DIMENSIONS Spring 2000


by Cheryl Dawes

Although the most significant risk factor for Alzheimer's disease is advanced age, a recent University of Washington study suggests that childhood and adolescent environmental factors may also contribute to risk for developing the disease. In a study of more than 750 older adults enrolled in the Group Health Cooperative in Seattle, Dr. Victoria Moceri, research scientist in the Department of Epidemiology, and her colleagues found an association between two early-life factors and later development of Alzheimer's disease.

The idea of a relationship between the brain's early development and cognitive decline in later life was first proposed more than 60 years ago. Since that time, researchers studying growth and development patterns of the brain have found associations between dementia and growth measures such as height, head circumference and linguistic ability assessed at age 18. "All these studies add a piece of information to the puzzle of Alzheimer's disease but many more studies are needed to understand the full picture," says Moceri. "Our study looked at socioeconomic factors which influence growth and development to further understand the association of early life and Alzheimer's disease."

Conditions in the environment in which children are raised, such as nutrition, play a role in how they grow and develop. Research has demonstrated that the effects of early-life environment on growth and maturation in children are linked to adult chronic diseases such as heart disease and stroke. Similarly, growth and maturation of the brain-development of the connections between brain cells that enable brain function-may be an early-life link to Alzheimer's disease.

The areas of the brain that continue to mature throughout adolescence are the same areas that show the first signs of AD, notes Moceri. Animal studies and studies in human children show that malnutrition can adversely affect brain maturation and lead to less efficient though normal brain function. This reduced efficiency probably has little effect until exacerbated by the aging process, she says.

Moceri and her colleagues hypothesized that if deficient maturation is associated with a less developed brain, then measures of early growth affected by environmental conditions could be associated with Alzheimer's disease. To test this hypothesis she and her colleagues, Drs. Walter Kukull, Irvin Emanuel, Gerald van Belle and Eric Larson, compared aspects of early life in 393 Alzheimer's disease patients (cases) and in 377 age and gender-matched individuals who did not have dementia (controls).

These early-life variables included the mother's age at the time of study subject's birth, the subject's birth order among his or her siblings, the number of siblings and the area of residence before age 18, whether farm, rural, urban or suburban. All of these variables relate to growth and development. However, only two of them, area of residence and number of siblings, were associated with increased risk for Alzheimer's disease.

More controls than cases grew up in the suburbs, an area of residence usually corresponding to mid to upper socioeconomic levels during the early 1900s. The researchers speculate that children growing up in the suburbs were more likely to have better nutrition and less exposure to infectious disease than their counterparts living in densely populated urban areas. Such benefits would foster growth and development.

The researchers also found that growing up in a family with five or more siblings increased the risk of developing AD by 39 percent and that the risk increased directly with the number of siblings. Compared with families of five or fewer siblings, they found that coming from a family of seven to nine siblings almost doubled the risk. The number of siblings in a family also relates to economics, Moceri notes. The larger the family, the further available resources must stretch.

The factors that did not have a statistical association with Alzheimer's disease-mother's age and birth order-are related to the birth environment, explains Moceri. In contrast, the number of siblings and area of residence are factors related to growth and development throughout childhood and adolescence. "Seeing an association between number of siblings and area of residence with Alzheimer's disease and not seeing an association with mother's age and birth order may suggest that growth and development of the brain during later childhood and adolescence could be more important than growth of the brain at birth," she says.

Moceri and her colleagues found no effect from other factors that might confound the relationship between the early-life variables they identified and Alzheimer's disease. The researchers collected information about study participants' education level and whether they carried APOE E4, a gene associated with susceptibility to Alzheimer's. They controlled for these factors in their analysis and found that the associations of number of siblings and area of residence held up.

However, there are limitations to this type of study, starting with the difficulty of obtaining early-life information from older adults. "We are looking at factors that occurred 50 to 70 years ago," notes Moceri. "Because Alzheimer's disease affects memory, we can't ask the person with the disease for information. We must ask a family member or someone else who knows the person. As a result, some of the information is unknown or not accurate, which makes it harder to understand the relationship between these factors and the disease."

More research is needed to completely characterize the relationship between growth, development of the brain and Alzheimer's disease, says Moceri. "Having many siblings and growing up on a farm does not mean a person will get Alzheimer's disease. There are probably many different causes of the disease along with genetic factors. One cause will not be unique to every person. Results of the current study point to the importance of continued investigation of how the brain develops through adolescence."

Moceri plans to continue exploring the relationship. "My goal is to find better ways to measure the early-life environment and rates of childhood growth and development of people who are now elderly so we can more fully assess the early-life association with Alzheimer's disease and how genetic factors interact with the early-life environment."

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