Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, TX, 77030, USA.
Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
BMC Med Genomics. 2020 Aug 26;13(1):121. doi: 10.1186/s12920-020-00769-y.
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.
高血压是否早在中年就对认知功能有因果影响尚不清楚。我们通过孟德尔随机化（MR）研究，调查了高血压（BP）是否会对中年认知功能产生因果影响。
我们采用两样本 MR 方法，研究了 BP 与数字符号替代测试（DSST）、 Rey 听觉言语学习测试（RAVLT）和 Stroop 干扰测试中测量的中年认知表现之间的因果关系。我们共使用了 109 个与 BP 具有明确关联的遗传多态性作为工具变量，并在来自 CARDIA 研究的 1369 名中年成年人（平均年龄（SD）：50.8（3.3），54.0%为女性）中估计了基因-认知功能的关联。
遗传预测的收缩压、舒张压或脉压每增加 10mmHg，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），而遗传预测的 SBP 每增加 10mmHg，RAVLT 就会降低 0.7 分，Stroop 就会升高 2.3 分（P=0.046 和 0.011，分别）。
这项 MR 分析表明，高血压，尤其是 SBP，与中年时的处理速度、言语记忆和执行功能较差有因果关系。这些发现强调了需要进一步研究 BP 失调对中年认知健康的作用和机制，也许更广泛地说，贯穿整个生命周期。
