Impaired Cognition and Brain Atrophy Decades After Hypertensive Pregnancy Disorders

Abstract

Background Hypertensive pregnancy disorders have been associated with subjective cognitive complaints or brain white matter lesions five to ten years after the hypertensive pregnancy. The long-term effects of hypertensive pregnancies on brain structure and cognitive function remain unknown. Methods and Results This study included 1279 women who participated in the Family Blood Pressure Project Genetic Epidemiology Network of Arteriopathy (GENOA) study. As part of the ancillary Genetics of Microangiopathic Brain Injury study, a neurocognitive battery was administered; 1075 also had a brain MRI. A history of a hypertensive pregnancy disorder was obtained by self-report using a validated questionnaire. Linear models fit with generalized estimating equations were used to assess the association between hypertensive pregnancy disorders and cognition, adjusting for age, race, education, body mass index, smoking, current hypertension, hypertension duration, and family history of hypertension. Regression models for the brain MRI outcomes also were adjusted for total intracranial volume. Women with histories of hypertensive pregnancy disorders performed worse on all measures of processing speed: Digital Symbol Substitution Test (mean score 41.2 vs 43.4, P=0.005), Trail Making Test Part A (mean seconds 45.1 vs 42.2, P=0.035), and Stroop (mean score 173.9 vs 181.0, P=0.002) and had smaller brain volumes compared to women with histories of normotensive pregnancies (286 vs 297, P=0.023). Conclusions Hypertensive pregnancy disorders are associated with worse performance on tests of processing speed and smaller brain volumes decades later. Population-based studies are needed to provide critical insight as to the contribution of hypertensive pregnancies to risk of cognitive decline and dementia.

Preeclampsia and the brain: neural control of cardiovascular changes during pregnancy and neurological outcomes of preeclampsia

“…Women in the PE group had significantly smaller brain volumes, with corresponding increases in lateral ventricular volumes. A recent study involving a large multiethnic and racially diverse sample observed that women with a history of hypertensive pregnancy had smaller brain volumes and larger degrees of atrophy decades after the index pregnancy (229). While not a sole indicator of neurological dysfunction, these alterations in brain size and volume are accompanied by changes in cerebral hemodynamics, electrophysiology, cognition, and behavior in human PE patients.…”

“…Diagnostic imaging reveals that these WMLs can persist for years after the index pregnancy (22–24, 229). Counterintuitively, the pattern of distribution of WMLs associated with preeclampsia differs from that of Posterior Reversible Encephalopathy Syndrome (PRES).…”

“…However, a long-term follow up study found no evidence of neurocognitive dysfunction despite the self-reporting of impairments, but the investigators did conclude that this increase in self-reported deficits is an indicator for cognitive impairment and/or dementia later in life (28). A more recent study concluded that hypertensive pregnancy disorders may be independent risk factors of cognitive decline, after adjusting for cardiovascular disease and known cardiovascular disease risk factors (229). Human subjects with a mean age of ~61 years, from a large multiracial sample, demonstrated significant deficits in processing speed decades after the index pregnancy, even when the results were adjusted for abnormal estimated glomerular filtration rate (eGFR) (229).…”

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

“…Studies have suggested that hypertensive pregnancy disorders have an increased, sex-specific risk of cognitive decline and dementia among women 5 to 10 years after the hypertensive pregnancy (Aukes et al 2007;Postma et al 2014a;. Moreover, a recent study has shown that hypertensive pregnancy disorders are associated with worse performance in tests of processing speed and smaller brain volumes decades later, when compared with women with histories of normotensive pregnancies (Mielke et al 2016). Other studies have demonstrated that stress during pregnancy durably hampers maternal body-weight growth, increases anxiety-like behaviors, and affects reactivity to stress in mothers more than 1 month after the stress exposure (Darnaudéry et al 2004).…”

“…These data imply a long-term, significant impact of adverse pregnancy on behaviors in mothers. Given normal reproduction experience and the adverse gestational conditions mentioned above can chronically affect cognitive functioning or other behaviors (Li et al 2013;Mielke et al 2016;Darnaudéry et al 2004), so it is plausible to hypothesize that gestational inflammation can impact the AAMI and corresponding neural substrates in the mother-self during aging.…”