Renin-Angiotensin-Aldosterone System in Preeclampsia: Pathophysiological Insights and Links to Vascular Dementia

Preeclampsia, a condition characterized by new-onset hypertension during pregnancy and ≥1 indices of organ damage, is a major driver of both short- and long-term maternal health outcomes. Individuals with a history of preeclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked preeclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither the mechanisms underlying the causes of preeclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia are a type of dementia caused by reduced cerebral blood flow, often resulting from vascular dysfunction associated with small vessel damage or chronic hypertension. The renin-angiotensin-aldosterone system (RAAS) is a hormone system with a major role in regulating blood pressure, fluid homeostasis, and vascular function inside and outside of pregnancy. The RAAS is markedly activated during pregnancy; preeclampsia is associated with disruptions in the normal activity of the RAAS, including excessive Ang (angiotensin) II type 1 receptor signaling, and loss of protective effects of Ang-(1-7) and Ang II type 2 receptors. Preexisting hypertension may impair the normal RAAS response to pregnancy, increasing susceptibility to vascular damage both during and after pregnancy. Results from human and animal studies indicate that dysregulation of the RAAS is a shared pathway underlying vascular dysfunction in both preeclampsia and vascular contributions to cognitive impairment and dementia, suggesting a mechanistic link between these 2 conditions. Persistent endothelial damage, impaired vascular remodeling, and chronic activation of Ang II type 1 and mineralocorticoid receptor signaling may increase long-term risk. This connection underscores the importance of monitoring and managing blood pressure during pregnancy and in women with a history of preeclampsia to mitigate the risk of dementia.