Advanced Glycation End Products and Alzheimer's Disease

描述(申请人提供)：Michal Schnaider Beeri是一位在老年病学和神经心理学方面有研究经验的心理学家。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的风险和保护因素。心血管疾病的几个危险因素，特别是糖尿病，也与AD的发生相关。高级糖基化终末(AGE)产品已被提出作为糖尿病和AD之间的关联的解释，并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，通过获得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准备：1)AD流行病学，2)纵向统计技术，3)心血管风险因素生理学，4)心血管风险因素流行病学，5)年龄，6)年龄最大的老年人，7)鉴别诊断，8)糖尿病和AGEs的治疗。西奈山医学院是这种培训体验的理想环境。精神病学系对AD进行广泛的纵向研究，包括这项应用的主要导师Jeremy Silverman博士领导的风险因素研究。医学部糖尿病和老年部由共同导师海伦·弗拉萨拉博士领导，开创了糖尿病年龄研究的先河，并将为大规模老年提供基础设施 学习。该项目的目标是研究年龄在认知功能减退和阿尔茨海默病中的作用 参与一项正在进行的老年AD心血管危险因素纵向研究的500名受试者的发病率。受试者的血清和尿液AGEs(甲基糖醛、N-羧甲基赖氨酸(CML)和低分子CML)以及饮食AGE将每半年评估一次，最长可达4年，作为他们全面认知和心血管评估的补充。将年龄确定为可改变的风险因素可能会通过延缓或减少AD和认知能力下降的发生率，在老年人中带来真正的公共健康收益。

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.