CVD Predictors of Cognitive Function Trajectory over 20 Years

描述(由申请人提供)：认知障碍和痴呆症阻碍健康衰老。一些证据表明，心血管疾病(CVD)及其危险因素(和相关生物标记物)会加速认知功能的下降，但大多数研究都是横断面的，或者有5年的随访。我们建议使用兰乔贝尔纳多研究(RBS)对老年社区居民进行的20年心血管疾病和认知功能测试(CFT)数据来检验基线和变化的心血管疾病危险因素与认知功能测试(CFT)表现的变化之间的关系。RBS成立于1972年，是一项血脂研究患病率研究，当时获得了心脏病、糖尿病、中风和高血压的病史，并测量了82%的成年居民的体重指数、空腹血糖、甘油三酯和胆固醇。从1984年开始，每四年有60%-87%的幸存社区参与者回到我们的研究诊所，那时我们会测量心血管疾病的危险因素，并更新生活方式、药物和病史。从1988年开始，大约相隔4年，在6次门诊中，每次完成3次或更多的标准CFT。到目前为止，1172名男性和女性至少在三个场合进行了重新测试，其中721人进行了四次或更多CFT检查。我们提出了一项关于心血管疾病危险因素(4个危险因素组和3个综合危险因素评分)以及临床和亚临床心血管疾病与成功认知老化之间关系的前瞻性研究。我们将成功的认知老化定义为在没有临床痴呆的情况下存活，并在CFTS(评估3个认知域的3个标准测试)上维持预定的表现。我们将首先确定有利的CVD危险因素是否与短期(4年)维持认知功能有关，然后进行长期(20年)轨迹研究，其中将包括危险因素的变化以及CFT的变化。我们将使用COX比例风险模型检验明确定义的成功认知老化的预测因素。将在教育、抑郁情绪、体重和体重变化、载脂蛋白E基因、药物和合并症的背景下研究相关性；机制将使用包括CRP、IL-6、IGF-1、类固醇激素和脂肪细胞因子在内的测量生物标记物进行研究。所有的分析都将基于特定的先验假设。我们的目标是将CVD风险因素和生物标记物的合理因果网络定义为暴露变量，更有利的属性预测认知功能较少或没有损失。纵向研究是解决多个观察到的联系的强度、独立性、暂时性和效果改变的最有力的方法。丰富的RBS数据集，以其长期重复的CVD和CFT测量而独一无二，将使我们能够确定CVD暴露变量如何影响认知功能的不同领域。考虑到人口老龄化，心血管疾病风险因素是可改变的，以及认知功能的维持是健康老龄化的重要组成部分，这一信息很重要。

DESCRIPTION (provided by applicant): Cognitive impairment and dementia preclude healthy aging. Several lines of evidence suggest that cardiovascular disease (CVD) and its risk factors (and related biomarkers) accelerate decline in cognitive function, but most studies are cross-sectional or have a < 5 year follow-up. We propose to use >20 years of CVD and cognitive function test (CFT) data from the Rancho Bernardo Study (RBS) of older community-dwelling adults to examine the association of baseline and changing CVD risk factors with change in CFT performance. The RBS was established as a Lipid Research Prevalence Study in 1972, when history of heart disease, diabetes, stroke, and hypertension was obtained, and body mass index, fasting plasma glucose, triglycerides and cholesterol were measured in 82% of adult residents. Beginning in 1984, 60-87% of surviving community-dwelling participants returned to our research clinic every four years, when CVD risk factors were measured, and lifestyle, medication, and medical history were updated. Beginning in 1988, 3 or more standard CFTs were completed at each of six clinic visits about 4 years apart. To date, 1172 men and women have been retested on at least three occasions, and 721 have had four or more CFT visits. We propose a prospective study of the association of CVD risk factors (4 risk factor groups and 3 composite risk factor scores) and clinical and subclinical CVD with successful cognitive aging. We define successful cognitive aging as survival without clinical dementia and maintenance of predefined performance on CFTs (3 standard tests assessing 3 cognitive domains). We will first establish whether favorable CVD risk factors are prospectively related to short term (4 year) maintained cognitive function, followed by longer term (20 year) trajectory studies which will include change in risk factors as well as change in CFTs. We will examine predictors of categorically-defined successful cognitive aging using Cox proportional hazard models. Associations will be examined in the context of education, depressed mood, weight and weight change, Apo E genotype, medications and comorbidities; mechanisms will be studied using measured biomarkers including CRP, IL-6, IGF-1, steroid hormones, and adipocytokines. All analyses will be based on specific a priori hypotheses. Our goal is to define a plausible web of causation for CVD risk factors and biomarkers as exposure variables, with more favorable attributes predicting less or no loss of cognitive function. Longitudinal studies are the strongest method for addressing the strength, independence, temporality, and effect modification of multiple observed associations. The rich RBS dataset, unique for its long-term repeated CVD & CFT measures, will allow us to determine how CVD exposure variables influence different domains of cognitive function. This information is important given the aging of the population, the fact that CVD risk factors are modifiable, and because the maintenance of cognitive function is an essential component of healthy aging.