Faculty of Medicine (M.J.L., A.T., B.C.P.L., J.D.C., P.S.S.), University of New South Wales, Sydney, Australia.
Centre for Healthy Brain Aging, Discipline of Psychiatry and Mental Health (M.J.L., A.T., B.C.P.L., J.D.C., P.S.S.), University of New South Wales, Sydney, Australia.
Hypertension. 2023 Oct;80(10):2112-2121. doi: 10.1161/HYPERTENSIONAHA.123.21612. Epub 2023 Aug 17.
This UK Biobank study uses a mendelian randomization approach to mitigate the variability and confounding that has affected previous analyses of the relationship between measured blood pressure (BP) and cognition and thus delineate the true association between the two.
Systolic BP (SBP) and diastolic BP polygenic risk scores (PRSs) were calculated using summary statistics from the International Consortium of Blood Pressure-Genome Wide Association Study (n=299 024). Adjusted nonlinear mixed-effects regression models were used, including a natural splines term for BP-PRS with outcomes of fluid intelligence, reaction time (RT), and composite attention score. Moderating effects of age, sex, and antihypertensive use were assessed in separate models.
There were 448 575 participants (mean age, 56.3 years; age range, 37-72 years) included in the analysis after genetic and neurological disease exclusions. Genetic propensity for high SBP had an approximately linear association with worsened fluid intelligence (=0.0018). This relationship was significantly moderated by age (<0.0001). By contrast, genetic propensity for high and low SBP and diastolic BP predicted worse attention function (=0.0099 and =0.0019), with high PRSs predicting worse function than low PRSs. Genetic propensity for low SBP and diastolic BP was associated with considerably worse RTs, while for high SBP-PRSs, the RT plateaued (<0.0001). The relationships between RT and the PRSs were significantly moderated by sex (<0.0001) and antihypertensive use (<0.0001).
Genetic propensity for high and low BP impacts on midlife cognition in subtle ways and differentially affects cognitive domains. While a genetic propensity to low BP may preserve nontimed tests in midlife, it may come at a trade-off with worsened attention scores and RT.
本项英国生物库研究采用孟德尔随机化方法，减轻了先前分析血压与认知之间关系的研究中存在的变异性和混杂因素的影响，从而阐明了两者之间的真实关联。
使用国际血压-全基因组关联研究联盟汇总统计数据计算收缩压（SBP）和舒张压多基因风险评分（PRS）（n=299024）。采用调整后的非线性混合效应回归模型，包括 SBP-PRS 结果（流体智力、反应时间（RT）和综合注意力评分）的自然样条项。在单独的模型中评估年龄、性别和降压药物使用的调节作用。
在进行遗传和神经疾病排除后，有 448575 名参与者（平均年龄 56.3 岁；年龄范围 37-72 岁）纳入分析。SBP 高的遗传倾向与流体智力下降呈近似线性关联（=0.0018）。这种关系受到年龄的显著调节（<0.0001）。相比之下，SBP 和舒张压高和低的遗传倾向预测注意力功能下降（=0.0099 和 =0.0019），高 PRS 预测功能下降比低 PRS 更明显。SBP 和舒张压低的遗传倾向与 RT 明显延长有关，而 SBP-PRS 高的 RT 趋于平稳（<0.0001）。RT 与 PRS 之间的关系受到性别（<0.0001）和降压药物使用（<0.0001）的显著调节。
BP 高和低的遗传倾向以微妙的方式影响中年认知，并对认知领域产生不同影响。虽然低 BP 的遗传倾向可能在中年时保持非定时测试，但可能会以注意力评分和 RT 下降为代价。
