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Among the great mysteries -- and horrible injustices -- of aging is that dementia strikes more women than men. No one knows why exactly. For years, scientists suspected that the culprit is estrogen. Implicated in memory formation, estrogen levels plummet after women reach menopause.
But here's the catch. If low estrogen levels are behind age-related dementia in women, then why did a massive study by the National Institute of Health find that women who had hormone replacement therapy (HRT) were no less likely to experience cognitive decline than women who didn't have it?
Because not all estrogens are created equal, nor are all brains. Motherhood may be the missing link.
This comes from an intriguing new study by Cindy Barha and Liisa Galea, neuroscientists at the University of British Columbia's Brain Research Center. Barha and Galea knew that the female brain is highly plastic; it literally restructures itself in the course of pregnancy and caring for a baby. They were curious about whether motherhood might alter the brain in a way that protects against dementia under certain conditions.
One way to explore this is to study middle-aged rats that are genetically identical in every way with the exception of their reproductive lives. The scientists divided the rats into groups -- virgins and mothers -- and injected each with a form of estrogen: estradiol or estrone (the form in HRT). Later, they looked at the rats' brain tissue to see whether new cells had formed -- a process called neurogenesis -- in the hippocampus where memories are formed. These new cells may reduce the risk of dementia.
It's interesting, this contest between middle-aged virgins and mothers. Compared to virgin rats who had been injected with estrogens (and mothers who hadn't), the middle-aged mothers that took the hormone replacement therapy grew significantly more new cells in the memory region of their brains when exposed to the estrogens (especially a combination of estrone and 17a-estradiol). The hormones helped the mothers' minds to remain malleable.
Why did the mothers have a seeming advantage? Anther mystery -- which Barha and Galea say may be related to an enhanced ability of mothers' hippocampuses, even late in life, to respond to estrogens. Such responsiveness may come from hormone exposure during pregnancy or afterward, or enrichment from the experience of mothering.
Interestingly, estradiol's effect on the brain is mediated by BDNF (brain derived neurotrophic factor levels), which may be higher in mothers than in those who have not given birth. The researchers note that BDNF may help explain an assocation between high levels of estrogen exposure across a lifespan and a decreased risk of cognitive decline and Alzheimer's disease. Among rats, those who have been mothers have a reduced age-related decline in spatial memory and other cognitive decline.
The scientists conclude:
Therefore previous reproductive experience, which is associated with altered hormone exposure and greater enrichment, can result in higher levels of plasticity in the middle-aged brain and may protect the brain from the deleterious effects of aging in females.
But there's a very real caveat. Applied to humans, these findings are still highly speculative. First, the boost would depend on a woman taking hormone replacement therapy, which remains controversial due to its connection with breast cancer. (Why hasn't HRT been shown to improve cognition thus far? It may because a combination of estrone and 17a-estradiol is much more effective than the current regimen of estrone and progestin.)
More importantly, there is no guarantee that new neurons will improve a person's ability to learn and remember or decrease the risk of cognitive decline. As Barha and Galea warn, all that new growth might even lead to a sort of jungle effect if not properly integrated. There are clearly other factors that determine what properties these new cells will have as they mature. Do some mothers put their new neurons to use more effectively than others? No one knows whether or how, but the question is fascinating. (More research is underway in Barha and Galea's lab.)
What's clear is that motherhood results in permanent changes in the brain. Will we mothers someday benefit cognitively more than childless women from new hormonal therapies? There's a chance. Wouldn't it be marvelous if a cognitive boost later in life would compensate for all the sleepless nights now?
*If you like this blog, click here for previous posts. If you wish, check out my new book, Do Chocolate Lovers Have Sweeter Babies?: The Surprising Science of Pregnancy.
