Around two-thirds of people suffering from Alzheimer's disease are women but there has been a surprising lack of research into what could be causing such a stark sex-specific difference in the disease. Several new studies into reproductive history and dementia risk in women have now revealed contradictory results, suggesting pregnancy may have some kind of effect on dementia risk later in life.

The observation that women seem to develop Alzheimer's disease more often than men is not an especially new one, and the prevailing hypothesis is that it's simply due to the fact that on average women live longer than men, hence they have more opportunity to develop the condition with old age. But some scientists are now suggesting that this is an overly simplistic explanation and the real reasons behind the sex-discrepancy could be much more complicated.

The largest recent new study using long-term data from members of regional Kaiser Permanente Medical Groups examined records from nearly 15,000 women and found that subjects with three or more children were 12 percent less likely to develop dementia compared to women with just one child. The study also found that each reported case of miscarriage correlated with a 9 percent increase in dementia risk.

The duration of a woman's reproductive period was also studied in correlation with dementia risk, and it was found that the longer the reproductive period the less chance a woman had of developing dementia. Women with reproductive periods lasting between 21 and 30 years were found to have a 33 percent higher chance of developing dementia compared to women with reproductive periods of 30 to 44 years.

Adding some confusion to the mix was another recently released study that came to the exact opposite conclusion. This study, led by Seoul National University, looked at 3,500 subjects and found that women with five or more children were 70 percent more likely to develop Alzheimer's disease compared to women with one to four children. The study also found that women suffering from a miscarriage or incomplete pregnancy had a significantly lower risk of developing Alzheimer's compared to women who completed their pregnancies.

The contradictory results are undeniably frustrating but they do highlight the vital need for more research into this area. Both of these studies do suggest that there is some kind of connection between pregnancy and dementia risk, but unpacking exactly what mechanism could be causing this will take a great deal more work.

Ki Woong Kim, a neuropsychiatrist at Seoul National University and author of the second smaller study, suggests that there may be an ideal level of estrogen that confers a protective effect on women, but when these levels rise too high they could be detrimental to long-term cognition.

"It's possible that the modestly raised levels of estrogen in the first trimester of pregnancy are within the optimal range for protecting thinking skills," says Kim.

But the solution doesn't seem as simple as using some kind of hormone replacement therapy to reduce dementia risk. An influential study from 15 years ago suggested estrogen plus progestin therapy in menopausal women over the age of 65 actually increased a woman's risk of dementia. This study resulted in an increased level of caution in generally administering hormone therapy to older women.

Another new study into hormone therapy and cognition is now suggesting that administering estrogen to younger women during menopause and throughout their 50s may actually be beneficial. These results simply add weight to the complexity of hormonal transitions that can occur over the course a woman's life. In the case of estrogen supplementation, timing may be everything.

Rachel Whitmer, from the University of California Davis and co-author of the new larger-scale reproductive study, suggests it is vital that future research starts to actively engage in better understanding what could be mechanistically causing these interactions between reproductive events and brain health. Despite the contradictions between the findings in these recent studies, there is undeniably something going on that demands further investigation.

"It's a call to action for the field to take seriously why women specifically are at higher risk of developing dementia, and what it is about the female brain and the hormonal milieu over the life course that sets the brain up for higher or lower risk," says Whitmer.

The results of these new studies were presented at the recent Alzheimer's Association International Conference (AAIC) 2018 in Chicago.