Women’s brains appear to be more vulnerable to the degenerative effects of Alzheimer’s disease than men’s, according to a trio of new studies that could explain why women make up more than two-thirds of all diagnosed Alzheimer’s cases in the United States
In one study, researchers from Duke University Medical Center found that women who display the early signs of mental decline that can precede Alzheimer’s disease deteriorate faster than men with the same condition. Another study revealed that women’s brains tend to accumulate higher levels of amyloid, an abnormal protein that plays a key role in triggering Alzheimer’s. And a third study found that women are more likely than men to develop long-term impairments in memory and cognitive abilities after undergoing surgery with general anesthesia.
The new research, presented this week at the Alzheimer’s Association International Conference (AAIC) in Washington, D.C., lends additional support to the view that women run a higher risk than men of developing Alzheimer’s disease and may be more vulnerable to its damaging effects once the illness gets going. The findings also challenge the notion that more women have Alzheimer’s simply because they tend to outlive men, said Dr. Kristine Yaffe, an Alzheimer’s researcher at the University of California, San Francisco.
“It’s not just that women are living to be older,” Dr. Yaffe told the Associated Press. “There’s something else going on in terms of the biology, the environment, for women compared to men that may make them at greater risk, or if they have some symptoms, change the progression.”
Over 5 million people in the United States currently live with Alzheimer’s disease and one in three seniors dies with the disease or another form of dementia, according to the Alzheimer’s Association. The number of Americans living with Alzheimer’s is projected to triple by 2050, and women are facing an increasingly disproportionate burden.
Currently, women make up about two-thirds of all Alzheimer’s cases. However, that proportion is rapidly shifting: Among those newly diagnosed with Alzheimer’s, up to 75 percent are women, said Dean Hartley, director of science initiatives at the Alzheimer’s Association. By age 65, women without the disease have more than a one in six chance of developing Alzheimer’s during the remainder of their lives, compared with a one in 11 chance for men. Women also comprise the vast majority of Alzheimer’s caregivers.
Faster disease progression
The new research on women with mild cognitive impairment was part of a large ongoing study called the Alzheimer’s Disease Neuroimaging Initiative. Researchers studied up to eight years of records on about 400 men and women in that study who had mild cognitive impairment (MCI), a condition that often leads to Alzheimer’s.
The results were striking: cognitive abilities of women in the study with MCI declined twice as fast as men’s – a result that was statistically significant.
“Our findings suggest that men and women at risk for Alzheimer’s may be having two very different experiences,” said study co-author Dr. Katherine Amy Lin, part of a team at Duke University Medical Center. “Our analyses show that women with mild memory impairments deteriorate at much faster rates than men in both cognitive and functional abilities.”
Increased risk of postoperative brain dysfunction
In a separate study, researchers led by Dr. Katie Schenning of the Oregon Health & Science University tracked records of more than 500 participants in two long-term studies of cognitive aging, which included a battery of brain tests. About 180 participants had undergone surgical procedures involving general anesthesia.
After following the participants for seven years, researchers found that the participants who had undergone surgery with general anesthesia declined faster on measures of cognitive ability, overall functioning, and even brain shrinkage than those who hadn’t had surgery. However, women deteriorated at a significantly faster rate than men, the researchers said.
“This is one of the first studies to suggest that among older adults, women are at a higher risk for postoperative brain dysfunction than men,” Dr. Schenning said in a press release.
More amyloid accumulation
Another study presented at the Alzheimer’s meeting used PET scanning to measure levels of amyloid in about 1,000 people, including many with cognitive impairment or Alzheimer’s disease. Amyloid is the substance that forms sticky plaques in the brains of Alzheimer’s patients, which typically start to accumulate long before the appearance of symptoms such as memory loss and confusion.
There was a clear difference between men and women, regardless of their age, said Dr. Michael Weiner of UCSF, the study’s senior author. “Overall, women have more amyloid than men,” which suggests they are at higher risk of developing Alzheimer’s, he told the Associated Press. This was found to be true even among the cognitively normal group.
The XX factor
What’s still not clear, researchers said, is why women’s brains are more vulnerable than men’s to Alzheimer’s and other memory problems. One possible explanation is that every cell in a woman’s body carries two X chromosomes, instead of an X and a Y. These double x chromosomes could be what’s putting women at a higher risk of developing dementia, according to research done back in 2009.
Published in the journal Nature Genetics, the study showed that women who inherited two copies of a variant in the PCDH11X gene, found on the X chromosome, were at a much higher risk of developing Alzheimer’s disease. Women with a variant on one of their two X chromosomes also had some increase in risk, as did men with the variant on their single X chromosome, but these effects were weaker than inheriting two variants, the study found.
“This is a very common genetic variant, and many women who had two copies of it did not have disease. But, overall, the odds were substantially greater that female patients with the disease did have two copies,” the study’s senior investigator, Steven Younki, of the Mayo Clinic, said in a press release at the time. The researchers described the sex-specific gene variant as one of the “stronger risk factors found to date.”
However, researchers say that other factors — such as stress, hormones, childbearing, sleep, diet, and exercise — likely also contribute to women’s heightened vulnerability. Additionally, said Dr. Lin, these latest findings “point to the possibility of as yet undiscovered sex-specific genetic or environmental risk factors that influence the speed of decline”.
If scientists can figure out the factors that account for women’s vulnerability to Alzheimer’s, they might be able to develop treatments that halt the process, Dr. Lin said. “Uncovering those factors should be a high priority for future research,” she added.
Despite the disproportionate burden shouldered by women, there has been relatively little sex-specific research in the area of Alzheimer’s disease. This is in part because of the widespread misconception that women’s heightened risk can be explained by their longer life expectancies, and in part because medical research has traditionally overlooked the need for sex-specific research. But in order to address the growing sex-based disparities in Alzheimer’s prevalence, severity and prognosis, researchers must first understand the reasons behind them.