Women with a history of hypertensive disorders of pregnancy more likely to develop dementia

Hypertensive disorders of pregnancy (HDP) — conditions of high blood pressure including chronic/gestational hypertension and preeclampsia — have been strongly linked to heart disease in later life, but, before today, little research has connected these disorders with cognition. The key findings presented at AAIC 2022 include:

• Women with a history of HDP were more likely to develop vascular dementia — a decline in thinking skills caused by conditions that block or reduce blood flow to the brain — later in life, compared to women with non-hypertensive pregnancies.
• Experience of HDP, specifically high blood pressure during pregnancy, was associated with white matter pathology, a predictor of accelerated cognitive decline, 15 years after pregnancy.
• Women with a history of severe preeclampsia had significantly higher levels of beta amyloid, an Alzheimer's-related brain change, as measured in blood, compared to women with non-hypertensive pregnancies.

Affecting nearly 1 in 7 hospital deliveries, HDP is one of the leading causes of morbidity and mortality in birthing persons and fetuses worldwide. These conditions impact Black, Latino, Asian/Pacific Islander and Native American populations at disproportionately high rates.

This is among the first longitudinal data linking hypertensive disorders of pregnancy with dementia in a large study cohort. Considering the serious short- and long-term implications of HDP, early detection and treatment are vital to protect both the pregnant person and baby."

Claire Sexton, D.Phil., senior director of scientific programs and outreach at the Alzheimer's Association

"These data illuminate the importance of prenatal care and monitoring the long-term health of pregnant people," said Sexton. "Those who experience any changes with their memory and cognition should have a discussion with their health care provider."

HDP associated with higher risk of vascular dementia

To explore the association between HDP and later-life dementia, Karen Schliep, Ph.D., MSPH, assistant professor in family and preventive medicine at University of Utah Health, and colleagues, performed a retrospective cohort study among 59,668 women who had experienced a pregnancy.

Women with a history of HDP had a 1.37 times higher adjusted risk of all-cause dementia after taking into account maternal age, year of childbirth and parity than women with non-hypertensive pregnancies. HDP was associated with a 1.64 times higher risk of vascular dementia and 1.49 times higher risk of other related dementia, but not Alzheimer's disease. Gestational hypertension and preeclampsia/eclampsia showed similar magnitudes in risk for vascular dementia.

"Our results confirm previous findings that preeclampsia is most strongly associated with vascular dementia compared to Alzheimer's or other types of dementia," said Schliep. "They further suggest that vascular dementia risk may be just as high for women with a history of gestational hypertension as for preeclampsia."

HDP associated with white matter pathology 15 years post-pregnancy

Given the well-established association between HDP and long-term cerebrovascular health, Rowina Hussainali, M.Sc., a doctoral student in epidemiology and obstetrics and gynecology at the Erasmus MC Medical Center, Netherlands, and colleagues, aimed to examine the associations between HDP and markers of vascular brain pathology 15 years after pregnancy.

The researchers examined 538 women, 445 with a non-hypertensive pregnancy and 93 with HDP, from the Generation R study. Pregnant women with an expected delivery date between April 2002 and January 2006 were included. Fifteen years later, some of these women underwent magnetic resonance imaging to assess brain tissue volumes as well as other markers that could indicate pathology.

Hussainali and team found women with prior HDP had 38% more white matter pathology (indicative of the wearing away of brain tissue) compared to women with previous non-hypertensive pregnancy. This association was driven by women with gestational hypertension, who had 48% more white matter pathology compared to women with previous normotensive pregnancy. No differences were found with other markers of brain pathology, such as infarcts or cerebral microbleeds. The development of chronic hypertension after pregnancy strengthened this result, especially in women with previous gestational hypertension.

"These data clearly indicate that a history of HDP was associated with more damage to the brain 15 years after pregnancy — damage that could have lasting impacts on cognition," said Hussainali. "Women with a history of HDP should be evaluated and treated early for hypertension and other cardiovascular risk factors."

Preeclampsia linked to increased markers of brain inflammation

Preeclampsia is a severe hypertensive disorder of pregnancy that affects up to 5-8% of pregnancies. A large body of data indicates that women with a history of preeclampsia have an accumulation of health risk factors later in life, including heart disease. As severe preeclampsia has been associated with the highest risks for cerebrovascular disease, Sonja Suvakov, M.D., Ph.D., postdoctoral research fellow and assistant professor of medicine at Mayo Clinic, and team, explored whether vesicles — small fluid-filled pouches — released from brain cells would be detectable in women years after their affected pregnancies.

The researchers found that women with a history of severe preeclampsia had significantly higher concentrations of extracellular vesicles positive for amyloid beta, a protein that makes up one of the hallmark brain lesions of Alzheimer's. They also found a significant increase of extracellular vesicles positive for markers of brain endothelium damage and inflammation. Similarly, circulating levels of beta amyloid were also increased.

"These findings indicate that women with a history of preeclampsia have increased levels of markers of neurovascular damage which may negatively impact their cognitive skills," said Suvakov. "Further research is required to fully understand the neurodegenerative and cognitive risks that a history of hypertensive disorders confers on women throughout life."