Women's Risk of Alzheimer's Disease and Cognitive Decline Linked to Gene Sequence

SAN DIEGO—Women who have a particular gene sequence are at a higher risk of developing cognitive impairment and Alzheimer’s disease, according to a study from researchers at UCSF and the Veterans Affairs Medical Center (SFVAMC).

These inherited sequences, which create small differences in the receptor that binds estrogen, were linked with increased risk of Alzheimer’s or of declining performance on tests of cognitive function over several years, said lead author Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC, and UCSF assistant professor of psychiatry, neurology and epidemiology.

“In this study of older women, there wasn’t that big a difference in the initial cognitive scores.  But over time, the women with these certain sequences had much more cognitive impairment.  And they also had a much higher risk of being diagnosed with Alzheimer’s disease,” she said.

The study conducted by Yaffe and her colleagues at UCSF and Axys Pharmaceuticals, was presented here at the Society for Neuroscience Annual Meeting today, November 14.

The researchers focused on two regions of the estrogen receptor gene that vary greatly from person to person.  These gene regions, generally known as polymorphisms, had previously been linked to risks of osteoporosis, endometriosis and breast cancer, Yaffe said.

The study, which followed more than 2,800 women over roughly seven years, found that women with the high risk polymorphism were about 30 to 40 percent more likely to either suffer a major decline in test scores, or be diagnosed with Alzheimer’s disease.

So far, there’s no clear explanation for how these very small differences in the estrogen receptor gene actually influence the fate of women’s brains, Yaffe said.  A few studies suggest that the polymorphisms may change the function of the receptor.  “We really need more research in this area,” she said.

The estrogen receptor gene is only one of many that are likely to influence the risk of Alzheimer’s disease, Yaffe said.  “We know about several genes that are linked to Alzheimer’s or appear to be, but it’s estimated that we have only found about 50 percent of these genetic risk factors,” she said.

Previous studies have shown that estrogen and its receptors play a major role in women’s brains.  “We know there are estrogen receptors throughout the brain, particularly in the areas involved in learning and memory,” Yaffe said. Also, estrogen therapy after menopause appears to protect women from cognitive decline, she said.

Yaffe’s co-author’s on the study included: Li-Yung Lui, MS, and Katie Stone, PhD, researchers in UCSF’s department of epidemiology and biostatistics; Deborah Grady, MD, professor and vice chair of epidemiology and biostatistics at UCSF, and a physician at SFVAMC; and Philip Morin, PhD, at Axys Pharmaceuticals in La Jolla, Calif.

The study was supported by grants from the National Institutes of Health. \###