EFFECTS OF GLYCOXIDATION ON COGNITION

糖氧化对认知的影响

• 批准号: 7605319
• 负责人: Michal Schnaider Beeri
• 金额: $ 2.13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605319
• 关键词: Advanced Glycosylation End Products; Affect; Age; Aging; Alzheimer' s Disease; Apolipoprotein E; Blood Vessels; Clinical dementia rating scale; Cognition; Computer Retrieval of Information on Scientific Projects Database; Consensus; DNA; Dementia; Diabetes Mellitus; Diagnostic; Diet; Elderly; Environmental Risk Factor; Foundations; Functional disorder; Funding; Future; Genetic; Geriatrics; Grant; Impaired cognition; Inflammatory; Institution; Intake; Intervention; Longitudinal Studies; Oxidative Stress; Participant; Pilot Projects; Prevention; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Source; Study Subject; Time; United States National Institutes of Health; age related; apolipoprotein E-4; cognitive function; diabetes risk; follow-up; glycation; medical schools; neuropsychological; prevent; symposium

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This young investigator pilot project will examine the effects of glycoxidation (advanced glycation end products, AGEs) on cognition in a sample of non-demented elderly participants and lay the foundation for a larger longitudinal study. AGEs have been proposed as an explanation why age and diabetes are risk factors for AD. Nonetheless, AGEs have never been studied prospectively as a risk factor for cognitive decline. Particularly, since they are modifiable by diet, AGEs are very exciting potential candidates for later prevention and treatment studies. The proposed study will build on an ongoing longitudinal study (PI- Dr. Helen Vlassara- Director of the Division of Diabetes and Aging, Department of Geriatrics, at Mount Sinai School of Medicine) examining the age-dependent relationships among circulating AGE and (dietary) AGE intake, markers of oxidative stress, inflammatory markers, and vascular dysfunction in subjects over the age of 60. In the proposed study, subjects will be cognitively assessed by the Clinical Dementia Rating scale, MMSE and the extensive neuropsychological battery of the Alzheimer's Disease Research Center (ADRC) at Mount Sinai, and evaluated by the ADRC consensus diagnostic conference, both at baseline and at follow up. In addition, at baseline, we will collect DNA for APOE and future genetic studies. Findings from this study may identify AGEs as a new modifiable environmental risk factor, acting together with endogenous mechanisms, negatively affecting cognition. This naturalistic cross-sectional and longitudinal study holds the potential to support future interventions to reduce the impact of AGEs, to prevent or delay cognitive decline in the elderly who are at increasing risk of dementia and AD. Hypotheses: 1- Main hypothesis: Subjects with higher levels of AGEs will show poorer cognitive functioning at baseline. 2- Exploratory hypothesis: Subjects with higher baseline AGEs or larger increases in AGEs over time will show a greater degree of cognitive decline. 3- Exploratory hypothesis: APOE4 will intensify the hypothesized relationships in Hypothesis 1.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这个年轻的研究者试点项目将检查糖氧化（晚期糖基化终产物，AGEs）对非痴呆老年参与者样本认知的影响，并为更大规模的纵向研究奠定基础。AGEs已被提出来解释为什么年龄和糖尿病是AD的危险因素。然而，AGEs从未被作为认知能力下降的风险因素进行过前瞻性研究。特别是，由于它们可以通过饮食改变，AGEs是非常令人兴奋的潜在候选人，用于以后的预防和治疗研究。 拟议的研究将建立在一项正在进行的纵向研究（PI-Helen Vlassara博士-西奈山医学院老年病系糖尿病和衰老科主任）的基础上，该研究检查了60岁以上受试者中循环AGE和（饮食）AGE摄入量、氧化应激标志物、炎症标志物和血管功能障碍之间的年龄依赖性关系。 在拟议的研究中，受试者将在基线和随访时通过临床痴呆评定量表、MMSE和西奈山阿尔茨海默病研究中心（ADRC）的广泛神经心理电池进行认知评估，并由ADRC共识诊断会议进行评估。此外，在基线时，我们将收集DNA用于APOE和未来的遗传研究。 这项研究的结果可能会确定AGEs作为一个新的可改变的环境风险因素，与内源性机制一起作用，对认知产生负面影响。这项自然的横断面和纵向研究有可能支持未来的干预措施，以减少AGEs的影响，预防或延迟痴呆和AD风险增加的老年人的认知能力下降。 假设： 1-主要假设：AGEs水平较高的受试者在基线时的认知功能较差。 2-探索性假设：基线AGEs较高或AGEs随时间增加较大的受试者将表现出更大程度的认知下降。 3-探索性假设：APOE 4将强化假设1中的假设关系。