Published February 14, 2013
Women who carry a well-known genetic risk factor for Alzheimer's disease showed signs of more rapid aging in their body's cells than women who didn't have it, according to a new study.
The study, by researchers at Harvard and Stanford universities, may be a "critical link in our understanding of the role that APOE-e4 plays in the development of the disease," said Elizabeth Edgerly, chief program officer for the Northern California and Northern Nevada Chapter of The Alzheimer's Association. Edgerly was not involved in the study.
About 25 to 30 percent of the population carries at least one copy of APOE-e4 (each person inherits two copies, one from each parent). Forty percent of people with Alzheimer's disease are carriers.
Over the course of two years, researchers studied 63 post-menopausal women — their average age was 58 — who had been voluntarily taking hormone replacement therapy, either estrogen alone or estrogen plus progesterone, for at least one year. All the women were deemed at risk for Alzheimer's disease due to a family history of the condition. However, only 24 of the women were APOE-e4 carriers. All but one study participant was white.
At the study's start, baseline length measurements of each woman's telomeres were taken. A telomere is a "cap" on the end of each chromosome that protects the genes on the chromosome from deterioration. Every time a cell replicates, its telomeres shorten a little bit. That shortening has been associated with a number of aging-related diseases, including Alzheimer's.
Half of the women were then randomly assigned to stop taking hormone therapy while half stayed on it. After two years, the researchers measured the length of each woman's telomeres again.
The researchers found that women who were APOE-e4 carriers were six times more likely than non-carriers to exhibit obvious telomere shortening once they stopped taking hormones. In fact, APOE-e4 carriers experienced more rapid telomere shortening than non-carriers, suggesting that their cells had aged the equivalent of seven to 14 years over the course of the two-year study. But APOE-e4 carriers who remained on hormone replacement therapy showed no evidence of telomere shortening during that time.
"Our results suggest that for women with this genetic variant, hormone replacement therapy may reduce the risk for cellular aging, which may also reduce their risk of dementia," said Heather Kenna, a doctoral student in clinical psychology at Stanford University and one of the study authors. "However, we cannot make recommendations on hormone therapy from this one study alone or suggest that it will decrease risk of dementia."
It's unclear whether the protective effect the researchers saw was due to hormone replacement therapy or some other factor. For instance, there may be something different about women who chose to initiate hormone replacement therapy: they may live a healthier lifestyle or have a higher socioeconomic status, among other factors. Thus, they may not be representative of all women, Edgerly said.
"This is a promising first step, but future studies should focus on tracking larger numbers of women over a longer period of time," she said.
The current study was not designed to examine the differences between the two hormone therapy options — estrogen or estrogen plus progesterone, according to the study authors. The Women's Health Initiative, which started in 1991 and ended in 2010, found that estrogen plus progestin therapy offered no protection against mild cognitive impairment in women over age 65. In fact, women who took the hormones had an increased risk of dementia. Results from a study examining the effects of estrogen-only therapy on cognition are not yet available. The WHI involved more than 160,000 generally healthy postmenopausal women.
While genetic testing for the APOE-e4 gene type is commercially available, neither Kenna nor Edgerly recommend it for most people. Individuals with or without a family history of Alzheimer's who want to be tested for the gene must first undergo counseling so they are informed about the risks and benefits of finding out if they carry the gene.
"Knowing you have the e4 gene is a powerful piece of information — one that may have repercussions for employment and long-term-care insurance, not to mention the psychological burden of knowing you are at a much higher risk for a disease with no known cure," Edgerly said.
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