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Hypertensive Disorders of Pregnancy Associated With Worse Cognition

Women with HDP were found to perform worse on cognitive tests 15 years after delivery than their counterparts.

A recent study investigated women that experienced hypertensive disorders of pregnancy (HDP) 15 years after pregnancy and found that a history of HDP is independently associated with poorer working memory and verbal memory.

Women with HDP had a lower global cognition factor (g-factor) than women with a previous normotensive pregnancy (mean difference, –0.22; 90% range, –2.06 to 1.29). HDP was also negatively associated with immediate recall (–0.25; 95% CI, –0.44 to –0.06) and delayed recall (–0.30; 95% CI, –0.50 to –0.10) on the 15-word learning test (15WLT).

Study author M. Arfan Ikram, MD, PhD, adjunct professor of epidemiology, Harvard T.H. Chan School of Public Health, and professor and head of neuro-epidemiologic research, department of epidemiology, Erasmus University Medical Center Rotterdam, and colleagues wrote that “recent studies show a possible association of pre-eclampsia with cognitive impairment and even dementia, leading some to question whether cognitive impairment or dementia should be included as a potentially preventable outcome in cardiovascular disease guidelines, rather than exclusively focusing on cardiovascular disease risk reduction in women with previous HDP.”

Ikram and colleagues performed this sub-study, termed ORACLE (MEC 2015-749 NL55105.078.15), of the Generation R study, an ongoing population-based prospective birth cohort study. They analyzed data from 596 women from Rotterdam with delivery dates between April 2002 and January 2006. 

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The women were an average age of 46.4 years (standard deviation [SD], 4.3) at the time of cognitive testing. The median time between pregnancy and testing was 14.7 years (90% range, 13.9–16.1). Of these women, 481 (80.7%) had a previous normotensive pregnancy, and 115 (18.0%) had HDP. Of the women with HDP, 80 (69.6%) had gestational hypertension (GH) and 35 (30.4%) had pre-eclampsia. Almost all women with pre-eclampsia (n = 33; 94.3%) developed it at term, as defined as an onset after 34 weeks of gestation. Prior to cognitive testing, 68 (11.4%) women were classified as hypertensive.

Ikram and colleagues assessed cognitive performance by measuring executive function, processing speed, verbal memory, motor function, and visuospatial ability. A g-factor was derived from these measurements.

Women with HDP performed worse on various facets of the 15WLT. The median score on the immediate recall subtask was 25.0 (90% range, 14.7–35.0) in women with HDP as compared to 28.0 by women without HDP (90% range, 17.0–36.0; P <.001). The median score on the delayed recall subtask was 8.0 (90% range, 3.0–13.0) in women with HDP as compared to 9.0 (90% range, 4.0–13.0; P <.001) in women without HDP. Women with HDP also had a worse median score on the Stroop color naming task (22.0; 90% range, 17.0–32.0) than women without HDP (21.0; 90% range, 16.0–29.0); a worse median score on the letter digit substitution task (36.0; 90% range, 26.5–46.0) than women without HDP (38.0; 90% range, 28.0–48.0; P = .01); and a worse median score on the design organization test (34.0; 90% range, 17.0–49.0) than women without HDP (38.0; 90% range, 22.0–55.1; P =.03).

Ikram et al performed sensitivity analyses that showed all associations remained significant after adjusting for cofounders. They also performed a sensitivity analysis excluding pre-eclampsia and found that all associations remained; the association between HDP and memory was mainly driven by GH.

“Not only women with a history of pre-eclampsia, but also GH should be monitored closely after their pregnancy. Whether early treatment of hypertension prevents cognitive decline in women with a history of HDP should be investigated in clinical trials. Both clinicians and women with a history of HDP should be aware of these patients' risk of cognitive impairment later in life,” Ikram and colleagues concluded.

Adank MC, Hussainali RF, Oosterveer LC, et al. Hypertensive disorders of pregnancy and cognitive impairment: A prospective cohort study. Neurology. Published online December 30, 2020. doi: 10.1212/WNL.0000000000011363