Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life

Background and Objectives Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later-life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later-life.

Methods Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical-record abstracted pregnancy information. A cognitive battery of nine tests was conducted every 15 months. Global cognitive and domain-specific z-scores (memory, executive/attention, visuospatial, language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined.

Results Of the 2,239 women, 1,854 (82.8%) had at least one pregnancy (1,607 all normotensive, 100 GH/CH, 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E versus women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p<0.05) in age- and education-adjusted models. There was an interaction (p=0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p<0.001) versus 12+ years (b = -0.11, p=0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z-scores compared to women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p<0.001), language (beta = -0.03, p=0.001), and attention (beta = -0.04, p<0.001) z-scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results.

Discussion Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.