Alzheimer’s disease is the sixth leading cause of death in the United States, and nearly two-thirds of Americans with the disease are women.
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"Age is the greatest predictor of Alzheimer's, so for a long time, there was this notion that women are at higher risk only because they live longer," Pauline Maki, professor at University of Illinois, told CBS Chicago. "No one was paying attention to what was going on in the female brain throughout a woman's life."
Maki and her colleagues were among many who presented their new research at the 2018 Alzheimer's Association International Conference, held this week in Chicago, suggesting that women's reproductive history may help determine their risk of developing Alzheimer's.
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For one of the presentations, scientists from Kaiser Permanente examined the reproductive history of 14,595 women aged 40-55 who were Kaiser Permanente members between 1954 and 1973 and still members between 1996 and 2017. It was essential that all women included were Kaiser Permanente members for most of their lives because researchers did not have to rely on the patients’ memory — they had reliable questionnaires and medical records. Approximately 32 percent of the women were nonwhite.
The records documented several factors, including:
- Education
- Race
- Midlife health status
- When each woman began menstruating
- When she went into menopause
- Number of pregnancies
- Number of miscarriages
- Number of reproductive years
- Dementia diagnosis
- Later-life chronic conditions (heart failure, diabetes)
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Key findings
According to the Kaiser Permanente study, the largest of its kind in the U.S., women who started their first menstrual cycle after turning age 16 were 31 percent more likely to develop cognitive problems than women who began by age 13.
Women who gave birth to three or more children had a 12 percent lower risk of developing dementia in later life compared to women with fewer children.
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Women who reported miscarriages had an 8 percent higher risk of the disease with each miscarriage. In fact, compared with women who never miscarried, women with three or more miscarriages had a 47 percent higher risk.
"In the '60s and '70s, we knew much less about pregnancy, about medical conditions that might be manifest," another study author, Rachel Whitmer, told the Washington Post, cautioning against the idea that miscarriages themselves as contributing to Alzheimer's.
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Fewer fertile years (only 21 to 30) yielded a 33 percent higher risk of developing dementia.
And those who stopped menstruating at age 45 or earlier also had a higher risk of developing the neurodegenerative disease than women who stopped menstruating later.
Study author Paula Gilsanz told the Post that "one hypothesized reason is that it is cumulative exposure to estrogen across the life course," that may protect against the disease. Most scientists theorize that the biggest estrogen boost occurs around a woman's third trimester.
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Other research
But another study out of the University of California, Los Angeles, which examined births, miscarriages and abortions of 133 English women aged 70-100, found that the association between pregnancies and lower risk of dementia may actually be due to immune changes from the first trimester.
In fact, study author Molly Fox told the Washington Post that a woman who experienced 20 percent more first trimesters had a 30 percent lower risk of developing Alzheimer’s compared to “another otherwise identical woman.” Fox and her team found no association between number of trimesters and Alzheimer’s risk.
“If estrogen were explaining the relationship, the most potent predictor would be how many times you experienced that late surge in hormone level,” she said. “We hope that it will spark a little bit more of a comprehensive conversation . . . beyond the one topic that has dominated the debate so far.”
Other scientists from the Gleason of the Wisconsin Alzheimer’s Disease Research Center examined how hormone therapy among diabetic women in their late 60s and 70s significantly increases risk of the disease, whereas there was no harm or benefit for non-diabetic women or women who begin therapy in their early 50s.
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