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). 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. 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). 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.

中文翻译：

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中年血压与认知功能的关联：孟德尔随机研究。


高血压是否早在中年时期就对认知功能产生因果影响尚不清楚。我们使用孟德尔随机化 (MR) 方法研究了高血压 (BP) 是否会损害中年认知功能。我们采用双样本 MR 方法来研究血压与通过数字符号替换测试 (DSST)、雷伊听觉语言学习测试 (RAVLT) 和斯特鲁普干扰测试测量的中年认知表现之间的因果关系。我们使用 CARDIA 研究中总共 109 个已确定与 BP 相关的基因多态性作为工具变量，并估计了 1369 名中年成年人（平均年龄 (SD)：50.8 (3.3)，54.0% 女性）的基因-认知功能关联。基因预测的收缩压、舒张压或脉压每增加 10 mmHg，DSST 评分就会降低 4.9 至 7.7 分（P = 0.002，SBP；P = 0.005，DBP 和 P = 0.008，PP），而 10基因预测 SBP 的 mmHg 增量与 RAVLT 降低 0.7 点和 Stroop 升高 2.3 点相关（分别 P = 0.046 和 0.011）。该 MR 分析表明，高血压（尤其是 SBP）与中年期间处理速度、言语记忆和执行功能较差有因果关系。这些发现强调需要进一步研究血压失调对中年乃至整个生命周期认知健康的作用和机制。