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Pregnancy and Years of Reproductive Capability Are Associated With Dementia Risk

Miscarriages and age at menarche and menopause may influence the likelihood of dementia.


CHICAGO—More pregnancies and a longer span of reproductive years appear to protect women against dementia, according to a study presented at AAIC 2018. The results suggest that lifetime estrogen exposure may be an important modulator of long-term cognitive health.

Paola Gilsanz, ScD

The study by Paola Gilsanz, ScD, staff scientist at Kaiser Permanente in Oakland, California, and colleagues included more than 14,500 women and 50 years of follow-up data. Earlier age of menarche, later menopause, and more completed pregnancies all independently reduced the risk of dementia in women.

Reproductive Years

The researchers analyzed data from a cohort of 14,595 women in the Kaiser Permanente health care database. All of them had completed a comprehensive health checkup between 1964 and 1973 when they were ages 40 to 55. They reported their number of miscarriages, number of children, ages at first and last menstrual period, and the total number of years in their reproductive period. Most of the women in the group (68%) were white, but 16% were black, 6% Asian, and 5% Hispanic. Dr. Gilsanz looked at rates of dementia during 1996 to 2017, when the women were ages 62 to 86.

A multivariate regression model controlled for age, race, education, midlife health issues (eg, hypertension, smoking, and BMI), hysterectomy, and late-life health issues (eg, stroke, heart failure, and diabetes).

Half of the cohort had at least three children, and 75% had at least one miscarriage. The average age at menarche was 13, and the average age at last natural menstrual period was 47. This equated to an average reproductive period of 34 years.

At the end of follow-up, 36% of the cohort had developed dementia.

Women with at least three children were 12% less likely to develop dementia, compared with those with one child. The association remained significant even after researchers controlled for age, race, education, and hysterectomy.

Miscarriages also influenced the risk of dementia. Those who did not report a miscarriage were 20% less likely to develop dementia than were those who had experienced at least one miscarriage. The benefit of no miscarriage was greater among women with at least three children, conferring a 28% reduced risk.

A shorter reproductive period increased the risk of dementia. Those who experienced menarche at age 16 or older had a 31% increased risk of dementia, and those who experienced their last period at age 45 or younger had a 28% greater risk. Each additional year of reproductive capability was associated with a 2% decreased risk.

Women with between 21 and 30 reproductive years were 33% more likely to develop dementia than were those with longer reproductive periods.

Renewed Interest

“Reproductive events that signal different exposures to estrogen, like pregnancy and reproductive period, may play a role in modulating dementia risk,” Dr. Gilsanz said. “Women who are less likely to have a miscarriage may have different hormonal milieus that may be neuroprotective. Underlying health conditions increasing the risk of miscarriages may also elevate risk of dementia.”

Researchers are exploring the link between hormones and cognition with renewed interest, said Suzanne Craft, PhD, of Wake Forest University in Winston-Salem, North Carolina, who moderated a press briefing on the topic. The Women’s Heath Initiative study had a chilling effect on funding for this area of research, Dr. Craft said. “But now I think the pendulum is slowly moving back” toward supporting investigations of hormones and cognition. “It’s clear that something is going on, that there is a link. I am glad we are starting to explore this again.”

—Michele G. Sullivan

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