Bown Corey W, Liu Dandan, Osborn Katie E, Gupta Deepak K, Mendes Lisa A, Pechman Kimberly R, Hohman Timothy J, Wang Thomas J, Gifford Katherine A, Jefferson Angela L
Department of Neurology Vanderbilt Memory & Alzheimer's Center Vanderbilt University Medical Center Nashville TN.
Department of Biostatistics Vanderbilt University Medical Center Nashville TN.
J Am Heart Assoc. 2019 Aug 6;8(15):e011146. doi: 10.1161/JAHA.118.011146. Epub 2019 Jul 31.
Background Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-ε4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-ε4 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73±7 years, 42% female) underwent echocardiography to determine cardiac output (L/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and ε4 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-ε4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output×APOE-ε4 status interaction and again stratified by ε4 carrier status. Cardiac output×APOE-ε4 status related to naming (β=0.91, P=0.0009), category fluency (β=1.2, P=0.01), information processing speed (β=-5.4, P=0.001), visuospatial skill (β=0.85, P=0.003), and executive function performances (β=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-ε4 carriers. Conclusions APOE-ε4 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the ε4 allele. These findings add to increasing evidence that APOE-ε4 carrier status has important implications for associations between vascular and brain health in aging adults.
背景 心输出量的细微减少与脑血流量降低有关，尤其是在阿尔茨海默病病理最初发展的区域。载脂蛋白E（APOE）-ε4是阿尔茨海默病的一种遗传易感性风险因素，它也会影响血管损伤。本研究调查了APOE-ε4携带者状态是否会改变心输出量与认知之间的横断面关联。方法与结果 范德比尔特记忆与衰老项目中无临床中风和痴呆的参与者（n = 306，73±7岁，42%为女性）接受了超声心动图检查以确定心输出量（升/分钟）、全面的神经心理学评估，并抽取静脉血以确定APOE基因型和ε4携带者状态。线性回归将心输出量与神经心理学测试表现相关联，对年龄、性别、教育程度、种族/族裔、体表面积、认知诊断、弗雷明汉姆中风风险概况和APOE-ε4状态进行了调整。主效应模型无统计学意义（P>0.19）。在相同的协变量下，重复模型测试心输出量×APOE-ε4状态的交互作用，并再次按ε4携带者状态进行分层。心输出量×APOE-ε4状态与命名（β = 0.91，P = 0.0009）、类别流畅性（β = 1.2，P = 0.01）、信息处理速度（β = -5.4，P = 0.001）、视觉空间技能（β = 0.85，P = 0.003）和执行功能表现（β = 0.22，P = 0.002）相关。分层模型表明，较低的心输出量与APOE-ε4携带者中较差的神经心理学表现相关。结论 APOE-ε4携带者状态似乎会改变心输出量与神经心理学表现之间的横断面关联，使得较低的心输出量与ε4等位基因携带者中较差的表现相关。这些发现进一步证明了APOE-ε4携带者状态对老年成年人血管与大脑健康之间的关联具有重要意义。
