Lifecourse CVD Risk and Midlife Cognitive Trajectories and Brain Aging: Implications for Alzheimer's and Dementia Prevention

生命全程心血管疾病风险、中年认知轨迹和大脑衰老：对阿尔茨海默病和痴呆症预防的影响

• 批准号: 10171753
• 负责人: Stephen Sidney
• 金额: $ 74.07万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171753
• 关键词: Adult; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Atherosclerosis; Atrophic; Blood Pressure; Blood Vessels; Body mass index; Brain; Cardiovascular Diseases; Carotid Arteries; Clinical; Cognition; Cognitive; Cognitive aging; Coronary Artery Risk Development in Young Adults Study; Data; Dementia; Development; Diabetes Mellitus; Diffusion Magnetic Resonance Imaging; Disease; Disease Marker; Dose; Elderly; Enrollment; Evaluation; Funding; Goals; Health; Hypertension; Impaired cognition; Intervention; Investigation; Lead; Life; Life Cycle Stages; Light; Machine Learning; Magnetic Resonance Imaging; Measures; Obesity; Outcome; Participant; Pathologic; Pattern; Prevention; Prevention strategy; Public Health; Risk; Risk Factors; Science; Statistical Methods; Thick; Time; Time trend; United States National Institutes of Health; Visit; aging brain; black/white disparity; brain health; cardiovascular disorder risk; cognitive change; cognitive function; cognitive testing; cohort; coronary artery calcification; critical period; dementia risk; early life exposure; emerging adult; experience; fasting glucose; heart function; indexing; innovation; middle age; multidisciplinary; neuroimaging; novel; novel strategies; pre-clinical; prevent; racial difference; racial disparity; treatment strategy; trend; white matter; young adult

ABSTRACT Vascular health has emerged as one of the most important determinants of Alzheimer's disease and related dementias. Early adult and midlife cardiovascular disease (CVD) risk factors and subclinical disease may be important drivers of cognitive decline in midlife, a period that most likely is critical for influencing later life dementia risk. Yet, few studies have investigated early adulthood CVD risk exposures, including timing of exposure and whether subthreshold levels impact later life cognition. To accomplish these goals, we propose, to add cognitive testing to the Year 35 visit of the ongoing multisite Coronary Artery Risk Development in Young Adults (CARDIA) study. At baseline, CARDIA enrolled 5,115 black and white participants (mean age 24) who have been carefully followed for 30 years and had cognitive testing at visit years 25 and 30. Cognitive evaluation at Year 35 will allow us to determine 10-year cognitive change (mean age 50 to 60) at a critical time point when cognitive decline starts to diverge and potentially impacts late-life dementia risk. Our specific aims are: 1) To determine, using a life-course approach, the independent associations of 10-year midlife cognitive decline with timing, level (both subthreshold and threshold) and trend in CVD risk factors including body mass index, blood pressure, and fasting glucose, assessed over 35 years from early adult to midlife; 2) To determine the association of 10-year midlife cognitive decline with novel subclinical CVD markers over time including carotid artery intima thickness, coronary artery calcification and cardiac function; 3) To determine whether CVD risk factors and subclinical CVD markers are associated with brain aging indices in midlife, derived by the application of machine-learning neuroimaging pattern analysis to brain MRI and diffusion tensor imaging data obtained on nearly 700 CARDIA participants at midlife; Exploratory) To assess black/white disparities in 10- year cognitive decline and determine the extent to which such disparities are explained by burden of CVD risk. Guided by strong preliminary data, our main hypothesis is that CVD risk factors begin to exert influence as early as the third decade of life and that subthreshold levels (eg systolic blood pressure ≥120 mm) are important drivers for this. In addition, we hypothesize that subclinical CVD measures (especially cardiac function and atherosclerosis) are associated with greater decline in midlife cognition and accelerated brain aging. No other study in the US has such comprehensive data on a wide array of early adult CVD risk factors that may influence cognitive aging. As an experienced multidisciplinary team using innovative statistical methods to analyze essentially unique longitudinal data on early adult and midlife CVD risk factors and subclinical disease, we have the opportunity to investigate the associations of these life-course exposures with cognitive decline and brain health in midlife. Identifying dementia risk factors early in the life-course may lead to interventions to help maintain healthy brain aging and prevent the onset of dementia.

抽象的 血管健康已成为阿尔茨海默氏病和相关的最重要的决定者之一 痴呆症。早期和中年心血管疾病（CVD）的危险因素和亚临床疾病可能是 中年认知能力下降的重要驱动因素，这个时期很可能对以后的生活至关重要 痴呆症风险。然而，很少有研究调查成年早期CVD风险暴露，包括 暴露以及亚阈值水平是否影响以后的生活认知。为了实现这些目标，我们建议， 在35年的访问中添加认知测试 年轻人（Cardia）研究。基线时，卡迪亚（Cardia）招募了5115名黑人和白人参与者（平均年龄） 24）他们经过了30年的仔细跟踪，并在25年和30年进行认知测试。认知 第35年的评估将使我们能够在关键时间确定10年的认知变化（平均年龄50至60岁） 当认知能力下降开始分歧并可能影响后期痴呆症风险时。我们的具体目标 为：1）要使用生活方式方法确定10年中年认知的独立协会 CVD风险因素（包括体重 从成年人到中年，索引，血压和空腹血糖评估了35年； 2）确定 随着时间的流逝，十年中年中年认知能力下降与新型亚临床CVD标记的关联 颈动脉内膜厚度，冠状动脉钙化和心脏功能； 3）确定CVD是否 危险因素和亚临床CVD标记与中年的大脑老化指数有关，由 将机器学习神经影像模式分析应用于大脑MRI和扩散张量成像数据 在中年有近700名Cardia参与者获得；探索性）评估10-的黑/白色分布 认知能力下降，并确定CVD风险的Burnen解释了此类差异的程度。 在强有力的初步数据的指导下，我们的主要假设是CVD风险因素开始在早期发挥影响 由于生命的第三个十年和亚阈值水平（例如收缩压≥120mm）很重要 为此的司机。此外，我们假设亚临床CVD措施（尤其是心脏功能和 动脉粥样硬化）与中年认知和加速脑衰老的下降有关。没有其他 在美国的研究有关于各种早期成人CVD风险因素的全面数据 影响认知衰老。作为一个经验丰富的多学科团队，使用创新的统计方法 分析有关早期和中年CVD风险因素和亚临床疾病的基本独特的纵向数据， 我们有机会调查这些生命过程与认知能力下降的关联 和中年的大脑健康。在生命过程中识别痴呆症危险因素可能会导致干预措施 帮助保持健康的大脑衰老并防止痴呆症的发作。