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Gene Linked to Accelerated Brain Aging in Healthy Adults

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By studying a chemical marker in the brain that reflects the health of brain tissue, researchers at Duke University Medical Center have found new clues about why some people experience more rapid age-related brain changes than others. Their findings were presented at the 15th annual meeting of the American Association for Geriatric Psychiatry.

The researchers have found an association between nerve cell changes connected with aging, and the presence of a gene known as apolipoprotein E4 (APOE4). This gene is carried by approximately 25 percent of the population and has been linked to increased risk of Alzheimer’s disease, cardiovascular disease, and memory loss from head injury or bypass surgery.

Although the signs of age-related memory loss are widely recognized, researchers are still unsure why some elderly adults retain strong mental capacity well into their 90s while others fall into progressive decline or dementia.

“The frontal lobe is the site where the earliest and most consistent effects of aging occur in the brain,” said P. Murali Doraiswamy, M.D., a psychiatrist at Duke and lead researcher on the study. “Virtually every mental symptom of normal aging results from decline in frontal lobe functions. When we examined this vital area of the brain by following a particular genetic marker, we found a single gene variation that can result in significant nerve cell changes associated with aging. Of the people we studied, those who carried the APOE4 gene experienced a more rapid loss of nerve cell functioning.”

In other words, those with the gene showed signs of aging faster than those without the gene.

Doraiswamy’s team measured levels of N-acetylspartate (NAA), a brain chemical known to be closely associated to nerve cells and mental functions. This chemical is primarily found inside nerve cells within the brain, and signals the health of a nerve cell.

“It is generally accepted that dying nerve cells have lower levels of NAA but little is known about the chemical’s role in a particular disease,” said Doraiswamy. “It’s what we call a surrogate marker.”

The researchers were able to detect nerve cell changes associated with aging by using magnetic resonance spectroscopy (MRS). MRS uses magnetic fields and radio waves to detect subtle changes in specific nerve cell chemicals to determine the cells’ health, damage, and loss of function.

Using MRS in the baseline study, the researchers compared the level of NAA in the brains of 165 healthy study participants with ages from 55 to 85. Of these, 84 participants were postmenopausal women and 81 were men.

The subjects were divided into two groups based on whether they were carriers of the APOE4 gene. After undergoing MRS both groups were administered a battery of memory tests to obtain their NAA and cognitive levels. After two years, a subset of the participants was studied again with memory tests.

The researchers found that those with lower NAA levels at the beginning of the study had greater loss of short-term memory after two years. Thus, the researchers concluded that the brains of those who carry the APOE4 gene show greater deterioration than those who do not.

“This is an important finding in the study of aging. I believe it will lead to a greater understanding of age-related memory loss and hopefully, one day, to ways of keeping our brains sharper, longer,” noted Doraiswamy.

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