Published on: May 18, 2020
by Women’s Brain Health Initiative:
Women are disproportionately affected by many brain disorders. For example, it is estimated that almost 70% of individuals diagnosed with Alzheimer’s disease are women. Women’s Brain Health Initiative and the Brain Canada Foundation have been advocating for the inclusion of women in research studies to help determine what is behind the sex differences in brain health and how that impacts potential treatment. Historically, research studies often included only male subjects, which kept research design and analysis less complicated.
Thankfully, there has been an increasing awareness in the research community of the importance of studying sex differences, and a corresponding increase in the inclusion of female subjects in studies.
However, in order to make substantial progress in the study of women’s health, researchers need to go even further and consider variables among women. In other words, while we do need to study what makes women and men different, we also need to study differences between women. For example, research suggests that there are brain health differences between women based on variables related to pregnancy (e.g. whether a woman has had a pregnancy, how many children she has had, and her age when she gave birth).
Dramatic changes occur in a woman’s body during pregnancy and into the postpartum, affecting her physiology (e.g. cardiac, immune, and metabolic function), as well as endocrinology (e.g. hormones). A woman’s estradiol and progesterone levels, for example, rise by up to 300-fold during the 40 weeks of pregnancy. It is therefore not surprising that such changes have an impact on a woman’s health – including her brain health – in the short-term.
But it may be surprising to some to learn that pregnancy also appears to have long-term impacts, affecting the brain and cognitive function into middle age and beyond.
Cognitive performance during pregnancy and postpartum
Many women notice cognitive changes during pregnancy, such as increased forgetfulness and distractibility, and difficulty thinking of words. But, are these subjective self-reports of change consistent with objectively-measured assessments of cognitive performance?
A recent review on the short- and long-term effects of pregnancy and motherhood on the brain was conducted by Dr. Duarte-Guterman and colleagues and published in 2019 in Frontiers in Neuroendocrinology. Dr. Paula Duarte-Guterman received a 2017 Alzheimer’s Association Research Fellowship, co-funded by the Brain Canada Foundation and Alzheimer’s Association, to explore the impact of pregnancy and motherhood on the brain to better understand the short- and long-term effects on cognition and brain health, including Alzheimer’s disease.
“Research findings have varied somewhat from study to study, but the latest meta-analyses on human cognition during pregnancy suggest that pregnant women do experience small, but significant, deficits in some aspects of cognitive function, namely, free recall, delayed free recall, working memory, and executive function,” said Dr. Duarte-Guterman, a postdoctoral research fellow in the laboratory of Dr. Liisa Galea at the University of British Columbia. “Interestingly, one aspect of memory – recognition memory – was found to improve slightly during pregnancy.”
What happens to a woman’s cognitive function in the postpartum period, after the baby is born? “Although research is more limited on this subject, the available evidence suggests cognitive deficits may be experienced in the early postpartum that are similar to what is experienced during pregnancy,” said Brain Canada-funded Dr. Duarte-Guterman. “In recent studies, the evidence suggests that in the period two to six months postpartum, executive function is enhanced in mothers compared to non-mothers.”
There are some surprising variables that seem to affect cognitive performance during pregnancy and postpartum, which may account for differences in cognitive function among pregnant women.
Together, the evidence collected to date in human studies suggests that “the effects of pregnancy on cognitive function may be subtle, but can be more pronounced in certain groups of women, including those experiencing depression and anxiety, those who have given birth before, and those who are carrying a female fetus,” summarized Dr. Duarte-Guterman.
Changes in brain volume during pregnancy and postpartum
Not only does a woman’s cognitive function change during pregnancy and the postpartum period, but the brain itself also physically changes.
Research conducted by Dr. Angela Oatridge and colleagues, published in 2002 in American Journal of Neuroradiology, found that a woman’s total brain volume decreases during pregnancy, reaching its smallest size at the time of childbirth and rebounding in size by six months after delivery. Later studies conducted by various researchers found that the changes in brain volume during postpartum differed depending on which brain structure was imaged.
For example, Dr. Pilyoung Kim and colleagues found that grey matter volume increased in areas involved in maternal behaviours and motivation – such as the amygdala, hypothalamus, and prefrontal cortex – during the first three to four months postpartum versus the first two to four weeks postpartum. These findings were published in 2010 in Behavioral Neuroscience.
Yet, when Dr. Elseline Hoekzema and colleagues compared brain images of women pre-conception versus postpartum, they found reductions in grey matter volumes in multiple areas postpartum, including the hippocampus. Additionally, most of the grey matter reductions noted at two months postpartum were still present two years after birth. These findings were published in 2016 in Nature Neuroscience.
Some parts of the brain shrink and others enlarge, at various points during pregnancy, early postpartum and beyond.
“The effects of pregnancy on brain matter volume remain understudied, but it is evident that the impacts are time- and brain region-dependent,” observed Dr. Duarte-Guterman.
Pregnancy’s long-term effects on cognitive performance
Research findings about the effect of pregnancy on cognitive performance later in life are inconsistent. Parity refers to the number of pregnancies a woman has experienced to 20 weeks or more of gestation, whether the baby was born alive or stillborn. Nulliparity (i.e. no pregnancies experienced beyond 20 weeks of gestation) and lower parity are associated with better cognitive function in later adulthood in some studies, but not in others.
The number of pregnancies experienced is not the only variable involved, though. There are other factors related to reproductive history and endogenous estrogens that appear to impact cognition over the long-term, including length of reproductive period (i.e. number of reproductive years), age at first and last pregnancy, and duration of breastfeeding.
“Multiple studies of older women have found that measures of higher endogenous estrogens – such as lower parity, longer reproductive period, and shorter breastfeeding period – are associated with better cognitive performance,” said Dr. Duarte-Guterman. “In other words, women who experience higher lifetime exposure to endogenous estrogens, regardless of what variable provided that higher exposure, seem to enjoy better cognitive function later in life. Estrogens appear to be neuroprotective.”
Reproductive history and long-term risk of brain disorders
Numerous studies have examined the impact of parity on the risk of brain disorders. “In our review, we found studies that showed amount of parity is positively associated with an increased risk of Alzheimer’s disease,” said Dr. Duarte-Guterman. “Grand multiparity – sometimes defined as having three or more children, sometimes five or more – has been linked to an increased risk of developing Alzheimer’s disease.”
Research has also found higher parity is associated with increased levels of hallmark changes in the brain associated with Alzheimer’s disease, as well as earlier onset of the disease.
“It’s important to note, though, that not all studies have found links between parity and increased risk of Alzheimer’s disease,” emphasized Dr. Duarte-Guterman. “It’s possible that genetics play a role, interacting with parity to influence risk of Alzheimer’s and timing of onset. This is something that I am currently investigating as part of a study funded by Brain Canada.” For more information about Dr. Duarte-Guterman’s research, visit: https://braincanada.ca/research-stories/the-effect-of-pregnancy-on-brain-aging-in-women/.
The more we know about the differences between women – whether due to differences in reproductive history, genetics, or other variables – the better. Findings from research like that conducted by Dr. Duarte-Guterman and others have important implications for the development of treatments. It is possible that unique treatments will be needed for various subsets of women as they may have varied responses depending on their unique health history and genetics.
“Further research is needed to unravel the specifics of what makes women unique from men, what makes women who’ve experienced pregnancy different from women who have not, and how to apply that knowledge to the development of treatments,” said Dr. Duarte-Guterman. “I’m very pleased to be a part of this important area of ongoing research.”
Source: MIND OVER MATTER V10
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