Association of preeclampsia with long-term risk of neurodegenerative disorders

Preeclampsia (PE) is a common complication of pregnancy linked to increased lifetime risk of multiple comorbidities. However, the link between PE and development of adverse neurologic conditions is still poorly understood. Our objective was to investigate the risk of neurodegenerative disorders for women with PE compared to those without PE.

We utilized the TriNetX database including electronic health records from 66 healthcare organizations and identified women 18+ years old with their last delivery between January 2000 and December 2023. PE was defined using ICD-10 codes that occurred before delivery up until December 2020. The comparator group included pregnant women in the same period without PE diagnosis. After 1:1 propensity score matching on age at index pregnancy, demographics, health utilization, comorbidities, depression, reproductive factors, and body mass index, hazard ratios (HR), and 95% confidence intervals (CIs) for cognitive disorders were estimated between the PE and comparator group using a Cox proportional hazard regression model. Cognitive outcomes were identified by ICD-10 codes and censored until one of the following conditions was met: (1) development of an outcome, (2) July 26, 2024, or (3) loss to follow-up in the system.

The PE group had a 9% increased risk of symptomatic cognitive impairment (HR 1.09; 95% CI 1.03, 1.16) and a 9% increased risk of composite cognitive impairment outcomes, including clinical, symptomatic, mild cognitive impairment, dementia, or related medication use (HR 1.09; 95% CI 1.03, 1.15) compared to the non-PE group. Similar trends were observed in the term birth subgroup for symptomatic cognitive impairment (HR 1.06; 95% CI 1.00, 1.12) and composite outcomes(HR 1.06; 95% CI 1.01, 1.13). No significant associations were found in the preterm subgroup due to limited events. Risk of Parkinson's disease, parkinsonism, or related outcomes was not statistically different in the main model but was higher in sensitivity analyses with natural language processing (NLP) and accounting for death as competing risk. Cognitive impairment, dementia/Alzheimer's, and vascular dementia showed no differences in the main or NLP sensitivity analyses but were elevated in the competing risk sensitivity analysis.

Our findings demonstrate an increased risk of cognitive impairment among individuals with a history of PE, with additional associations for Parkinson's disease and parkinsonism identified in sensitivity analyses. These results highlight the importance of obstetrical health as a predictor of lifelong neurocognitive health, underscoring the need for targeted surveillance and early intervention strategies for neurodegenerative diseases in this population.