Dietary Fat Composition, Plasma Lipids, and Cognitive Decline

描述(由申请人提供)：这是一份支持奥利维亚·奥克雷克博士职业发展计划的申请；拟议的项目将有助于她成为认知衰退流行病学的独立研究员。这项研究计划将重点放在与心血管疾病风险密切相关的关键因素-饮食脂肪组成和血脂-与女性健康研究(WHS)老年参与者的认知能力下降之间的关系。此外，为了解决候选人关于饮食脂肪和认知变化之间的机制联系的假设，她提出了在一组参与者中收集两种氧化应激的创新标记物：血浆氧化低密度脂蛋白和荧光氧化产物。首先，奥克雷克博士将研究饱和脂肪和反式不饱和脂肪摄入量的增加是否与五年后认知能力下降的加剧有关。其次，她将评估单不饱和脂肪酸和多不饱和脂肪酸的高摄入量是否与认知能力下降有关；她还将评估鱼类摄入量较高和对地中海饮食的更多坚持是否与认知能力下降较少相关。第三，她将评估血浆低密度脂蛋白和高密度脂蛋白与认知能力下降的关系，以及饮食脂肪和血脂在认知变化路径上的相互作用。最后，她将研究较高水平的新型血浆氧化应激标志物是否与认知能力下降有关，并探索通过氧化应激调节饮食脂肪和认知变化之间的联系。奥克雷克博士将利用从WHS认知研究中收集的前瞻性数据，该研究包括6000多名女性参与者，他们接受了3次重复的认知评估，并将使用现代统计技术对认知变化的混合影响模型进行数据分析。通过解决认知衰退的潜在可改变的风险因素，该项目将为美国老年人提供具有重大公共卫生重要性的信息。这一应用的核心是全面的培训计划。奥克雷克博士将获得关键流行病学研究工具的经验，包括纵向分析、饮食和认知评估以及血液/生物标记物数据收集的方法，所有这些都是在支持性的机构环境中进行的。正式的课程、研究小组会议和个人指导将补充她的学习。总体而言，这项提议将确保奥克雷克博士成为认知功能领域的领先研究人员。

DESCRIPTION (provided by applicant): This is an application to support a career development program for Dr. Olivia Okereke; the proposed project will facilitate her establishment as an independent investigator in the epidemiology of cognitive decline. The research plan will focus on how key factors strongly associated with cardiovascular disease risk - dietary fat composition and plasma lipids - relate to cognitive decline in older participants of the Women's Health Study (WHS). Furthermore, in order to address the candidate's hypotheses regarding mechanistic links between dietary fats and cognitive change, she proposes new collection of two innovative markers of oxidative stress among a subset of participants: plasma oxidized LDL and fluorescent oxidation products. First, Dr. Okereke will examine whether elevated consumption of saturated and trans-unsaturated fats is related to increased cognitive decline over five years of follow-up. Second, she will evaluate whether higher intake of mono- and polyunsaturated fatty acids are associated with decreased cognitive decline; she will also evaluate whether higher fish consumption and greater adherence to Mediterranean diet are associated with less cognitive decline. Third, she will assess the relation of plasma LDL and HDL to cognitive decline, as well as the interactions between dietary fats and plasma lipids on paths of cognitive change. Finally, she will examine whether higher levels of novel plasma markers of oxidative stress are related to increased cognitive decline, and explore mediation by oxidative stress of associations between dietary fat and cognitive change. Dr. Okereke will utilize prospectively collected data from the WHS cognitive study, which includes 6,000+ female participants with 3 repeated cognitive assessments, and will analyze data using modern statistical techniques of mixed-effects models of cognitive change. By addressing potentially modifiable risk factors for cognitive decline, this project will yield information of great public health importance for older Americans. Central to this application is the comprehensive training plan. Dr. Okereke will gain experience with key epidemiologic research tools, including methods for longitudinal analysis, dietary and cognitive assessment, and blood/biomarker data collection, all within a supportive institutional environment. Formal coursework, research group meetings, and individual mentoring will supplement her learning. Overall, this proposal will ensure that Dr. Okereke is poised to become a leading investigator in the area of cognitive function.