Associations of Adverse Pregnancy Outcomes with Cognitive Impairment and Dementia: A Systematic Review and Meta-analysis
Mohammad Alirezaei1, Patrick Conley2, Katrin Wolfova3, Mitzi Gonzales2, Zaldy Tan2, Sarah Tom1, Lynn Yee4, Adam Brickman1, Natalie Bello2, Eliza Miller5
1Columbia University, 2Cedars-Sinai Medical Center, 3Charles University, 4Northwestern University, 5Columbia University Dept of Neurology
Objective:
We aimed to systematically review the literature examining the associations of Adverse Pregnancy outcomes (APOs) with mild cognitive impairment (MCI) and dementia in parous women.
Background:
APOs are associated with a higher risk of cerebrovascular disease in women, but it is less clear whether there is an independent association of APOs with MCI and dementia.
Design/Methods:
We searched PubMed, Web of Science, and EMBASE for papers published in any language between database inception and July 18, 2024. We included all studies reported MCI or dementia as outcomes and included women who experienced an APO, including hypertensive disorders of pregnancy, gestational diabetes, stillbirth, fetal growth restriction, preterm birth, or placental abruption, during a pregnancy lasting ≥ 20 weeks. We excluded studies focused on men, nulliparous women, women with pre-pregnancy conditions associated with abnormal cognition, or those examining cognitive impairment within six months of pregnancy. The study protocol was prospectively registered with PROSPERO (CRD42023453511).
Results:
Of the 11,251 references identified, 15 studies including 7,347,202 participants met inclusion criteria. Only one study reported MCI as an outcome, while 11 studies (6,263,431 participants) examining dementia had sufficient data for meta-analysis. A history of any APO was associated with higher risk of all-cause dementia (HR 1.32, 95% CI 1.17, 1.49, I²= 80.4%), Alzheimer’s disease (HR 1.26, 95% CI 1.04, 1.53, I²=62.8%), and vascular dementia (HR 1.94, 95% CI1.70, 2.21 , I²=0%). A history of any hypertensive disorder of pregnancy was significantly associated with all-cause dementia (HR 1.32, 95% CI 1.11, 1.57) and vascular dementia (HR 1.78, 95% CI 1.46, 2.17), but not Alzheimer’s disease (HR 1.24, 95% CI 0.98, 1.57).
Conclusions:
In the largest, most comprehensive meta-analysis to date, women with a history of any APOs had a significantly increased risk of future dementia with a moderately increased risk for Alzheimer’s disease and nearly double the risk of vascular dementia.
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