Departments of Neurology (S.M., S.K., C.R.G., A.J.N., F.A.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.
Preventive Medicine (S.S., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago, IL.
Circulation. 2020 Mar 3;141(9):712-724. doi: 10.1161/CIRCULATIONAHA.119.042502. Epub 2019 Nov 21.
High blood pressure (BP) is a known risk factor for mobility and cognitive impairment in older adults. This study tested the association of cumulative BP exposure from young adulthood to midlife with gait and cognitive function in midlife. Furthermore, we tested whether these associations were modified by cerebral white matter hyperintensity (WMH) burden.
We included 191 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults), a community-based cohort of young individuals followed over 30 years. Cumulative BP was calculated as the area under the curve (mm Hg×years) from baseline up to year 30 examination. Gait and cognition were assessed at the year 30 examination. Cerebral WMH was available at year 30 in a subset of participants (n=144) who underwent magnetic resonance imaging. Multiple linear regression models were used to assess the association of cumulative BP exposure with gait and cognition. To test effect modification by WMH burden, participants were stratified at the median of WMH and tested for interaction.
Higher cumulative systolic and diastolic BPs were associated with slower walking speed (both =0.010), smaller step length (=0.011 and 0.005, respectively), and higher gait variability (=0.018 and 0.001, respectively). Higher cumulative systolic BP was associated with lower cognitive performance in the executive (=0.021), memory (=0.015), and global domains (=0.010), and higher cumulative diastolic BP was associated with lower cognitive performance in the memory domain (=0.012). All associations were independent of socio-demographics and vascular risk factors (body mass index, smoking, diabetes mellitus and total cholesterol). The association between cumulative BP and gait was moderated by WMH burden (interaction <0.05). However, the relation between cumulative BP and cognitive function was not different based on the WMH burden (interaction >0.05).
Exposure to higher BP levels from young to midlife is associated with worse gait and cognitive performance in midlife. Furthermore, WMH moderates the association of cumulative BP exposure with gait, but not with cognitive function in midlife. The mechanisms underpinning the impact of BP exposure on brain structure and function must be investigated in longitudinal studies using a life course approach.
高血压（BP）是老年人行动和认知障碍的已知危险因素。本研究测试了从青年到中年的累积 BP 暴露与中年步态和认知功能的关系。此外，我们还测试了这些关联是否受到脑白质高信号（WMH）负担的影响。
我们纳入了来自 CARDIA 研究（年轻人冠状动脉风险发展研究）的 191 名参与者，这是一项基于社区的年轻人队列，随访时间超过 30 年。累积 BP 计算为从基线到 30 年检查的曲线下面积（mmHg×年）。步态和认知在 30 年检查时进行评估。在接受磁共振成像检查的一部分参与者（n=144）中，30 年时可获得脑 WMH 数据。使用多元线性回归模型评估累积 BP 暴露与步态和认知的关系。为了测试 WMH 负担的效应修饰，根据 WMH 的中位数对参与者进行分层，并测试交互作用。
较高的累积收缩压和舒张压与较慢的步行速度（均为 0.010）、较小的步长（分别为 0.011 和 0.005）和更高的步态变异性（分别为 0.018 和 0.001）相关。较高的累积收缩压与执行功能（=0.021）、记忆功能（=0.015）和整体功能（=0.010）认知表现降低相关，较高的累积舒张压与记忆域认知表现降低相关（=0.012）。所有关联均独立于社会人口统计学和血管危险因素（体重指数、吸烟、糖尿病和总胆固醇）。累积 BP 与步态的关系受 WMH 负担的调节（交互作用<0.05）。然而，基于 WMH 负担，累积 BP 与认知功能之间的关系没有差异（交互作用>0.05）。
从青年到中年的较高 BP 水平暴露与中年时的步态和认知功能较差有关。此外，WMH 调节了累积 BP 暴露与步态的关系，但不调节中年时的认知功能。必须使用基于生命历程的纵向研究来研究 BP 暴露对大脑结构和功能的影响的潜在机制。
