Hypertensive Disorders of Pregnancy Linked With Late-Life Cognition

A history of hypertensive disorders of pregnancy (HDP) — gestational or chronic hypertension, or preeclampsia/eclampsia — was associated with a greater risk of cognitive decline later in life, longitudinal data showed.

Among 2,200 women in the Mayo Clinic Study of Aging, those with any HDP experienced greater declines in global cognition and attention/executive function compared with women who had all normotensive pregnancies, according to Michelle Mielke, PhD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues.

When stratified by HDP type, only women with preeclampsia/eclampsia had greater declines in z-scores of global cognition (b -0.039, P<0.001), language (b -0.032, P=0.001), and attention/executive function (b -0.040, P<0.001), Mielke and co-authors reported in Neurology.

Given that the association between HDP and cognitive decline was not attenuated by adjustments for vascular risk factors or conditions, “these results suggest that HDP, especially preeclampsia/eclampsia, is an independent risk factor for cognitive decline,” the researchers wrote.

“The results suggest an underlying vascular pathology and microvascular contribution, which is generally consistent with the literature,” they added.

The findings should prompt consideration of several important points, observed Calin Prodan, MD, of the University of Oklahoma in Oklahoma City, in accompanying editorial.

“First, we need to include a comprehensive and accurate pregnancy history when assessing cognitive impairment in women later in life,” Prodan pointed out.

“Second, it is essential to identify mechanisms responsible for these findings, and determine if these mechanisms differ depending on pregnancy history, vascular risk factor profile, treatment options, and adequate control of vascular risk factors,” he added.

HDP has been associated with subsequent comorbidities including an increased risk of hypertension 10 years later. About 15.3% of women have a HDP and 7.5% have preeclampsia during their lifetimes, Mielke and colleagues noted.

Studies of global and domain-specific cognitive decline and HDP have shown mixed results, with some suggesting women with a history of gestational hypertension or preeclampsia perform worse in midlife on measures of psychomotor speed, attention/executive function, or memory, the researchers said. “Other studies, however, have not found associations with psychomotor speed, attention/executive function, or memory,” they added.

The study included 2,239 women who enrolled in the Mayo Clinic Study of Aging between 2004 and 2019 and who underwent a cognitive battery of nine tests in four domains (memory, attention/executive function, language, and visuospatial) every 15 months over a median of about 5 years.

Median baseline age was 73; 82.8% of women had at least one pregnancy and 17.2% were nulliparous. At the baseline visit, the HDP and normotensive groups had comparable cognitive z-scores.

The researchers evaluated associations between pregnancy history (all normotensive, any HDP, HDP subtype, or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE status, smoking, hypertension, dyslipidemia, body mass index, diabetes, stroke, and heart disease.

Women with gestational or chronic hypertension did not differ in global or domain-specific cognitive decline compared with women with all normotensive pregnancies. Preeclampsia/eclampsia was not associated with memory or visuospatial decline.

Nulliparous women had lower global and domain-specific cognition (all P<0.05), after adjusting for age and education. Lower cognitive performance was most pronounced among nulliparous women with 12 or fewer years of education.

“Few studies have addressed nulliparity when examining the relationship between HDP and cognition, but our results highlight the importance of including all women in such analyses,” Mielke and co-authors noted.

The researchers acknowledged limitations of the study, including a lack of generalizability due to underrepresentation of diverse populations and of women with more severe HDP cases. In addition, the study had insufficient data to assess the impact of infertility, miscarriages, or multiple births, and whether or how hypertension was controlled.

“More research is needed to confirm our findings,” Mielke said in a statement. “However, these results suggest that managing and monitoring blood pressure during and after pregnancy is an important factor for brain health later in life.”