The Role of Lipids in Alzheimer's Disease and Related Dementias among Black Americans: Examining Lifecouse Mechanisms

脂质在美国黑人阿尔茨海默病和相关痴呆中的作用：检查生命机制

基本信息

批准号：
10643344
负责人：
Kristen M George
金额：
$ 12.42万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10643344
关键词：
Address Affect African American population Age Aging Alzheimer disease prevention Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Apolipoprotein E Award Biological Markers Biology Black American Black Populations Black race Brain California Cardiometabolic Disease Cardiovascular Diseases Cardiovascular system Censuses Ceramides Cerebrovascular Trauma Cholesterol Chronic stress Cognitive aging Cohort Studies Data Data Set Dementia Diabetes Mellitus Disparity Dyslipidemias Economics Elderly Epidemiology Equilibrium Ethnic Population Exposure to Funding Genetic Health High Density Lipoprotein Cholesterol High Density Lipoproteins High Prevalence Hippocampus Homeostasis Hypertension Impaired cognition Incidence Infarction Insulin Resistance International LDL Cholesterol Lipoproteins Latino Population Life Cycle Stages Life Experience Link Lipids Literature Low-Density Lipoproteins Magnetic Resonance Imaging Measurement Measures Mediating Mentorship Methods Modeling Modernization Nerve Degeneration Neurodegenerative Disorders Obesity Pathway interactions Physiological Play Positioning Attribute Process Psychometrics Questionnaires Research Research Personnel Risk Factors Role Sphingolipids Stress Structural Racism Testing Time Training Triglycerides United States United States National Institutes of Health Universities White Matter Hyperintensity Work apolipoprotein E-4 brain health cardiometabolism cardiovascular disorder epidemiology cardiovascular disorder risk cohort data harmonization dementia risk disorder risk emerging adult ethnic difference experience genetic risk factor health disparity healthy aging high risk high risk population insight magnetic resonance imaging biomarker metabolomics middle age neuroimaging marker novel psychosocial racial difference racial population racism theories vascular contributions vascular injury

项目摘要

PROJECT SUMMARY/ABSTRACT Black Americans experience a disproportionate burden of cardiovascular disease (CVD) risk factors and Alzheimer's disease and related dementias (ADRD). Studies have identified midlife (~ ages 45-65) dyslipidemia as a risk factor for ADRD. Black Americans have more favorable lipid profiles compared to Whites or Latinos, but their incidence of dyslipidemia in midlife is higher. This seemingly paradoxical relationship between favorable midlife lipid profiles yet high incidence of midlife dyslipidemia and high risk of ADRD among Black Americans has been severely understudied. Lipids play a vital role in neurodegenerative disease, and epidemiologic and metabolomic studies have identified commonly tested lipids (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) as well as sphingolipids (ceramides) as predictors of cognitive aging. Prior work has largely overlooked the contributions of lipids to ADRD risk in Black Americans and few studies have examined the relationship of ceramides with cognitive aging and ADRD in this high-risk group. This project will leverage over 40 years of longitudinal data from two NIH/NIA funded cohort studies, the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study and the Study of Health Aging in African Americans (STAR), to better understand the role of lipids in cognitive aging and ADRD among Black Americans. The scientific objective of this research plan is to characterize the relationship of early adulthood (~ age 30) total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides as well as the novel lipid biomarker, ceramides, with late life cognitive decline, ADRD, and MRI markers of neurodegeneration and vascular brain injury in an all-Black cohort of older adults. The proposed research seeks to: 1) define the role of early adulthood lipids in cognitive aging and ADRD; 2) examine genetic (APOE) and psychosocial (racism) factors as potential effect modifiers; and 3) determine whether the relationship of early adulthood lipid levels with late life cognitive decline and ADRD is partially mediated by midlife (~ ages 45-65) cardiometabolic disease (hypertension, diabetes, obesity, and dyslipidemia). For aging Black Americans with high prevalence of CVD risk factors and at disproportionate risk of dementia, prevention of ADRD has enormous health and economic consequences. This research will be complimented by a detailed training plan based at the University of California, Davis, with guidance from an exceptional mentorship team of nationally and internationally recognized ADRD, lipids, dementia, and cognitive aging researchers. The training will build upon the applicant's background in CVD and dementia epidemiology by incorporating specialized training in lifecourse theory and modern causal inference methods, biology of lipids, psychometric testing, and measurement and modeling of neuroimaging biomarkers. The combined research and training will prepare the applicant to successfully transition to an independent researcher of disparities in vascular contributions to ADRD.

项目概要/摘要美国黑人承受着不成比例的心血管疾病 (CVD) 危险因素负担阿尔茨海默病和相关痴呆症（ADRD）。研究已确定中年（~ 45-65 岁）血脂异常是 ADRD 的危险因素。与白人相比，美国黑人的血脂状况更有利或拉丁裔，但他们中年血脂异常的发生率更高。这种看似矛盾的关系中年血脂状况良好但中年血脂异常发生率高以及 ADRD 风险高美国黑人的研究严重不足。脂质在神经退行性疾病中起着至关重要的作用，流行病学和代谢组学研究已经确定了常用的测试脂质（总胆固醇、HDL 胆固醇、低密度脂蛋白胆固醇和甘油三酯）以及鞘脂（神经酰胺）作为认知的预测因子老化。先前的工作在很大程度上忽视了脂质对美国黑人 ADRD 风险的贡献，并且很少有人这样做。研究调查了神经酰胺与这一高危人群的认知衰老和 ADRD 的关系。该项目将利用 NIH/NIA 资助的两项队列研究 40 多年的纵向数据，即 Kaiser 健康老龄化和多样化生活经历（KHANDLE）研究和非洲健康老龄化研究美国人 (STAR)，更好地了解脂质在黑人认知衰老和 ADRD 中的作用美国人。该研究计划的科学目标是描述成年早期的关系（~ 30 岁）总胆固醇、HDL 胆固醇、LDL 胆固醇、甘油三酯以及新型脂质生物标志物、神经酰胺、晚年认知能力下降、ADRD 和神经退行性疾病的 MRI 标志物全黑人老年人群中的血管性脑损伤。拟议的研究旨在：1）定义认知衰老和 ADRD 中的成年早期脂质； 2）检查遗传（APOE）和社会心理（种族主义）作为潜在影响调节因素的因素； 3) 确定成年早期血脂水平是否与晚年认知能力下降，ADRD 部分由中年（~ 45-65 岁）心脏代谢介导疾病（高血压、糖尿病、肥胖症和血脂异常）。对于患病率较高的老龄化美国黑人 CVD 危险因素和痴呆风险不成比例，预防 ADRD 具有巨大的健康和经济后果。这项研究将得到基于以下基础的详细培训计划的补充：加州大学戴维斯分校，在来自国内外的优秀导师团队的指导下国际公认的 ADRD、血脂、痴呆和认知衰老研究人员。培训将建立在通过结合专业培训，申请人在心血管疾病和痴呆症流行病学方面的背景生命历程理论和现代因果推理方法、脂质生物学、心理测试和神经影像生物标志物的测量和建模。研究和培训相结合将为申请人成功转型为血管贡献差异的独立研究员 ADRD。