Women represent nearly two-thirds of Americans living with Alzheimer’s disease, and scientists are just beginning to try to figure out why.
The conventional wisdom has held that women are more likely to be diagnosed with Alzheimer’s because they live longer than men, on average, and had fewer educational opportunities — shown to protect against dementia — decades ago. However, a small but growing body of research suggests that there’s more to the story.
Three studies presented in July 2015 at the Alzheimer’s Association International Conference in Washington, D.C., highlighted the greater vulnerability of women’s brains:
- Researchers found that memory and thinking skills in women with mild cognitive impairment (MCI) declined twice as quickly as they did in men. MCI refers to a slight but measurable decline in cognitive abilities, which include memory and thinking skills. People with MCI can still live independently, but they have a greater risk of developing Alzheimer’s or other types of dementia.
- A study at Oregon Health & Science University suggested that older women have a higher risk of experiencing cognitive dysfunction after undergoing surgery with general anesthesia than older men do. In addition, among people with post-operative cognitive dysfunction, the study found that women declined more rapidly than men.
- A third study examined levels of amyloid plaques, one of the hallmarks of Alzheimer’s, in the brains of people across a range of cognitive ability, from normal to Alzheimer’s disease. Women were found to have more amyloid plaque in their brains than men of the same age and same cognitive ability, said Duygu Tosun, of the University of California, San Francisco. This was the case regardless of whether the women carried the APOE e4 gene, which is second only to getting older as the most important risk factor for Alzheimer’s.
“There may be a greater biological vulnerability” to Alzheimer’s in women, says Katherine Lin, a Duke University undergraduate from Seattle who conducted the MCI study. Lin used data from the Alzheimer’s Disease Neuroimaging Initiative to look at how the cognitive abilities of about 400 people with MCI changed over a period as long as eight years.
Even after accounting for factors that could influence the rate of decline in MCI, such as age and education, Lin found that women’s cognitive abilities worsened more quickly than men’s.
Among people 71 and older, an estimated 16 percent of women have Alzheimer’s and other dementias, compared with 11 percent of men, according to the Alzheimer’s Association.
Research has not yet pinpointed a particular reason why women might be more susceptible to dementia, but candidates include genetics, estrogen and the rate at which their brain cells die, Lin and Dr. P. Murali Doraiswamy, director of the Neurocognitive Disorders Program at Duke, wrote in an opinion piece published in January 2015.
Some speculate that taking estrogen in the early years of menopause might protect the brain; taking it later might have the opposite effect.
— Katherine Lin, Duke University researcher
Studies of estrogen’s effect on the brain have had mixed results. On the one hand, the hormone appears to possibly reduce amyloid accumulation, so the sharp decline in estrogen after menopause might increase women’s risk of Alzheimer’s, Lin says.
On the other hand, research has found that taking estrogen after menopause raises women’s risk of MCI and Alzheimer’s disease. Some scientists speculate that taking estrogen in the early years of menopause might protect the brain, while taking it later might have the opposite effect, Lin says.
Anesthesia a Possible Culprit
In her study of post-operative cognitive dysfunction (POCD), Dr. Katie Schenning, an anesthesiologist at the Oregon Health & Science University in Portland, found that after receiving general anesthesia, women’s brains shrunk more than men’s and their cognitive abilities declined more rapidly. Schenning based her analysis on an average of seven years of follow-up data for each patient.
“Most people do just fine” after general anesthesia, Schenning says, and in those who develop POCD, the condition is usually temporary. But older adults have a greater risk for long-term POCD following general anesthesia, although the symptoms are sometimes mistakenly attributed to normal aging, she says.
Whether POCD is a forerunner of Alzheimer’s or other types of dementia is not clear, says Schenning, calling for more research.
While doctors don’t know how to prevent POCD, minimizing exposure to general anesthesia “could be a really great idea,” Schenning says.
Further Research Warranted
Clearly, many questions remain about why women might be more susceptible to Alzheimer’s disease than men. The Alzheimer’s Association recently convened a “think tank” of a dozen researchers to examine how biological, genetic, hormonal and lifestyle differences might make women more vulnerable.
“The conclusion we came to is that there’s enough to support an inquiry in this,” says Maria Carrillo, chief science officer at the Alzheimer’s Association.
To help answer questions about sex differences, the Alzheimer’s Association has launched the Women’s Alzheimer’s Research Initiative to raise $5 million for research grants. The initiative will begin accepting applications for funding from researchers worldwide this fall, Carrillo says.
Lin may be only 20-years-old, but already, she says, she’s known several people with Alzheimer’s.
“I’ve gotten this sense of how devastating this disease is and how much we don’t know,” she notes.
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