alive. The survivors had a rate of dementia from all causes of 9.3%, and 5.4% had Alzheimer's. This is about comparable to the dementia/Alzheimer's risk seen in white American and European populations. The researchers then compared Alzheimer's incidence in a similar group of elderly Japanese men living in Hisayama, Japan. Only 3.2% showed dementia, with 1.5% diagnosed with Alzheimer's.



The researchers did all they could to make sure that the same diagnostic criteria for Alzheimer's were used in the Japanese-American and native Japanese men. They concluded that "environmental or cultural factors associated with migration from Japan to Hawaii may have influenced the development of Alzheimer's disease."

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