Advanced Glycation End Products and Alzheimer's Disease

描述（由申请人提供）：Michal Schnaider Beeri是一位心理学家，在老年医学和神经心理学方面具有研究经验。她的长期目标是确定阿尔茨海默病（AD）和认知能力下降的可改变风险和保护因素。特别是心血管疾病和糖尿病的几个风险因素也与AD的发生风险相关。晚期糖基化终末（AGE）产物已被提出作为糖尿病和AD之间关联的解释，并且是本申请中提出的研究项目的重点。该奖项将为Beeri博士提供时间和资源，通过获取以下八个领域的知识和专业知识，为独立科学家的职业生涯做好准备：1）AD的流行病学，2）纵向统计技术，3）心血管危险因素的生理学，4）心血管危险因素的流行病学，5）AGEs，6）最老的老年人，7）鉴别诊断，和8）糖尿病和AGEs的治疗。西奈山医学院是这种培训经验的理想环境。精神病学系对AD进行了广泛的纵向研究，包括由该应用程序的主要导师Jeremy Silverman博士领导的风险因素研究。医学系的糖尿病和老龄化部门，由共同导师Helen Vlassara博士领导，开创了糖尿病AGE研究，并将为大规模AGE提供基础设施。 问题研究本研究旨在探讨AGEs在认知功能减退和AD中的作用 在500名参与一项正在进行的老年人AD心血管危险因素纵向研究的受试者中，受试者的血清和尿液AGEs（甲基乙二醛、N-羧甲基赖氨酸（CML）和低分子量CML）和饮食AGEs将每半年评估一次，持续长达4年，补充其综合认知和心血管评估。 将AGEs确定为可改变的危险因素可能会通过延迟或降低AD和认知能力下降的发病率，在老年人中带来真实的公共卫生收益。

DESCRIPTION (provided by applicant): Michal Schnaider Beeri is a psychologist with research experience in geriatrics and neuropsychology. Her long-term goal is to identify modifiable risk and protective factors for Alzheimer's disease (AD) and cognitive decline. Several risk factors for cardiovascular disease and diabetes in particular, have also been associated with risk for the occurrence of AD. Advanced Glycation End (AGE) products have been proposed as an explanation for the association between diabetes and AD and are the focus of the research project proposed in this application. This award will provide time and resources for Dr. Beeri to prepare for a career as an independent scientist, by acquiring knowledge and expertise in the following eight areas: 1) Epidemiology of AD, 2) Longitudinal statistical techniques, 3) Physiology of cardiovascular risk factors, 4) Epidemiology of cardiovascular risk factors, 5) AGEs, 6) The oldest old, 7) Differential diagnosis, and 8) Treatments for diabetes and AGEs. The Mount Sinai School of Medicine is an ideal environment for this training experience. The Psychiatry Department conducts extensive longitudinal research on AD, including risk factors research led by Dr. Jeremy Silverman, the principal mentor of this application. The Division of Diabetes and Aging of the Department of Medicine, directed by Dr. Helen Vlassara, a co-mentor, has pioneered AGE research in diabetes and will provide the infrastructure for large scale AGE studies. The objective of this project is to examine the role of AGEs in cognitive decline and AD incidence in 500 subjects participating in an ongoing longitudinal cardiovascular risk factors study for AD in the very old. Subjects' serum and urine AGEs (methylglycoxal, N-carboxymethyllysine (CML), and low molecule weight CML) and dietary AGEs will be assessed on a semi annual basis for up to 4 years, complementing their comprehensive cognitive and cardiovascular assessment. Identification of AGEs as a modifiable risk factor may lead to real public health gains among the elderly, by delaying or decreasing incidence of AD and cognitive decline.