Associations of hypertensive disorders of pregnancy with cognition, dementia, and brain structure: a Mendelian randomization study

Background: Observational studies have found associations between hypertensive disorders of pregnancy and an increased risk of cognitive dysfunction and reduced brain volume. However, the results of observational studies may have been influenced by confounding factors. This study applied two-sample Mendelian randomization (MR) to explore the causal associations of hypertensive disorders of pregnancy with cognition, dementia, and brain structure. Methods: Summary data on hypertensive disorders of pregnancy and their main subtypes, cognition, dementia, and brain structure were obtained from recent European genome-wide association studies. We computed the inverse-variance weighted, MR-Egger, and weighted median MR estimates. Cochran's Q statistics and the MR-Egger intercept test were used to quantify the heterogeneity and horizontal pleiotropy of the instrumental variables. Results: Genetically predicted preeclampsia or eclampsia was inversely associated with gray matter volume [beta = -0.072; 95% confidence interval (CI) = -0.131 to -0.014; P = 1.53 x 10(-2)]; possibly with brain volume (beta = -0.064; 95% CI = -0.117 to -0.012; P = 1.68 x 10(-2)). However, the association of hypertensive pregnancy disorders or gestational hypertension with brain structure was not significant. We did not find any significant association between hypertensive disorders of pregnancy, gestational hypertension, or preeclampsia or eclampsia and cognition and dementia-related outcomes. Conclusion: This study provided genetic evidence supporting an association between preeclampsia or eclampsia and reduced brain volume. This supports the view of PE as a risk factor for gray matter volume reduction.