Could pregnancy protect women against developing dementia? That’s one hypothesis scientists offered at the Alzheimer’s Association International Conference in Chicago on Monday. According to the scientists’ research, women who had three or more children had a 12 percent lower risk of dementia later in life than those with fewer children.

That was one of several findings that indicate there are associations between a woman’s reproductive history and her risk of developing the disease. The study, the largest of its kind in the United States, specifically found links between a woman’s number of children, miscarriages, cumulative months of pregnancy and years between first menstrual period and menopause — and her risk of developing dementia.

But that was just one of several studies presented at the conference. Others showed that women’s immune function may affect Alzheimer’s; another suggested that women’s use of hormone therapy does not necessarily heighten their risk; and yet another offered an explanation as to why the majority of American dementia patients are women, not men.

A woman’s reproductive history

In a study of 14,595 long-term Kaiser Permanente members, researchers looked at the reproductive history of women who were 40 to 55 between 1964 and 1973 and were still members between 1996 and 2017. The study was uniquely diverse, spanning a range of education levels and including 32 percent nonwhite subjects.

Among the study’s findings:

• Women who had had three or more children had a 12 percent lower risk of dementia in later life than those with fewer children.

• Women who didn’t get their first period until age 16 or 17 had a 31 percent higher risk of dementia than those who began menstruating at 13. Women who stopped menstruating at age 45 or earlier had a 28 percent higher risk of dementia than women who stopped menstruating after age 45.

Why would a woman’s menstrual cycle increase her risk of getting dementia? Exposure to estrogen could be the answer, said Paula Gilsanz, a staff scientist at the division of research at Kaiser Permanente Northern California and an author of the study.

“One hypothesized reason is that it is cumulative exposure to estrogen across the life course,” which may protect against the disease, Gilsanz said.

• Those who had reported miscarriages had an 8 percent higher risk of dementia with each report of a miscarriage.

Rachel Whitmer, a professor of epidemiology at the University of California at Davis’s school of medicine and the study’s other author, cautioned against seeing miscarriages themselves as contributing to Alzheimer’s. Whatever conditions caused the miscarriages could also have put women at higher risk for the disease, she said.

“We don’t know why they had miscarriages,” she said. “A plausible explanation is they had some pregnancy-related health issues” such as hypertension or gestational diabetes. “In the ’60s and ’70s, we knew much less about pregnancy, about medical conditions that might be manifest.”

Can estrogen really protect against Alzheimer’s?

Estrogen may not be the only reason pregnancy seems to protect against Alzheimer’s. Another may lie in immune function, according to a University of California at Los Angeles study presented at the conference. It found that women who spend more cumulative months pregnant — especially in the first trimester — have a lower risk of developing dementia. For each additional month pregnant, the risk went down by 5.5 percent.

Although the dominant theory for the lower risk associated with pregnancies has credited the estrogen boosts that happen largely in the third trimester, the UCLA study suggests the benefit may lie in the immune system changes that take place in the first trimester. During the first trimester, a woman experiences increases in a special type of immune cell that suppresses inflammation and continues to rise after pregnancy; Alzheimer’s patients have fewer of these cells.

The UCLA study found that the lower risk was associated with the cumulative number of first trimesters, but that the number of third trimesters had no significant effect.

“If estrogen were explaining the relationship, the most potent predictor would be how many times you experienced that late surge in hormone level,” said Molly Fox, the study’s author and an assistant professor in UCLA’s departments of anthropology and psychiatry and behavioral sciences. “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.”

Does hormone therapy increase risk?

Research at the conference also included updates to the associations between hormone therapy and Alzheimer’s risk. Previous studies had suggested that women who start taking hormones in their late 60s and 70s have a higher rate of cognitive decline, a paper out of the University of Wisconsin school of medicine and public health found that risk to be elevated specifically for women with diabetes.

For non-diabetic women and for women who started the therapy in their early 50s, there was no cognitive harm or benefit associated with taking the hormones, the new research found. And women receiving an oral form of the therapy demonstrated improved mood and reductions in anxiety and depression.

Previous findings had sometimes contradicted each other, leading women to swing between embracing or avoiding hormone therapy based on fears of cognitive effects, said Carey Gleason, an associate professor of medicine at Wisconsin.

The new findings should reassure “women who are worried they are hurting their brains either in the moment or down the road,” Gleason said. Women need to talk with their doctors about their personal risk profiles, but for a woman using hormone therapy to help with menopause-related issues related to sleep, sexual function, mood and bone health, “at least she can put into the algorithm the information that she’s not hurting her cognition if she opts to use it.”

Why dementia differs in men and women

It’s been known that more American women than men have Alzheimer’s. The prevailing explanation has been that women live longer and that it is a disease associated with aging — but a study out of the University of Illinois at Chicago has found that the disparity may lie in diagnosing Alzheimer’s.

The study used the Alzheimer’s Disease Neuroimaging Initiative, a large longitudinal study in the United States, to look at brain imaging of 764 women and 941 men at different stages of diagnosis.

Among women and men who showed similar moderate disease levels in neuroimaging, women had better verbal memory performance in clinical tests, though this advantage disappeared as the disease advanced.

Women perform better on such verbal tests throughout their life span, so men are more often diagnosed with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s. But while the standard measures for diagnosing aMCI account for age and education, they do not account for gender. So doctors might miss diagnosing women in early stages of dementia because their better verbal memory can mask the disease, according to the study. They might also over-diagnose aMCI in men, since the assessment standards are based on average performance by both women and men.

If the standards were adjusted to account for gender, some men could avoid the stress of being wrongly diagnosed with aMCI, Maki said. And some women could benefit from knowing sooner, both in terms of planning and in being able to benefit from FDA-approved medications that work best in the early stages of dementia.

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