Brain Size Linked to Risk of Dementia, Study Finds : Health: The results suggest that the causes of Alzheimer’s disease may occur in infancy, not in old age.
People with below-average head size have as much as 18 times the normal risk of developing dementia caused by Alzheimer’s and other diseases, Washington state researchers have found.
The findings suggest that such individuals do not have enough brain cells in reserve to offset the loss of cells caused by aging and neurological diseases, said epidemiologist Amy B. Graves of Battelle Pacific Northwest Laboratories in Seattle. When such losses do occur, the brains of people with smaller than average heads are more likely to contain fewer cells than are necessary for coherent thought.
The new results suggest that the most important causes of Alzheimer’s may not occur late in life, as most scientists now believe, but at the very earliest stages of development, a conclusion that could have profound implications for efforts to prevent such disorders.
Graves’ findings are based on a study of 1,458 Japanese Americans that is to be presented at the upcoming Fourth International Conference on Alzheimer’s Disease and Related Disorders. The results are supported by at least two other studies previously published or now in press.
Although small head size can be genetic in origin, the most common causes are the mother’s smoking and drug use during pregnancy and nutritional deficiencies during pregnancy and in the baby’s first two years of life, the periods when brain cells are actively growing. “If we are going to invest money in preventing Alzheimer’s disease, we may want to invest it not among the elderly but at the other end of the age spectrum,” said Dr. James A. Mortimer of the Veterans Affairs Medical Center in Minneapolis. “It will be a very long-term investment, but it may prove to be the only effective way to do it.”
Graves’ study “does raise very interesting questions about the link between brain size and dementia,” said Dr. Peter Schofield of Columbia University. It is impressive because of the large number of people studied, he noted, but still more studies are necessary to confirm the results.
Dementia is a jumbling of thought processes that leaves the victim forgetful and confused, a condition that is often called senility. Although it has a variety of causes, the two most common are strokes and Alzheimer’s disease.
Previous work has shown that key areas of the human brain must have a minimum number of cells, called the threshold, to prevent dementia, Graves said. An average-size brain can afford to lose up to 70% of the cells it had during childhood in regions of the brain that control thought processes, such as the hippocampus.
After the first two or three years of life, no new brain cells are formed and those present die off at a more or less constant rate, unless the rate is accelerated by disease or injury. “If everybody lived long enough, everyone would become demented,” Graves said, but for many that might mean living to 120.
By that reasoning, the more brain cells a person has to begin with, the longer it will take for the number of cells to fall below the threshold. Head size is generally considered to be a rough indicator of brain size.
The Battelle research was carried out as part of an international study to compare the incidence of dementia, including Alzheimer’s, in Japanese Americans in Seattle and Honolulu and Japanese in Hiroshima, Japan. The goal is to help determine the relative influence of genetics and environment in strokes and Alzheimer’s disease.
In the study, Graves and her colleagues measured the head circumference of 1,458 people over the age of 65 and correlated it with their performance on a widely used diagnostic test for dementia. Those with the smallest circumference, about 21 inches or less, were 18 times as likely to be demented as those with a circumference of 23 inches or greater. In general, women’s heads are smaller, Mortimer said, but there is evidence that their brain cells may be packed more densely, which would offset the size difference.
Graves’ finding is buttressed by related studies. In a study of nursing home residents, Dr. Robert Katzman of UC San Diego first determined who was demented and then autopsied the brains after death. He found that people with dementia were most likely to have the smallest brains. In an as-yet-unpublished study, Schofield of Columbia has correlated the age of onset of Alzheimer’s disease in 28 patients with the size of their brains as determined by a CAT scan. He found that the larger the brain size, the older the patient was at diagnosis. He concluded that those with the largest brains could afford to lose more brain cells before dementia occurred.
The researchers cautioned that not everyone with a small head develops dementia. “The density of brain cells could be just as important as the overall size of the brain,” Mortimer said. Studies are under way now to determine if that is the case, he added.
