Hat Size Can Help Predict Alzheimer's Risk

Study says combine of head circumference and a key gene can foretell brain disorder

MONDAY, Oct. 22, 2001 (HealthDayNews) -- Could hat size help point to who'll get Alzheimer's disease? A new study by Florida researchers says yes.

Scientists say the combination of a small head and versions of a gene linked to Alzheimer's disease strongly predict early onset of the devastating brain disorder. However, the researchers say, small head size alone doesn't increase the odds of getting the malady.

"We don't think that head circumference is a risk factor for the pathology [of Alzheimer's], but rather it is an enabling risk factor" that may hasten the disease, says Amy Borenstein Graves, an epidemiologist at the University of South Florida and lead author of the study, which appears in the Oct. 23 issue of the journal Neurology.

Graves and her colleagues had earlier shown that immigrant Japanese Alzheimer's patients with small skull circumference tend to lose more cognitive ability with age than those with broader noggins. "We saw that the relationship between cognitive test scores and head circumference was very, very strong in the Alzheimer's group but not in [those without the condition]. If you're going to get the disease, small head size created more impairment."

The reason, Graves suspects, is that a smaller head holds fewer brain cells, so there's less on "reserve" to lose to erosion from disease. When that reserve gets built up or how it's kept stocked isn't entirely clear, she adds. But research suggests that the various stages of life are important in different ways.

In early childhood, for example, the brain is busy building itself, making connections between neurons and establishing the density of those cells. In adolescence, with its years of intensive education, these connections are further cemented, but can wane if they're not continually reinforced by mental stimulation in young adulthood, middle age, and beyond. That's the "use it or lose it" concept of neurology that has become a recent mantra of sound mental aging.

"If you have more neurons at some point, you have a bigger head," Graves say. "But the density of connections is also important. That's why keeping your brain active in later life" can guard against dementia.

The new study followed the same group of elderly Japanese immigrants, now living in the Seattle area, for an average of almost four years. Fifty-nine of the approximately 1,900 immigrants showed signs of probable Alzheimer's disease, which is conclusively diagnosed only by autopsy. Graves' team broke the people into groups based on the size of their head, as well as whether they had versions of a gene called APOE, which is known to raise the risk of Alzheimer's.

APOE is short for apolipoprotein E, a molecule involved in the production of sticky plaques in the brain, and the e4 form of the gene is a powerful predictor of Alzheimer's risk. People with one or two copies of the e4 form of APOE were found to be at five times risk of developing the disorder as those without a copy, the researchers found.

Although people within the smallest third of head size -- less than 21.4 inches around, compared with an average of about 22.5 inches -- seemed more likely to develop Alzheimer's during the study, that risk wasn't statistically significant, Graves says. But when low head size was coupled with APOE e4, the odds of developing the disease jumped by a factor of 14.

The risk of developing Alzheimer's during the study period was also higher for people who were older when it began, who were shorter and lighter, who had less of an education, and who scored lower on verbal intelligence tests.

Graves sees larger head size -- a sign of brain reserve -- as a brake on Alzheimer's for those with genes or a history of trauma (such as a head injury) that predispose them to develop the disease. "You can kind of hang on until you go over the waterfall. I think that's what's happening here. It's sort of like a threshold."

Once the reserve is exhausted, dementia can descend. But for some people with the largest reserves, she says, the signs of Alzheimer's may never crop up before death from other causes.

Dr. Lon White, an epidemiologist who studies brain disorders at the Pacific Health Research Institute in Honolulu, says the latest findings require "sort of a shift in the way we think about disease in older people."

"Vulnerability," White says, "can be as potent a predictor of a specific disease as is a cause of that disease."

In this case, vulnerability is malnutrition or other factors during early childhood development, which prevent the brain from becoming as large as it's genetically programmed to grow. Because the skull molds to fit the matter inside, "in most people the head is as big as the brain makes it be," he says.

The unanswered question, White adds, is what happens to the neurons of a "disadvantaged brain." How many are there -- as opposed to those in one of full size -- and how are they organized?

Whatever the case, he says, it's important to know that skull size isn't a useful predictor of intelligence. "We have much more reserve than what we need. But in Alzheimer's, that reserve, which falls for decades, finally crosses the threshold."

Equally important, just like getting plenty of calcium can delay or prevent the onset of osteoporosis later in life, slowing the dwindle of one's brain reserve can stave off Alzheimer's, he says.

What To Do

Four million Americans, and 10 percent of those over 65, suffer from Alzheimer's disease, which has no cure. For more on the condition, try the Alzheimer's Association or the Alzheimer's Disease Education and Referral Center.

Alzheimer's Disease International has information for caregivers.

SOURCES: Interviews with Amy Borenstein Graves, Ph.D., professor of epidemiology, University of South Florida, Tampa; Lon White, M.D., senior neuroepidemiologist, Pacific Health Research Institute, Honolulu; Oct. 23, 2001, Neurology
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