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Related Experiment Video

Updated: Feb 13, 2026

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
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Causal effects of reproductive traits on cognitive function: A two-sample and multivariable mendelian randomization

Xia Wang1, Yunyun Guo2

  • 1The Department of Obstetrics at the Affiliated Hospital of Southwest Medical University, Luzhou, China.

International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics
|February 12, 2026
PubMed
Summary

Earlier age at first sexual intercourse and first birth are linked to cognitive decline. These reproductive traits significantly impact cognitive function, highlighting their role in brain health.

Keywords:
causal inferencecognitionmendelian randomizationreproductive traits

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Area of Science:

  • Reproductive Health
  • Neuroscience
  • Genetics

Background:

  • Associations between reproductive traits and cognitive function are inconsistent and causality remains unclear.
  • Mendelian randomization (MR) offers a method to investigate potential causal relationships.

Purpose of the Study:

  • To assess the causal impact of reproductive traits on cognitive function using MR analysis.
  • To determine if these associations are independent of body mass index (BMI) and educational attainment (EA).

Main Methods:

  • Two-sample univariable MR (UVMR) and multivariable MR (MVMR) were employed.
  • Inverse variance weighted (IVW) method was used for primary analyses, with sensitivity analyses for robustness.
  • MVMR assessed independence from BMI and EA.

Main Results:

  • Younger age at first sexual intercourse (AFS) and earlier age at first birth (AFB) were significantly associated with poorer cognitive function.
  • Earlier AFB correlated with lower cognitive performance, fluid intelligence, and memory.
  • Hormone replacement therapy (HRT) showed a potential association with cognitive decline, but evidence was insufficient after adjustments.

Conclusions:

  • Earlier AFS and AFB are identified as risk factors for cognitive decline.
  • The influence of oral contraceptive pills and fewer live births on cognition is partly mediated by EA.
  • Reproductive traits play a significant role in modulating cognitive function.