Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis

Abstract

BACKGROUND: Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP’s vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes. METHODS: Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer’s disease, vascular dementia, or other/unspecified dementias. RESULTS: For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18–1.61]; P <0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32–4.24]; P <0.01). CONCLUSIONS: Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP’s effect on all-cause dementia, and specifically vascular dementia, is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: CRD42020185630

Hypertensive disorders of pregnancy

“…By contrast, gestational hypertension is associated with a 3.6-fold increase in risk of end stage kidney disease and a 1.5-fold increase in risk of chronic kidney disease 138. Overall, HDP are associated with a 1.4-fold increase in risk of dementia,140 with pre-eclampsia being associated with a 2.6-fold increase in risk of vascular dementia 141. Pre-eclampsia has been associated with a 1.5-fold and 1.8-fold increase in risk of venous thromboembolism and premature mortality, respectively 122.…”

Translation of mechanistic advances in preeclampsia to the clinic: Long and winding road

“…191 Furthermore, there appears to be a dose effect, with women who experience recurrent preeclampsia facing an even greater risk. 194,213,214 Epidemiological studies have also shown an increased risk of end-stage renal disease, 208,212,215,216 metabolic syndrome, 212 diabetes, 217,218 cognitive dysfunction, [219][220][221] stroke and other neurological complications. 208,221,222 Although sFlt-1 levels fall after delivery, when examined at two years post-partum, we demonstrated that women with a history of preeclampsia had altered angiogenic profiles and insulin resistance compared to women without a history of preeclampsia.…”

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

“…Observational evidence suggests that women with a history of HDP, especially PE, are at greater risk of developing cognitive dysfunction later in life [11]. In addition, a recent meta-analysis revealed a 38% higher risk of all-cause dementia (ACD) in women with HDP than in those without HDP, and patients with HDP had over a 3-fold higher risk of vascular dementia (VaD) [12]. Moreover, a recent clinical study in the United States reported a significantly increased risk of death due to Alzheimer's disease (AD) in women with a history of PE [13].…”