Women who gave birth to more than five children were at a higher risk of developing Alzheimer’s disease, compared to those with fewer or no children, according to an analysis of two large longitudinal studies published in Neurology on July 18.
An estimated 5.7 million Americans have Alzheimer’s disease and two-thirds are women. Several theories exist to explain the gender gap, including that women outlive men. Another theory implicates pregnancy, an experience unique to women.
Hormones such as estrogen, which fluctuate during pregnancy, could be neuroprotective or neurotoxic, depending on the concentration.
To investigate the relationship between pregnancy history and the risk of Alzheimer’s disease, a team of researchers from Seoul National University in South Korea pooled data from two population-based studies: the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) in Greece. The combined studies included 3,549 women with an average age of about 71. At the time of assessment, women who took hormone-replacement therapy and those with a hysterectomy, or surgery to remove the ovaries, were excluded.
On average, participants completed the Mini-Mental State Examination (MMSE) 46 years after their first childbirth to measure cognitive impairment. Based on the women’s scores, the researchers determined that 118 women developed Alzheimer’s disease and 896 women developed mild cognitive impairment, a precursor to Alzheimer’s.
Women who gave birth to five or more children demonstrated a 70 percent higher risk of developing Alzheimer’s disease than those with fewer children. Of the 716 women with five or more children, 59 developed Alzheimer’s disease, compared to 53 of the 2,751 women with fewer children. The results were unchanged even after researchers accounted for other medical conditions, use of hormone replacement therapy, and breastfeeding.
Women who had an incomplete pregnancy, whether because of a miscarriage or an abortion, showed half the risk of developing Alzheimer’s disease compared to their counterparts. Of the 2,375 women who had incomplete pregnancies, 47 developed Alzheimer’s disease, compared to 71 of 1,174 women who never experienced an incomplete pregnancy.
Moreover, women with five or more children scored lower on tests of memory and thinking skills compared to those with fewer children. On a test where 30 points is the maximum score, scores of 24 or more indicate normal thinking skills; scores of 19 to 23 indicate mild cognitive problems. On average, women who gave birth to five or more children had scores of 22 points, compared to almost 26 points for women with one to four childbirths.
In comparison, women with one or more incomplete pregnancies scored higher than women with no complete pregnancies, regardless of how many children they had. Those with five or more children, with no history of incomplete pregnancies, averaged 22 points. Women with one or more incomplete pregnancies averaged more than 23 points.
"Estrogen levels double by the eighth week of pregnancy before climbing up to 40 times the normal peak level," said study author Ki Woong Kim, MD, PhD, of Seoul National University in Seoul, South Korea, in a statement.
"If these results are confirmed in other populations, it is possible that these findings could lead to the development of hormone-based preventive strategies for Alzheimer's disease based on the hormonal changes in the first trimester of pregnancy."
The researchers highlighted a potential link between how much a woman was exposed to hormones and her risk for Alzheimer’s disease. The study suggests estrogen and other hormones may influence the risk of Alzheimer’s, but the underlying mechanisms remain unclear.
Further research is warranted to take into account the physical and hormonal changes a woman goes through during pregnancy and how those changes may affect brain health.