CHICAGO – More pregnancies and a longer span of reproductive years appear to confer some level of protection against dementia, suggesting that lifetime estrogen exposure may be an important modulator of long-term cognitive health.
The study, presented at the Alzheimer’s Association International Conference, is the first to examine this question in a large cohort, comprising more than 14,500 women with up to 50 years of follow-up data. It is one of the first explorations in a renewed interest in the link between hormones and cognition, said Suzanne Craft, PhD, who moderated a press briefing on the topic.
“WHI [Women’s Heath Initiative] had a completely chilling effect on research into estrogen and cognition completely,” Dr. Craft of Wake Forest University, Winston-Salem, N.C., said in an interview. “Many well-regarded researchers simply couldn’t get funding and had to close their programs and move on to other areas. But now I think the pendulum is slowly moving back. It’s clear that something is going on, that there is a link. I’m glad we’re starting to explore this again.”
The investigation of women’s total reproductive experience affects dementia risk found several intriguing associations, said Paola Gilsanz, ScD, of Kaiser Permanente, Oakland, Calif. Earlier age of menarche, later menopause, and more completed pregnancies all independently reduced the risk of dementia in women.
Her study comprised 14,595 women, all members of the Kaiser Permanente health care database. All of them had completed a comprehensive health checkup sometime between 1964 and 1973, when they were 40-55 years old. 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 group (68%) was white, but 16% were black, 6% Asian, and 5% Hispanic. Dr. Gilsanz looked at rates of dementia during 1996-2017, when the women were 62-86 years old.
A multivariate regression model controlled for age, race, education, midlife health issues (hypertension, smoking, and body mass index), hysterectomy, and late-life health issues (stroke, heart failure, and diabetes).
Half of the cohort (50%) had at least three children, and 75% had experienced at least one miscarriage. The average age at menarche was 13 years, and the average age at last natural menstrual period was 47 years. This equated to an average reproductive period of 34 years.
At the end of follow-up, 36% of the cohort had developed some type of dementia.
Women with at least three children were 12% less likely to develop dementia, compared with those with one child (hazard ratio, 0.88). The association remained significant even after researchers controlled for age, race, educational level, and hysterectomy.
Miscarriages also influenced the risk of dementia. Those who didn’t report one were 20% less likely to develop dementia than were those who had experienced at least one (HR, 0.81). The benefit of no miscarriage was even greater among women with at least three children, conferring a 28% reduced risk (HR, 0.72).
A shortened reproductive period increased the risk of dementia. Those who experienced menarche at 16 years or older had a 31% increased risk of dementia (HR, 1.31), and those who experienced their last period at age 45 or younger faced a 28% greater risk (HR, 1.28). Each additional year of reproductive capability was associated with a 2% decreased risk (HR, 0.98).