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Reproductive History Influences Women’s Dementia Risk

CHICAGO — A woman’s reproductive history influences her risk for dementia, new results from the first large-scale epidemiologic study to examine this issue show.

The investigators, led by Paola Gilsanz, ScD, staff scientist at Kaiser Permanente Northern California Division of Research in Oakland, found correlations between a woman’s dementia risk and the number of her children, as well as miscarriage, age at first menstrual period, age at natural menopause, and the number of years between first menstrual period and menopause.

“Women have substantially higher prevalence of dementia compared to men, but female sex-specific risk factors over the life course are not well understood,” said Gilsanz.

The findings were presented here on July 23 at a press briefing at the Alzheimer‘s Association International Conference (AAIC) 2018.

Age at Menstruation

Using the Kaiser Permanente database, the researchers evaluated data for 14,595 women (68% white) who were between 40 and 55 years of age in 1964 to 1973.

They had detailed information on the women’s reproductive history as well as dementia diagnoses and late-life health events from medical records reviewed from 1996 to 2017. Thirty-six percent of the women developed dementia during this follow-up period.

Women with three or more children (50%) had a 12% lower risk of developing dementia compared to women with only one child (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 – 0.95). The results held up after accounting for additional mid- and late-life risk factors, such as body mass index and stroke history.

Three-quarters of the women had had at least one miscarriage. Women who had not had a miscarriage were at 20% lower risk for dementia compared to women who had, after accounting for possible differences in race, age, education, hysterectomies, and mid- and late-life health conditions (HR, 0.80; 95% CI, 0.73 – 0.89).

Among women with three or more children, those who did not report a miscarriage had a 28% lower risk for dementia compared to women who reported at least one miscarriage (HR, 0.72; 95% CI, 0.62 – 0.83) .

“Women who are less likely to have a miscarriage may have different hormonal milieu that may be neuroprotective. Underlying health conditions increasing the risk of miscarriages may also elevate risk of dementia,” Gilsanz said.

The number of years between the first menstrual period and natural menopause also seemed to matter. The average length of reproductive period for women in the cohort was 34 years.

Compared to women with reproductive periods of 38 to 44 years, those with reproductive periods of 21 to 30 years had a 33% higher risk for dementia after adjusting for demographics (HR, 1.33; 95% CI, 1.11 – 1.58). Each additional year of a woman’s reproductive period was associated with a 2% decrease in dementia risk (HR, 0.98; 95% CI, 0.97 – 1.00).

Women who experienced their first menstrual period at age 16 years or older were at 31% greater risk for dementia than those who reported having their first menstrual period at age 13 (HR, 1.31; 95% CI, 1.05 – 1.62).

With regard to menopause history, women who experienced natural menopause at age 45 years or younger had a 28% greater dementia risk after adjusting for demographics than their peers who experienced natural menopause after age 45 (HR, 1.28; 95% CI, 1.14 – 1.44).

This study “contributes to a growing body of evidence that exposure to different forms of estrogen across the life course impacts brain health,” said Gilsanz.

More Than Just Hormones

Commenting on the findings for Medscape Medical News, Michelle Mielke, PhD, of the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said hormonal changes during pregnancy may be one possible explanation.

However, she said, “There are a whole host of other potential explanations, including vascular and immunological changes in pregnancy. There really has been much research so far looking at what those mechanisms might be.”

Heather Snyder, PhD, senior director of medical and scientific operations at the Alzheimer‘s Association, said this is “an important study and area of research.”

“What is it about pregnancy or our reproductive health that might be impacting our risk in later life? I don’t think we know,” she acknowledged. “It could be the hormone pathways or other changes that happen in our immune system during pregnancy, or it may be better nutrition during pregnancy.”

Cognitive reserve might also play a role, because women with many children are “likely multitasking quite a bit, which may help build more cognitive reserve,” Snyder noted.

The study was funded by the National Institute on Aging. Dr Gilsanz has disclosed no relevant financial relationships. Dr Mielke has served as a consultant to Lysosomal Therapeutics Inc and Eli Lilly Co and receives unrestricted research grants from Biogen, Lundbeck, and Roche. Dr Snyder has disclosed no relevant financial relationships.

Alzheimer‘s Association International Conference (AAIC) 2018. Abstract P3-587, presented July 23, 2018.

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