Severe Preeclampsia During Pregnancy Linked With Late-Life Cognitive Issues, Inflammation
Inflammatory coagulation pathway activator positive extracellular vesicles were significantly increased in women with a history of severe preeclampsia compared with controls and those with milder cases.
Vesna Garovic, MD, PhD
According to data presented at the 2022 Alzheimer’s Association International Conference (AAIC), July 31 to August 4, in San Diego, California, severe cases of preeclampsia (PE), a pregnancy specific hypertensive disorder, were found to elevate markers of neuroinflammation and neurovascular damage, while demonstrating increased amyloid-ß concentration.1
The study included 40 women with histories of normotensive pregnancies, considered the control group, with 40 age- and parity-matched women with history of mild (n = 33) or severe (n = 7) PE. When comparing the groups, those with history of severe PE had a significantly higher concentration of amyloid-ß carrying extracellular vesicles (EVs; P = .003). Additionally, plasma concentration of total amyloid-ß was also significantly greater in women with history of severe vs mild PE (P = .037).
"It’s important because if we say that after delivery, preeclampsia is cured, then we ignore symptoms and signs that these women may develop immediately after delivery that require attention of medical specialties, sometimes even neurology specialists,” senior investigator Vesna Garovic, MD, PhD, nephrologist, Mayo Clinic, told NeurologyLive®. "We’re lucky it’s not fatal, but it’s not uncommon for a woman to develop postpartum preeclampsia, which presents itself with eclampsia—ie, seizures. The concept that delivery is a cure is wrong, both when it comes to the immediate care of these patients, but also treating the long-term consequences of the disease."
Blood-borne EVs derived from neurovascular cellular activation were determined using standardized digital flow cytometry, while plasma concentration of amyloid-ß was measured using ELISA. Differences among the groups were tested by ANOVA, with the least difference test for post-hoc analysis. Pearson correlation coefficient was used to assess the association between EVs and MRI brain imaging.
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In addition to having a higher concentration of amyloid-ß, women with a history of severe PE had significantly greater EVs positive for the markers of blood-brain barrier-endothelial damage (P = .008) and inflammatory coagulation pathway activator (P = .002) compared with controls, as well as compared with those with a history of mild PE. Additionally, the number of tissue factor positive EVs was negatively correlated with total gray matter volume (P <.05).
When asked whether the data would play a role in future clinical trials, Vesna replied "absolutely," adding, "There are several big cohorts that follow these women longitudinally. The major question is whether this change occurs immediately after preeclampsia—whether this is during mid-age or during the postmenopausal period—as well as the interaction between other reproductive recognized risks and preeclampsia."
Previously, Garovic and colleagues investigated the combined effect of both preeclampsia and late-life hypertension using the same cohort. The study included women with a history of normotensive pregnancy who have late-life hypertension (n = 8; median age, 62 years), women with a history of normotensive pregnancy who do not have late-life hypertension (n = 32; median age, 59 years), women with a history of preeclampsia who have late-life hypertension (n = 24; median age, 60 years), and women with a history of preeclampsia who do not have late-life hypertension (n = 16; median age, 57 years).2
All told, the results indicated that total gray matters were smaller in women with a history of preeclampsia and late-life hypertension compared with the other groups. Additionally, using voxel-based morphometry, findings showed that the volume changes were localized to the posterior brain regions, particularly the occipital lobe gray matter in women with a history of preeclampsia with or without late-life hypertension.
"Despite the increasing body of evidence that preeclampsia has long-term effects, not only cardiovascular risks, but now as we learn about cognition, it’s very important to educate primary care providers about the risks associated with preeclampsia, and also educate the patients to bring that history to the physicians who are taking care of them," Garovic added. "Because we may not understand what exactly is happening at the molecular level, but there are some coexisting risk factors that can be effectively treated, such as hypertension, diabetes, and maybe introduce lifestyle modifications with respect to optimal body weight, or exercise regimen."
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