Thursday, January 14, 2010

Small Head Circumference as Risk Factor for Alzheimer’s Disease

The size of the skull is fixed by age 7. Brain size approximates the head size until old age, when it begins to shrink. Some evidence has reported an association between small head size (and therefore less brain volume) and Alzheimer's disease. Nevertheless, other studies have found no association between a small head size and Alzheimer's disease.

Some experts suggest that the relationship observed in other research may simply be due to social and economic factors, such as malnutrition or low birth weight, which have been associated with both Alzheimer's disease and small head size. Small head size independent of other factors, they argue, does not pose a higher risk for either Alzheimer's disease or low intelligence.

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University of South Florida Research
According to researchers of University of South Florida (2001), the size of a person's head may be indeed one risk factor for Alzheimer's disease. People with a gene predisposing them to Alzheimer's who also have small heads were 14 times as likely to develop the disease than people without that gene variant and with larger heads.

The researchers believe people with smaller brains may be less able to compensate for the brain cell damage that is a hallmark of Alzheimer's disease, so symptoms like memory loss occur earlier in these people. But still this idea is debatable.

To test the theory, Borenstein Graves and her colleagues followed 1,700 healthy Americans age 60 or older for an average of about four years. During that time, 50 people developed Alzheimer's disease. The researchers measured the circumference of people's heads around the eyebrows and across the widest part of the skull. According to a study, participants with the smallest head measurements were slightly more likely to develop Alzheimer's than the people with the larger heads.

People with a gene variant called alipoprotein E 4 or ApoE4, a known risk factor for the disease, were 4.8 times more likely to be diagnosed with Alzheimer's. Alzheimer's developed most often among people with the ApoE4 gene variant and a small head circumference.

According to her head circumference probably does not influence the pathology (the underlying biological damage) of Alzheimer's, but is a mitigating factor in the development of symptoms. While brain growth is controlled in part by genetics, it also may be influenced by nutrition, infection, family size, and birth order. This study is not enough to definitively link smaller head size with an increased risk of Alzheimer's.

"Head circumference probably doesn't influence the pathology (the underlying biological damage) of Alzheimer's, but is a mitigating factor in the development of symptoms," Graves said. While brain growth is controlled in part by genetics, it also may be influenced by nutrition, infection, family size, and birth order, she said.

This study is not enough to definitively link smaller head size with an increased risk of Alzheimer's, said Neill Graff-Radford, chair of the department of neurology at the Mayo Clinic in Jacksonville, Fla. For one thing, a relatively small number of people developed Alzheimer's. Also, the study also shows "smaller head size is linked with older age, female gender, and less education," Radford said.

Previous studies have suggested people who have more education tend to be resistant to Alzheimer's disease, while women are more susceptible than are men. Increasing age probably is the biggest risk factor for Alzheimer's, while poor nutrition among children might explain their smaller heads, Radford said. "While it is plausible that head size might be related to Alzheimer's disease," he said, "it's still far from proven." "The question of brain reserve remains an open question," said Bill Thies, vice president for medical and scientific research at the Chicago-based Alzheimer's Association. "While head circumference may, long term, give us a better idea who should get preventive medicine, we don't have any such medicine available right now."

Chonnam National University Hospital Research
Community residents aged 65 or over (n = 916) within a defined geographic area of South Korea were screened clinically for dementia and dementia subtypes. Data on anthropometric measures (head circumference and leg length), demographics (age, gender), apolipoprotein E, and early life environment (birth order, number of siblings, parental occupation, area of residence, education) were gathered. Reproductive history was also ascertained in women.

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Both smaller head circumference and shorter leg length were associated with increased age, rural residence in childhood and lower education. After adjustment for these factors, they were both independently associated with Alzheimer's disease but only in women. Reasons for gender differences in associations require clarification but, for this population and age group, may include preferential treatment of male children in Korea.

The studies about the relationship between brain and head size and the development of dementia has a pretty long history, for its linkage to the “brain reserve theory” developed by Katzman. In this theory the onset of dementia is related to the brain (size) and cognitive reserve (education). The head circumference is well related to the brain volume, and both are smaller in women, so head size may be a “natural” predisposing factor for dementia in the female gender. But caution is needed when taking such conclusions. At first the findings of the Korean researchers must be considered: height and head size are strongly related, but are also independent factors for dementia and both may reflect a poorer childhood condition. Also lower education, a well known risk factor for dementia, may be due to the social condition and other data suggest an important correlation between head size and education. In particular data coming from the “Nun study” examined deeply this association, and found that it was strong in those who were destined to develop AD, those who carried apoE4 genotype and those who fulfilled neuropathologic criteria for AD. These findings are partially consistent with other studies that demonstrate an increased risk effect of the ApoE4 genotype in presence of smaller head circumference, with a younger age of onset of the disease. All these data may support the “brain reserve” theory: education for the cognitive reserve, apoE4 for the genetic reserve, head circumference for the brain/neurons reserve.

On the other hand we know that social condition can affect at least in part body size and education, and that female gender can sum up a smaller congenital size, a lower education and, at least in some developing countries, less nutrition in childhood, so to have a diminished brain reserve because of both biological and social conditions. These conditions might be a major contribution to the high presence of Alzheimer disease among women.

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