Hypertensive Disorders of Pregnancy and Subsequent Risk of Vascular Dementia, Alzheimer's Disease, or Related Dementia: A Retrospective Cohort Study Taking into Account Mid-Life Mediating Factors.

项目概要/摘要 这是一份K 01奖的申请书，申请人是公共卫生终身助理教授凯伦·施利普博士。 在犹他州大学。施利普博士正在确立自己作为一个年轻的研究者在妇女的生命历程 流行病学，特别是在一个新的老龄化研究领域，以提高我们对妇女的理解， 阿尔茨海默病（AD）和相关痴呆症（RD）的风险增加，并产生女性特异性 采取干预措施，以减轻风险和改善成果。该奖项将使Schliep博士实现她的目标， 通过提供她的支持，以实现以下培训目标：1）发展 在生物医学信息学和基于人口的研究方法的专业知识; 2）获得经验， 进行临床认知健康评估; 3）提高对影响健康的可改变因素的认识 妇女的中年和晚年认知健康;和4）扩大技能，独立领导和管理一个 成功的研究计划。Schliep博士组建了一个指导团队，其中包括一位主要的导师， 迈克尔瓦尔纳，产科医生和全国知名的母胎医学调查与专业知识， 包括妊娠高血压疾病（HDP）在内的妊娠并发症，以及两位共同导师： 认知神经学家和老年神经学家诺曼·福斯特是痴呆症研究领域公认的领导者， 和Ken Smith博士，一位国际知名的基于人群的分析和遗传/家族的专家， 流行病学Schliep博士有五名顾问，他们在分类建模、ADRD神经心理学、 中年妇女健康、纵向和生存数据分析以及慢性病流行病学。 关于HDP之间的关联知之甚少，估计有2-8%的妊娠并发症， 以及具有相似炎症性血管病因的长期不良母体神经系统结局，包括 ADRD。据估计，目前有540万美国人患有ADRD，其中三分之二是女性。为 美国老龄化人口增加，痴呆症的患病率预计将接近1320万至1600万例， 2050.为什么ADRD对女性的影响不成比例尚不清楚。Schliep博士的研究目标是开发 各种痴呆亚型（包括AD、血管性痴呆、路易体）的分类模型 痴呆和额颞叶痴呆），以分析纵向，个人水平的数据，以更好地了解如何 HDP可能会增加女性患ADRD的风险。Schliep博士将通过以下研究来实现这一目标 目的：1）提高卫生行政数据库中ADRD诊断的准确性; 2）调查 HDP和ADRD之间的关联，以及中年介导因素。提案的预期成果 包括：1）一种在大型关联健康管理系统中准确捕获痴呆症病例的新方法 数据库; 2）HDP如何与特定痴呆亚型联系的清晰度;以及3）技能，经验， Schliep博士的初步数据，以支持未来的研究，确定其他性别特异性风险因素， 痴呆症和中介因素服从干预。

PROJECT SUMMARY/ABSTRACT This is an application for a K01 award for Dr. Karen Schliep, a tenure-line Assistant Professor of Public Health at the University of Utah. Dr. Schliep is establishing herself as a young investigator in women’s life-course epidemiology, specifically in a novel area of aging research—to improve our understanding of women’s increased risk of Alzheimer’s disease (AD) and related dementias (RD) and create women-specific interventions to mitigate risk and improve outcomes. This award will allow Dr. Schliep to achieve her goal of research independence by providing her support to accomplish the following training aims: 1) develop expertise in biomedical informatics and population-based research methods; 2) gain experience in the conduction of clinical cognitive health assessments; 3) enhance knowledge of modifiable factors affecting women’s mid- and late-life cognitive health; and 4) expand skills to independently lead and manage a successful research program. Dr. Schliep has assembled a mentoring team comprising a primary mentor, Dr. Michael Varner, an obstetrician and nationally renowned maternal-fetal medicine investigator with expertise in pregnancy complications including hypertensive disorders of pregnancy (HDP), and two co-mentors: Dr. Norman Foster, a cognitive neurologist and geriatric neurologist and recognized leader in dementia research, and Dr. Ken Smith, an internationally known expert in population-based analyses and genetic/family epidemiology. Dr. Schliep has five advisors with expertise in classification modeling, ADRD neuropsychology, mid-life women’s health, longitudinal and survival data analysis, and chronic disease epidemiology. Little is known regarding the association between HDP, estimated to complicate 2–8% of all pregnancies, and long-term adverse maternal neurological outcomes with similar inflammatory vascular etiologies, including ADRD. An estimated 5.4 million Americans currently suffer from ADRD, two-thirds of whom are women. As the US aging population increases, prevalence of dementia is expected to approach 13.2 to 16.0 million cases by 2050. Why ADRD disproportionately affects women is not known. Dr. Schliep’s research objective is to develop classification models for the various dementia subtypes (including AD, vascular dementia, Lewy body dementia, and frontotemporal dementia) to analyze longitudinal, individual-level data to better understand how HDP may increase a woman’s risk for ADRD. Dr. Schliep will accomplish this through the following research aims: 1) increase accuracy of ADRD diagnoses within health administrative databases; and 2) investigate the association between HDP and ADRD, and mid-life mediating factors. The proposal’s expected outcomes include 1) a novel method to accurately capture dementia cases within large linked health administrative databases; 2) clarity on how HDP may be linked with specific dementia subtypes; and 3) skills, experience, and preliminary data for Dr. Schliep to support future studies identifying other sex-specific risk factors for dementia and mediating factors amenable to interventions.