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CHICAGO -- Womens' reproductive history was significantly associated with their risk for dementia, researchers reported here.

In an analysis of nearly 15,000 women, various reproductive factors, including number of children, miscarriages, and age of menarche, were all associated with a women's risk for dementia later in life, according to Paola Gilsanz, ScD, of Kaiser Permanente Northern California Division of Research in Oakland, and Rachel Whitmer, PhD, of the University of California Davis.

"Our findings are consistent with estrogen possibly having a neuroprotective effect. Reproductive events that signal different exposures to estrogen may play a role in modulating dementia risk," Gilsanz explained to MedPage Today at the Alzheimer's Association International Conference. "For example, we found that each additional year in a woman's reproductive span, the number of years between age at first and last menstrual period, was associated with a 2% decrease in dementia risk."

She added that women in general have a much higher prevalence of dementia compared with men, yet the sex-specific risk factors for women are poorly understood.

"There is evidence that estrogen may be neuroprotective, but research looking at reproductive history across the life course has had inconsistent results. We conducted this study to better understand how aspects of women's reproductive history across the life course may be associated with their brain health."

Heather Snyder, PhD, senior director of medical and scientific operations for the Alzheimer's Association, said it's important to understand "what all of [linkages of reproductive health] might do and mean for brain health," she told MedPage Today. Snyder, who was not involved in the study, added that the mechanisms are not currently understood but "this really underscores that the biology of what's happening, what is it about a woman, about her body, that may impact her brain health."

All participants in the study by Gilsanz and colleagues were Kaiser Permanente Northern California members who were 40-55 years old in 1964-1973 and ages 62-86 in 1996. Reproductive history was self-reported by the participants, while dementia diagnoses were collected from electronic health records. A dementia diagnosis included Alzheimer's disease, vascular dementia, and non-specified forms of dementia.

Women who delivered three or more children had a 12% lower risk for dementia compared with women with only one child (HR 0.88, 95% CI 0.81-0.95). Even after adjustment for several factors such as accounting for possible differences in race, age, education, and hysterectomies, women with more children had a reduced risk for developing dementia compared to women with fewer children.

Furthermore, a history of miscarriages was tied to a higher risk for dementia, with each additional miscarriage tied to an 8% higher risk for dementia (adjusted HR 1.08, 95% CI 1.05-1.12). Women who experienced three or more miscarriages in their life saw a 47% higher risk for dementia versus women who never experienced a miscarriage (aHR 1.47, 95% CI 1.27-1.71).

In contrast, women who never reported a miscarriage had a 20% lower risk for dementia (HR 0.80, 95% CI 0.73-0.89). Women who never experienced a miscarriage and had three or more children saw an even lower risk for dementia, reduced by 28% compared with women who had at least one miscarriage (HR 0.72, 95% CI 0.62-0.83).

"This could be because women who are less likely to have a miscarriage may have different hormonal milieu that may be neuroprotective," Gilsanz suggested, adding how possible underlying health conditions tied to miscarriages may also increase dementia risk.

Women who experienced an early menarche - - specifically at age ≤9 years - - saw a slightly higher risk for dementia compared with women who experienced menarche between the ages of ages 10-13; however, this association wasn't statistically significant (aHR 1.40, 95% CI 0.83-2.37). Those who had a later menarche than average age (≥16) also saw a higher risk for dementia (HR 1.31, 95% CI 1.05-1.62).

Interestingly, women who had shorter windows of reproductive periods also saw a higher risk for dementia (reproductive periods of 21-30 years vs 39-44 years, HR 1.33, 95% CI 1.11-1.58).

"Our findings are consistent with estrogen playing a role in modulating dementia risk but we are not suggesting any direct clinical implications," Gilsanz emphasized. "It is important to put this research into context and acknowledge decreases in family size and improved screening practices for pregnancy-associated complications, such as pre-eclampsia, that have occurred since these data on reproductive history were collected in the 1960s and 1970s."

The study's observational nature was a limitation.

Some of the findings appear to conflict with those in a concerning pregnancy history and Alzheimer's disease. That analysis of two long-term prospective cohorts indicated that a history of incomplete pregnancies (e.g., miscarriage) was associated with markedly reduced risk for developing Alzheimer's. Moreover, women who carried five or more pregnancies to term had nearly doubled rates of Alzheimer's versus those with one to four.

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