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

Daokun Sun,Lenore J Launer,Kristine Yaffe,Emy A Thomas,Stephen Sidney,Myriam Fornage

doi:10.1186/s12920-020-00769-y

Abstract

BackgroundWhether 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).MethodsWe 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.ResultsA 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).ConclusionsThis 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.

Highlights

Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear
Several studies have reported that high blood pressure (BP) developed by middle age is associated with cognitive decline [2, 3] and with global and domain-specific cognitive impairment
The more recent SPRINT MIND trial reported that, in older adults at increased risk of cardiovascular disease, intensive systolic BP control reduced the risk of mild cognitive impairment (MCI) as well as the combined occurrence of MCI or dementia [9]

Summary

Introduction

Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear. Several studies have reported that high blood pressure (BP) developed by middle age is associated with cognitive decline [2, 3] and with global and domain-specific cognitive impairment. The more recent SPRINT MIND trial reported that, in older adults at increased risk of cardiovascular disease, intensive systolic BP control reduced the risk of mild cognitive impairment (MCI) as well as the combined occurrence of MCI or dementia [9]. We employed a two-sample MR approach to expand existing knowledge about the effect of high BP burden on cognitive health during middle age [10], a pivotal period in the life course when cognitive function begins to decline among healthy adults [11]

Methods

Results

Conclusion