Association of blood pressure with cognitive function at midlife: a Mendelian randomization study

BMC Med Genomics. 2020 Aug 26;13(1):121. doi: 10.1186/s12920-020-00769-y.


Background: Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear. We investigated whether high blood pressure (BP) causally impairs cognitive function at midlife using Mendelian Randomization (MR).

Methods: We applied a two-sample MR approach to investigate the causal relationship between BP and midlife cognitive performance measured by the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and Stroop Interference test. We used a total of 109 genetic polymorphisms with established associations with BP as instrumental variables and estimated gene-cognitive function association in 1369 middle-aged adults (Mean age (SD): 50.8 (3.3), 54.0% women) from the CARDIA study.

Results: A 10 mmHg increment in genetically-predicted systolic, diastolic, or pulse pressure was associated with a 4.9 to 7.7-point lower DSST score (P = 0.002, SBP; P = 0.005, DBP and P = 0.008, PP), while a 10 mmHg increment in genetically-predicted SBP was associated with a 0.7 point lower RAVLT and a 2.3 point higher Stroop (P = 0.046 and 0.011, respectively).

Conclusions: This MR analysis shows that high BP, especially SBP, is causally associated with poorer processing speed, verbal memory, and executive function during midlife. These findings emphasize the need for further investigation of the role and mechanisms of BP dysregulation on cognitive health in middle age and perhaps, more broadly, across the lifespan.

Keywords: Blood pressure; Cognitive disorders; Dementia; Mendelian randomization; Risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology*
  • Female
  • Genetic Markers*
  • Genetic Variation*
  • Humans
  • Hypertension / complications*
  • Machine Learning
  • Male
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Risk Factors


  • Genetic Markers