Epidemiology of Glycemia Inflammation & Cognition

这份申请是为KOI指导的研究科学家发展奖，候选人将通过该奖项了解2型糖尿病、血糖紊乱和炎症是如何导致认知能力下降和痴呆的。这项提案的总体目标将是确定血糖和胰岛素水平是否预示着整个葡萄糖耐量范围和不同种族的认知能力下降。此外，炎症的差异是否解释了血糖和认知表现之间的预测联系将被检验。在研究计划内，这一目标将通过进行三项前瞻性研究来实现。具体目标如下： 1)。确定血糖和胰岛素血症的测量与认知功能的关系。 2)。为了确定2型糖尿病与认知的关系，2型糖尿病是血糖和胰岛素血症的标志物，是否受炎症水平的影响，包括C反应蛋白、肿瘤坏死因子α1、白细胞介素6和纤溶酶原激活剂1。 3)。以确定血糖和胰岛素血症的纵向变化与认知损害之间的关系。 4)。确定糖化血红蛋白与2型糖尿病患者发生痴呆症、阿尔茨海默病和血管性痴呆的风险之间的关系。 已经组建了一个由资深调查人员组成的多学科团队，每个人都有不同的专业知识和培训领域，包括糖尿病、神经学和流行病学，以指导候选人拟议的研究和职业发展计划。职业生涯计划的培训部分包括从研究计划中收集的技能以及一系列令人印象深刻的结构化活动，包括糖尿病、炎症和内分泌学方面的正式课程，参加几个关于糖尿病和痴呆症的系列研讨会，与生物统计学家和老年病学家的更多合作，定期指导互动，以及出席/在几个科学会议上发言。这位候选人提出了三项研究，试图获得关于多种族队列中认知障碍的血糖和炎症风险因素的新知识。预期结果应提供新的和 关于血糖控制和血糖紊乱对神经认知功能影响的临床有用信息。拟议的KOI应用程序包括一个极好的研究环境，包括专门针对培训计划目标的资源、一个既定的导师团队以及一个重要的研究问题。导师科学家职业奖的支持将使候选人能够过渡到一名独立的调查人员在 研究领域的血糖和认知，包括建立一个外部资助的研究计划。

This application is for a KOI Mentored Research Scientist Development Award through which the candidate will learn how type 2 diabetes, glucose disorders, arid inflammation contribute to cognitive decline and dementia. The overall goal of this proposal will be to determine whether levels of glycemia and insulinemia are predictive of cognitive decline across the entire range of glucose tolerance and across different ethnic groups. Furthermore, whether differences in inflammation explain predictive associations between glycemia and cognitive performance will be examined. Within the research plan, this goal will be achieved though conducting three prospective studies. The following are the specific aims: 1). To determine the association of measures of glycemia and insulinemia with cognitive functioning. 2). To determine if the association of type 2 diabetes, markers of glycemia and insulinemia, with cognition is mediated by levels of inflammation including c reactive protein, tumor necrosis factor alpha-1, interleukin-6, and plasminogen activator-1. 3). To determine how longitudinal changes in glycemia and insulinemia are associated with cognitive impairment. 4). To determine how glycated hemoglobin is associated with risk of incident dementia, Alzheimer's disease and vascular dementia in patients with Type 2 diabetes. A multidisciplinary team of established senior investigators, each with a different area of expertise and training including diabetes, neurology and epidemiology, has been formed to mentor the candidate on the research and career development plan proposed. The training component of the career plan includes the skills gleaned from the research plan as well as an impressive array of structured activities including formal coursework in diabetes, inflammation and endocrinology, participation in several seminar series on diabetes and dementia, additional collaborations with a biostatistician and geriatrician, regular mentoring interactions; and attendance/presentation at several scientific meetings. The candidate has proposed three studies which seek to gain new knowledge about glycemic and inflammatory risk factors for cognitive impairment in multiethnic cohorts. The expected results should provide new and clinically useful information regarding the influences of glycemic control and glucose disorders on neurocognitive functioning. The proposed KOI application includes an excellent research environment including resources specific to the goals of the training plan, an established team of mentors and, an important research question. The support from the Mentored Scientist Career Award will enable the candidate to make the transition to an independent investigator in the area of glycemia and cognition including establishing an extramurally funded research program.