Small Head Size and Genes are Factors in Alzheimer’s Disease

The risk of developing Alzheimer’s disease may be increased for people with small head sizes, and for those who also carry an Alzheimer’s-related gene. This is according to a study published in the October 23 issue of Neurology, the scientific journal of the American Academy of Neurology.

People with small head size and the gene variant apolipoprotein E e4 (ApoE e4) are 14 times more likely to develop Alzheimer’s disease than people without that combination. Having a small head size without the gene did not significantly increase the risk of developing Alzheimer’s. This result adds weight to the theory that having a large “brain reserve” protects against Alzheimer’s.

“The theory is that the symptoms appear when the loss of brain cells goes below a critical threshold of brain reserve,” said Amy Borenstein Graves, PhD, of the University of South Florida in Tampa, who conducted the study with researchers at the University of Washington in Seattle. “People with ApoE e4 are likely to have more rapid brain cell damage. Those with large brain reserves may have the same changes in their brains, but they don’t show symptoms of the disease until much later.”

The study involved 1,869 healthy Japanese Americans age 65 and older in King County, Washington. Study participants were divided into three groups, based on head circumference. Only the group with the smallest head circumference (less than 21.4 inches), and ApoE e-4, had a significantly greater risk of Alzheimer’s. The study participants were followed for an average of 3.8 years. During that time, 59 people developed Alzheimer’s disease. Those who developed Alzheimer’s were also older, less educated, shorter, lighter and had lower estimated verbal IQ (intelligence quotient) scores than those who did not develop Alzheimer’s during the study period.

Borenstein Graves said that while brain growth is controlled in part by genetics, it may also be influenced by factors during the first 10 years of life, such as malnutrition, poverty, infection, parental occupation and educational status, family size and birth order.

Later in life, factors such as higher education and income and mental and physical exercise may play a role in delaying the onset of Alzheimer’s disease.

“It’s interesting to speculate on whether we could prevent this disease if we could systematically boost our brain reserves throughout life,” Borenstein Graves said. “In our study 18 percent of the risk of Alzheimer’s was attributable solely to small head size. So if it were possible to increase brain reserve through prevention of brain damage that occurs across the life span, nearly 20 percent of the disease among these individuals might be preventable.”

Borenstein Graves said a limitation of the study is its sample population of only Japanese Americans, which makes it difficult to apply the results to the general population.

“However, several studies with other populations have shown a relationship between head circumference and cognition and rates of developing Alzheimer’s,” she said.

The study was supported by the National Institute on Aging.

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