Key result
A 10 mmHg increment in genetically-predicted systolic blood pressure was causally associated with a 4.9-point lower Digit Symbol Substitution Test score at midlife.
Why the study?
Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear.
Does genetically-predicted high blood pressure reduce cognitive function in middle-aged adults?
Observational (n=1,369)
Yes
Does genetically-predicted high blood pressure reduce cognitive function in middle-aged adults?
Effect estimate: -0.49 points per 1 mmHg SBP (95% CI -0.79 to -0.18)
p-value: p=0.002
Genetically predicted higher blood pressure, particularly systolic blood pressure, is causally associated with poorer processing speed, verbal memory, and executive function during midlife.
Genetically predicted higher SBP may impair midlife processing speed; hypothesis-generating, needs prospective confirmation before practice change.
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.
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Sun et al. (2020) conducted an observational in Healthy middle-aged adults (n=1,369). Genetically-predicted blood pressure was evaluated on Digit Symbol Substitution Test (DSST) score (-0.49 points per 1 mmHg SBP, 95% CI -0.79 to -0.18, p=0.002). A 10 mmHg increment in genetically-predicted systolic blood pressure was causally associated with a 4.9-point lower Digit Symbol Substitution Test score at midlife.
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