Hypertensive disorders of pregnancy: A risk factor for dementia?

Individuals with a history of hypertensive disorders of pregnancy (HDP) appear to have an increased risk of developing dementia, particularly vascular dementia, according to a study presented at AAIC 2022.

“Our results confirm previous findings that preeclampsia is most strongly associated with vascular dementia compared to Alzheimer’s or other types of dementia,” said study author Associate Professor Karen Schliep from the University of Utah Health, Salt Lake City, Utah, US.

“They further suggest that vascular dementia risk may be just as high for women with a history of gestational hypertension as for preeclampsia,” she added.

The retrospective study involved 59,668 women who had ≥1 singleton pregnancy between 1939 and 2019 in Utah, US. Of these, 19,989 women had a history of HDP, the most common being preeclampsia or eclampsia (65.9 percent) and gestational hypertension (33.5 percent). They were matched (one to two) based on 5-year age group, year of delivery, and parity at time of pregnancy with women who had not experienced HDP (n=39,679).

The women were followed up between 1979 and 2019, with dementia diagnosed in 4.1 percent. Twenty-four percent of these were Alzheimer’s disease, 6 percent vascular dementia, and 70 percent other or unspecified dementia.

Compared with women without a history of HDP, women with a history of preeclampsia or eclampsia had an elevated risk of developing all-cause dementia (hazard ratio [HR], 1.38, 95 percent confidence interval [CI], 1.26–1.50). [AAIC 2022, abstract 62343]

This was driven by an increased risk of vascular dementia (HR, 1.58, 95 percent CI, 1.11–2.24) and other or unspecified dementias (HR, 1.51, 95 percent CI, 1.36–1.68) among women with vs without a history of preeclampsia or eclampsia. Conversely, preeclampsia or eclampsia was not associated with an increased risk of Alzheimer’s disease (HR, 1.04, 95 percent CI, 0.87–1.24).

The risk of vascular dementia was even further increased among women with vs without a history of gestational hypertension (HR, 2.75, 95 percent CI, 0.90–8.40). They also had increased risks of all-cause dementia (HR, 1.36, 95 percent CI, 1.03–1.79) and other or unspecified dementias (HR, 1.31, 95 percent CI, 0.96–1.80) than those without a history of gestational hypertension. There was no apparent association between a history of gestational hypertension and risk of Alzheimer’s disease.

Increased markers of vascular brain pathology after HDP

In a separate population-based prospective cohort study (Generation R study), researchers from the Erasmus MC University Medical Center, Rotterdam, Netherlands, followed 538 women* from early pregnancy. The 17.2 percent who had HDP during their index pregnancy were compared with the 82.7 percent who were normotensive. They were followed up at 15 years (median 14.6 years) post-pregnancy (mean age at follow up 46.5 years) where they underwent MRIs to examine brain tissue volume, white matter hyperintensities (WMH), lacunar infarcts, and cerebral microbleeds, all of which were markers of vascular brain pathology.

WMH volume was 38 percent higher among women with a history of HDP compared with women who were normotensive during pregnancy. [AAIC 2022, abstract 62354]

The increase in WMH volume was marked in women with a history of gestational hypertension, where it was 48 percent higher compared with that in women who were normotensive during pregnancy.

WMH volume was further increased among women who developed chronic hypertension following pregnancy, particularly in those who had a history of gestational hypertension. However, no differences were noted with regard to lacunar infarcts or cerebral microbleeds.

“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 study author Rowina Hussainali, a doctoral student in epidemiology and obstetrics and gynaecology at the Erasmus MC University Medical Center.

“Women with a history of HDP should be evaluated and treated early for hypertension and other cardiovascular risk factors,” she concluded.

“These data illuminate the importance of prenatal care and monitoring the long-term health of pregnant people,” remarked Dr Claire Sexton, senior director, Scientific Programs and Outreach, Alzheimer’s Association, who was not affiliated with the studies. “Considering the serious short- and long-term implications of HDP, early detection and treatment are vital to protect both the pregnant person and baby.”

“Those who experience any changes with their memory and cognition should have a discussion with their healthcare provider,” she cautioned.