Biology is not always destiny in Alzheimer's, says new twins data

July 21, 2004

PHILADELPHIA, July 21, 2004 - When one twin develops Alzheimer's disease, the other does not always develop the disorder, a study of male twins who served in World War II shows. The study finds that identical twins, who share nearly identical genes, both develop Alzheimer's by their late 70s only about 40 percent of the time. In fraternal twins, who are no more genetically similar than other siblings, both twins develop Alzheimer's by their late 70s only about 20 percent of the time.

Brenda L. Plassman, Ph.D., of Duke University Medical Center, reported these findings at The 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association.

In another study at ICAD, researchers found that disclosure to persons that they have the one known gene that raises late-onset Alzheimer risk did not increase anxiety about developing Alzheimer's disease for the vast majority of participants.

20-40 Percent Likelihood of Both Twins Affected by Alzheimer's
Plassman's twin data show that when both twins develop Alzheimer's, their average age of onset differs by about five years. Those five years dovetail with a widely cited 1998 study by biostatistician Ronald Brookmeyer and colleagues, who projected that finding a tactic to delay Alzheimer's disease onset by just five years could reduce the number of cases by half over the next 50 years.

"Data from these World War II veterans suggest that, even barring any conscious effort to change the course of Alzheimer's, there are environmental factors at work that can affect the age of onset by that critical five-year margin," Plassman notes.

As part of the ongoing study, Plassman and her colleagues will look at factors that may alter the age of onset, including head injury, medications and coexisting medical conditions such as diabetes, high blood pressure and other risk factors for heart disease and stroke. The Alzheimer's Association is funding one part of this study investigating the effect of occupational complexity on delaying or preventing dementia.

"As the twins age and greater numbers develop Alzheimer's, the study will gain more power in assessing the effects of these environmental and health factors," Plassman says.

Low Level of Education is a Risk Factor for Alzheimer's Disease
Data from the Swedish Twin Registry has been used to explore the roles of both genetic and environmental factors. In identical twins in the registry, if one twin has Alzheimer's disease, 59% of the time the other twin will also have Alzheimer's disease. For same sex fraternal twins, if one twin has Alzheimer's disease, 32% of the time the other twin will as well. Concordance for unlike sex fraternal twins was 24%.

"These results mean that environment must be helping to explain why one twin develops dementia and the other does not," said Margaret Gatz, Ph.D., of the University of Southern California.

At ICAD, Gatz and her colleagues focused on one important environmental factor - level of education. In work funded by the Alzheimer's Association and the National Institute on Aging, Gatz and her colleagues studied both identical and fraternal twins as well as unrelated individuals. Gatz found that less education is a risk factor for all groups, including identical twins who begin life with very similar genetic predisposition to intellectual achievement. However, these new results show that genes do not account for the relationship between fewer years of education and increased dementia risk.

"The reason that low education is related to higher risk of Alzheimer's disease appears to a great extent to relate to environmental influences," Gatz said.

The researchers conclude that the relationship between low education and increased dementia risk may represent the effect of life-long differences in brain health and mental stimulation - factors that represent possible ways to intervene earlier in life to reduce the changes of Alzheimer's in old age.

Knowing Genetic Risk May Not Increase Anxiety
Scott Roberts, Ph.D., and Robert C. Green, M.D., M.P.H., of Boston University School of Medicine, studied 162 adult children of people with Alzheimer's to assess the psychological impact of a genetic risk assessment program where genetic counselors provided participants with information about their lifetime risk of developing Alzheimer's. In this randomized trial, one group received risk assessment based upon age, sex and family history. In the other group, APOE genotype was also disclosed, including whether or not individuals carried the APOE-e4 gene that raises risk of Alzheimer's but does not guarantee that one will develop the disease.

Roberts and colleagues found that, for the vast majority of participants, disclosure of risk, including APOE disclosure, did not increase anxiety about developing Alzheimer's disease. However, those who tested positive for the e4 gene were more likely than others to report increased anxiety.

In open-ended discussions following disclosure, many study participants reported that their concerns about personal risk were much less prominent than the challenges of caregiving and coping with existing health problems.

Green, senior study author, commented, "This study is a first step toward showing that genetic risk information for Alzheimer's can be communicated safely and effectively. As treatments are developed that prevent or delay Alzheimer's, determining who is at higher risk will become more important."

"Though contrary to common wisdom, it turns out that, in circumstances that included appropriate counseling and education, learning about genetic risk for Alzheimer's did not generally increase people's anxiety," added William Thies, Ph.D., vice president, Medical & Scientific Affairs for the Alzheimer's Association. "This suggests that wider use of genetic counseling may be a useful tool in enabling people to know their situation and plan for the future."

The 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association, is the largest gathering of Alzheimer researchers in history. More than 4,500 scientists from around the world will present and discuss the findings of 2,000 studies showcasing the newest treatment advances in Alzheimer's disease and steps toward prevention. ICAD will be held July 17-22, 2004, at the Pennsylvania Convention Center in Philadelphia, Pennsylvania.
The Alzheimer's Association is the world leader in Alzheimer research and support. Having awarded more than $165 million to nearly 1,400 projects, the Alzheimer's Association is the largest private funder of Alzheimer research. To sustain the rapid progress, the Association calls for $1 billion in annual federal funding for Alzheimer research. For more information about Alzheimer's disease, visit or call 800-272-3900.

· Brenda Plassman - Alzheimer's Disease in the NAS-NRC Twin Registry of WWII Veterans (P4-137)
· Scott Roberts - How Does Genetic Testing Affect Anxiety about Developing AD? Findings from a Randomized Clinical Trial (P4-121)
· Margaret Gatz - Genetic Effects Do Not Account for the Relationship between Education and Dementia (P3-156)

Alzheimer's Association

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